MedWorm provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest medical blog items that have been tagged with 'drug development'. Sat, 03 Sep 2011 02:09:02 +0100 http://www.medworm.com/index.php?rid=5182292&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F09%2F01%2Fglaxosmithkline_reviews_the_troops.php Several readers sent along this article from the Times of London (via the Ottawa Citizen) on GlaxoSmithKline's current research setup. You can tell that the company is trying to get press for this effort, because otherwise these are the sorts of internal arrangements that would never be in the newspapers. (The direct quotes from the various people in the article are also a clear sign that GSK wants the publicity). The piece details the three-year cycle of the company's Drug Performance Units (DPUs), which have to come and justify their existence at those intervals. We're just now hitting the first three-year review, and as the article says, not all the DPUs are expected to make it through: In 2008, the company organized its scientists into small teams, some with just a handful of staff, ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=5182292 Thu, 01 Sep 2011 11:35:15 +0100 5182292 http://www.medworm.com/index.php?rid=5078011&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F07%2F29%2F2011_drug_approvals_are_up_we_rule_right.php I've been meaning to comment on this article from the Wall Street Journal - the authors take a look at the drug approval numbers so far this year, and speculate that the industry is turning around. Well, put me in the "not so fast" category. And I have plenty of company there. Neither Bruce Booth (from the venture capital end), John LaMattina (ex-Pfizer R&D head) nor Matthew Herper at Forbes are buying it either. One of the biggest problems with the WSJ thesis is that most of these drugs have been in development for longer than the authors seem to think. Bruce Booth's post goes over this in detail, and he's surely correct that these drugs were basically all born in the 1990s. Nothing that's changed in the research labs in the last 5 to 10 years is likely to have significantly affected th... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=5078011 Fri, 29 Jul 2011 11:47:18 +0100 5078011 http://www.medworm.com/index.php?rid=5008637&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F07%2F02%2Finnovation_and_return_europe_vs_the_us.php Here's another look at the productivity problems in drug R&D. The authors are looking at attrition rates, development timelines, targets and therapeutic areas, and trying to find some trends to explain (or at least illuminate) what's been going on. Their take? Attrition rates have been rising at all phases of drug development, and most steeply in Phase III. (This sounds right to me). Here are their charts: And when they look at where the drug R&D efforts have been going, they find that comparatively more time and money has been spent on targets with lower probability of success. That means (among other things) more oncology, Alzheimer's, arthritis, Parkinson's et al. and less cardiovascular and anti-HIV. That makes sense, too, in a paradoxical way. If we were to get drugs in those areas... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=5008637 Sat, 02 Jul 2011 15:07:33 +0100 5008637 http://www.medworm.com/index.php?rid=4968905&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2FkCs8X6zlPB8%2F Earlier this week, Medco Health Solutions, the big pharmacy benefits manager, struck an unusual deal with Sanofi to help the drugmaker navigate the path from laboratory to formulary placement. Specifically, Medco will provide input on clinical trial design, help develop comparative effectiveness data and review usage of existing medications to improve patient adherence. The move reflects a growing awareness among drugmakers that designing and testing a compound for FDA approval is no longer the only key hurdle to winning sales and market share. We spoke with Robert Epstein, Medco’s clinical research and development officer, about the deal… Pharmalot: You’re saying this is the first deal of this sort. But the problems you hope to address aren’t new, right? Epstein: It’s been very ... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=4968905 Fri, 24 Jun 2011 17:25:12 +0100 4968905 http://www.medworm.com/index.php?rid=4872431&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F05%2F26%2Fpfizers_brave_new_medchem_world.php OK, here's how I understand the way that medicinal chemistry now works at Pfizer. This system has been coming on for quite a while now, and I don't know if it's been fully rolled out in every therapeutic area yet, but this seems to be The Future According to Groton: Most compounds, and most actual chemistry bench work, is apparently going to be done at WuXi (or perhaps other contract houses?) Back here in the US, there will be a small group of experienced medicinal chemists at the bench, who will presumably be doing the stuff that can't be easily shipped out (time-critical, difficult chemistry, perhaps even IP-critical stuff, one wonders?) But these people are not, as far as I can tell, supposed to have ideas of their own. No, ideas are for the Drug Designers, which is where the rest of ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=4872431 Thu, 26 May 2011 12:24:03 +0100 4872431 http://www.medworm.com/index.php?rid=4744930&cid=t_105099_150_f&fid=34889&url=http%3A%2F%2Fpharmamkting.blogspot.com%2F2011%2F04%2Fnew-estimate-of-drug-development-cost.html I have tackled the estimated $800 million drug develop cost gorilla before and garnered a lot of comments from readers, including Dr. Joseph DiMasi, whose team came up with that number way back in 2003. Since then, the number has been adjusted upward to over $1 Billion due to inflation/increased costs. In his comments to me -- see "Tufts Hangs Tough on Opportunity Cost Analysis" -- DiMasi said "You write that [my] study is disputed. That's true, but, as far as I can see, the ultimate sources of that criticism are those with obvious political agendas and who lack appropriate expertise. I have never seen a criticism of the methodology from a bona fide economist."Now comes a NEW estimate from someone who HAS the appropriate expertise, if by "appropriate" DiMasi meant someone who has has a PhD... Pharma Marketing Blog blogs http://www.medworm.com/rss/comments.php?id=4744930 Sat, 23 Apr 2011 18:34:00 +0100 4744930 http://www.medworm.com/index.php?rid=4676779&cid=t_105099_87_f&fid=38368&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FDisruptiveWomenInHealthCare%2F%7E3%2FQjV-tryLFQ4%2F By Glenna Crooks. Having been engaged in rare disease research and orphan drug development for many decades and as one who continues behind-the-scenes to encourage the work, events of the last few weeks about Makena’s launch sent chills through me.  The firestorm that followed created some heat but none sufficient to help relieve the shivers. Others might declare the outcome a “win” but the more I read, the worse it seems. I’m not privy to what really happened, only what the press reports. It does not look good… for virtually anyone of the players involved, especially the critics.  Those critics raised tough questions and to date only the company has faced them. It’s about time the critics themselves –and perhaps others as well – face some.    For those who’ve mi... Disruptive Women in Health Care blogs http://www.medworm.com/rss/comments.php?id=4676779 Mon, 04 Apr 2011 09:31:25 +0100 4676779 http://www.medworm.com/index.php?rid=4560579&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F03%2F08%2Fthat_43_million_rd_figure.php One of the readers in the comments section to the last post noticed Rebecca Warburton trying to clarify that absurd $43-million-per-drug R&D figure. You'll find her response in the comments section to the Slate piece that brought this whole study so much attention. Says Warburton: . . .Our estimate of $59 million is the median development (the “D” in R&D) cost per average drug, not just NMEs (new chemicals) and does not include basic research costs, for which there is no reasonable estimate available. But that explanation won't wash, as some of the readers over at Slate noticed as well. If you read the Light and Warburton article itself, you find the authors talking about nothing but "R&D" all the way through. In the one section where they do start to make a distinction, they brush a... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=4560579 Tue, 08 Mar 2011 12:26:31 +0100 4560579 http://www.medworm.com/index.php?rid=4560580&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F03%2F07%2Fthe_costs_of_drug_research_beginning_a_rebuttal.php Note: a follow-up post to this one can be found here. I've had a deluge of emails asking me about this article from Slate on the costs of drug research. It's based on this recent publication from Donald Light and Rebecca Warburton in the London School of Economics journal Biosocieties, and it's well worth discussing. But let's get a few things out of the way first. The paper is a case for the prosecution, not a dispassionate analysis. The authors have a great deal of contempt for the pharmaceutical industry, and are unwilling (or unable) to keep it from seeping into their prose. I'm tempted to reply in kind, but I'm supposed to be the scientist in this discussion. We'll see how well I manage. Another thing to mention immediately is that this paper is, in fact, not at all worthless. In b... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=4560580 Mon, 07 Mar 2011 12:54:34 +0100 4560580 http://www.medworm.com/index.php?rid=4482968&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2FwL9iyIedicI%2F The drug development race is pockmarked with efforts to discover and market a first-in-class treatment. Of course, not everyone can be first, which means there are likely to be other meds that become available. This has become known as the ‘me too’ syndrome, in which one drugmaker after another tries to develop a med similar to a big seller and grab a piece of the business. This approach, however, has been skewered for failing to yield needed innovations and using resources - at companies and at the FDA - that might be put to better use. So how can this be modified in a way that would realign priorities and generate better outcomes and returns for all considered? An essay in the Journal of the American Medical Association suggests an alternative approach - require me-too meds ... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=4482968 Wed, 16 Feb 2011 16:06:19 +0100 4482968 http://www.medworm.com/index.php?rid=4464691&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F02%2F11%2Fdrug_problems_a_diagnosis.php There's no shortage of "What's Wrong With the Drug Industry" article these days. I wanted to call attention to another one that's just appeared in JPET. I don't agree with all of it, but it does make some important points. If I had to give a one-line summary of its thesis, it would be "Drug discovery forgot pharmacology and lost its way". The author, Michael Williams of Northwestern (and of 35 years at Merck, Novartis, Abbott, and Cephalon) is a pharmacologist himself, and feels that the genomics era (and indeed, the whole target-driven molecular biology era) has a lot to answer for. He also thinks that people have become seduced by technology: Rather than creating synergies by using multiple complementary technologies to find answers to discrete questions in a focused and coherent manne... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=4464691 Fri, 11 Feb 2011 14:11:48 +0100 4464691 http://www.medworm.com/index.php?rid=4436938&cid=t_105099_150_f&fid=34889&url=http%3A%2F%2Fpharmamkting.blogspot.com%2F2011%2F02%2Fshould-fda-have-approved-contrave-for.html As reported in the WSJ Health Blog, FDA said it wouldn’t consider approving the experimental weight-loss drug Contrave without another clinical trial. FDA's decision comes after an FDA advisory panel voted in December to recommend approval of the drug.Many pundits consider this another example of how risk-averse the FDA has become and how its decisions are hampering innovation. Even critics of the drug industry like Dr. Carlat claim that FDA's Contrave decision was a "Big Mistake" (see here).Why does Carlat think it was a mistake when Contrave "is simply a combination" of two generics -- burpropion (Wellbutrin) and naltrexone -- that have been available for a long time? He says "Combining Wellbutrin and naltrexone was not something the average doctor would have ever thought of for an obe... Pharma Marketing Blog blogs http://www.medworm.com/rss/comments.php?id=4436938 Fri, 04 Feb 2011 13:46:00 +0100 4436938 http://www.medworm.com/index.php?rid=4424444&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2F878kSFkTBos%2F The pursuit of orphan drugs remains high and why not? The Orphan Drug Act, which encourages development of meds for diseases with small markets, gives drugmakers seven years in which to sell a product without competition for seven years and sometimes tax incentives, too. So it is not surprising that a record 323 requests for designation were submitted to the FDA last year. And the agency’s Office of Orphan Products Development obliged by designating 192 meds with orphan status. As a result, there are now 2,308 drugs with this designation, as noted by the FDA Law Blog, which scanned the FDA orphan drug database. However, the FDA approved only 14 orphan meds last year, down from 17 approvals in 2009 and down from a high of 25 back in 1996. Why is there so much interest lately? Hard to ... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=4424444 Tue, 01 Feb 2011 14:26:56 +0100 4424444 http://www.medworm.com/index.php?rid=4394747&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2FOXP2WERs2zc%2F Concerned about the slow pace at which new treatments are being developed by big pharma, the National Institutes of Health is planning to open a new drug development center by October. The move, which comes after months of planning and study, would collect more than $700 million in projects already under way at various NIH institutes. The decision reflects growing concern that the pharmaceutical industry is finding it difficult to deliver on new breakthroughs while, at the same time, continuing to pare some research efforts in hopes of saving money. Nearly every big drugmaker faces a revenue squeeze as big sellers face generic competition and are reacting by eliminating numerous projects to juice their bottom lines. Big pharma productivity has been declining for 15 years “and it certainl... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=4394747 Mon, 24 Jan 2011 17:22:45 +0100 4394747 http://www.medworm.com/index.php?rid=4382939&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F01%2F21%2Foh_and_while_youre_at_it_.php Well, this is a question that (I must admit) had not crossed my mind. Courtesy of Slate, though, we can now ask how we can make pharmaceuticals more environmentally friendly. No, not the manufacturing processes: this article's worried about the drugs that are excreted into the water supply. It's worth keeping an eye on this issue, but I haven't been able, so far, to get very worked up about it. It's true that there have been many studies that show detectable amounts of prescription drugs in the waste water stream. The possible environmental effects mentioned in the article, though, are seen at much higher concentrations. I think that much of the attention given to this issue comes from the power of modern analytical techniques -if you look for things at parts-per-billion level (or below),... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=4382939 Fri, 21 Jan 2011 12:51:45 +0100 4382939 http://www.medworm.com/index.php?rid=4338251&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2011%2F01%2F12%2Fgassing_your_crystals.php Now, this is a pretty neat trick. One of the things that drug development people have to worry about a lot is the crystal forms of the new compound. You might imagine (if you haven't had to do this stuff) that if a compound is crystalline, then that's that - you've got the solid form now, and full speed ahead. But many substances can crystallize in all sorts of forms - here's one with at least seven different solved crystal structures (and it has more that haven't yielded an X-ray structure yet). By the time you bring in solvates, where the molecule crystallizes along with the solvent it was last in, or with water dragged in from the air, or what have you, you can go well up into the double digits, and we haven't even begun talking about salt forms yet. Each one of those starts the whole ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=4338251 Wed, 12 Jan 2011 16:18:51 +0100 4338251 http://www.medworm.com/index.php?rid=3976695&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2010%2F09%2F16%2Fsix_sigma_in_drug_discovery_part_one_are_chemists_too_individual.php I had an interesting email about a 2009 paper in Drug Discovery Today that has some bearing on the "how much compound to submit" question, as well as several other areas. It's from a team at AstraZeneca, and covers their application of "Lean Six Sigma" to the drug discovery process. I didn't see it at the time, but The title probably made me skip over it even if I had. I'll admit my biases up front: outside of its possible uses in sheer widget-production-line settings, I've tended to regard Six Sigma and its variants as a buzzword-driven cult. From what I've been able to see of it, it generates a huge number of meetings and exhortations from management, along with a blizzard of posters, slogans, and other detritus. On the other hand, it gives everyone responsible a feeling that they've Re... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=3976695 Thu, 16 Sep 2010 13:44:17 +0100 3976695 http://www.medworm.com/index.php?rid=3695802&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2010%2F06%2F24%2Ffungal_structures_to_the_rescue.php From the Wall Street Journal, here's the history of the Novartis compound fingolimod, from its intellectual origins as a cicada fungus extract to today, when it might become the first oral medication for multiple sclerosis. If fingolimod makes it, it'll also be the first drug I'm aware of that has a flippin' n-octyl chain hanging off it - a flagrant violation of everything that a medicinal chemist learns in their first month on the job. Hydrophobic bulk, metabolism bait, entropic penalty - well, there it is. I'm not suggesting that we all go out and slap pennzoilane and crico-cene side chains on our lead drug candidates, but it's worth remembering that the race is not always to the swift, nor the battle to the strong. (Source: In the Pipeline) In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=3695802 Thu, 24 Jun 2010 16:08:02 +0100 3695802 http://www.medworm.com/index.php?rid=3599655&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2FQ92zydQWQCo%2F I think that we need as many different sets of eyes looking at our problems as we can get. The more shots get taken, from all sorts of angles, the better the chance of hitting something. And a huge company, while it does have room for some differences inside it, tends to homogenize viewpoints. The One Big Project with its One Big Compound will get the resources for a given area in the end. It’s like when a multiplex theater opens in a smaller town – they tell everyone that with 16 screens they’ll be able to bring in movies that otherwise never would play there. But come July, all sixteen screens are probably showing Revenge of the MegaSequel Part II, just to make sure that one’s starting every twenty minutes. These words come via Derek Lowe. Writing about a deal bet... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=3599655 Wed, 26 May 2010 06:49:11 +0100 3599655 http://www.medworm.com/index.php?rid=3590451&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2F7ONJcvGV7L0%2F Image by Giuli-O via Flickr Malaria is a disease that is close to home, since I’ve had it a couple of times (and it is not fun). It’s also the kind of disease that doesn’t get the attention of the media or pharma companies out in the west, or at least that seems to be the case. Well not this past week, a week that saw GSK release a dataset containing the structures and screening data for over 13,500 compounds confirmed to inhibit parasite growth by more than 80% at 2 uM concentration. The GSK data is one of three datasets released into the ChEMBL Neglected Tropical Diseases archive joining data from Novartis and St. Jude. The GSK data however is the only one that has been made available under the CC0 license and is the second example of data that came from pharma being... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=3590451 Sun, 23 May 2010 03:48:49 +0100 3590451 http://www.medworm.com/index.php?rid=3560496&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2Fas95V6glgzI%2F Containing drug development costs and speeding compounds through the pipeline is always a big issue, but clinical trials are becoming more expensive anyway. Why? One answer is the increasing complexity of the studies - the number of procedures for each clinical trial rose 49 percent from the 2000 to 2003 period to the 2004 to 2007 timeframe, and the total effort per protocal jumped 54 percent. For instance, the average number of eligibility criteria used to screen volunteers rose 58 percent, which contributed to a 21 percent decline in volunteers enrolling in trials. But the larger number of procedures per protocol dissuades volunteers from completing trials - retention rates dropped 230 percent, according to the Tufts Centers for the Study of Drug Development, which reviewed data from 8,... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=3560496 Thu, 13 May 2010 15:15:35 +0100 3560496 http://www.medworm.com/index.php?rid=3552479&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2F3fXFN7LeCBI%2F Image by zh1yong via Flickr $10 million. Yes, that’s the amount of money that a certain Bill Gates has invested in Schrödinger via his private investment company. As Derek Lowe notes in his excellent Nature News article, Schrödinger is no stranger to billionaire benefactors, having enjoyed a long relationship with D. E. Shaw (someone I really admire and envy), but that relationship has been as much about science as anything else (as evidenced by Desmond). The first thing that makes this interesting is the size of the investment (according to Lowe revenues are estimated at $20 million, which sounds about right), but what I am really interested in is what the investment might be used for. Lowe speculates that one possible project would be “to collaborate with industrial dru... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=3552479 Tue, 11 May 2010 05:20:29 +0100 3552479 http://www.medworm.com/index.php?rid=3378732&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2Fj_XwUiio9VA%2F The move is designed to jumpstart testing and approval of new regimens for so-called drug cocktails to combat tuberculosis, AIDS and cancer. The guidelines would apply only to drugs for life-threatening illnesses for which options don’t already exist, and that drug cocktails are believed necessary. Among those involved: the Critical Path to TB Regimens, which includes Pfizer, Sanofi-Aventis, AstraZeneca, GlaxoSmithKline and a unit of Johnson & Johnson; Global Alliance for TB Drug Development, the Critical Path Institute and Treatment Action Group, as well as the Bill & Melinda Gates Foundation. The companies have agreed to share data and test combo treatments. “This represents a bigger issue - the strengthening of regulatory science” to encompass scientific advances,... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=3378732 Thu, 18 Mar 2010 11:10:42 +0100 3378732 http://www.medworm.com/index.php?rid=3322506&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2010%2F03%2Fneuropsychology-abstract-of-day.html Today's recommended article to read; abstract from PubMed:Bergmans BA & De Strooper B. gamma-secretases: From cell biology to therapeutic strategies. Lancet Neurology. 2010 Feb; 9(2 ): 215-226.Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium; Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.Presenilins form the catalytic part of the gamma-secretases, protein complexes that are responsible for the intramembranous cleavage of transmembrane proteins. The presenilins are involved in several biological functions, but are best known for their role in the generation of the beta-amyloid (Abeta) peptide in Alzheimer's disease and are therefore thought to be important drug targets for this disorder. Mutations in the presenilin genes cause early-onset... BrainBlog blogs http://www.medworm.com/rss/comments.php?id=3322506 Tue, 02 Mar 2010 15:03:00 +0100 3322506 http://www.medworm.com/index.php?rid=3290893&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2010%2F02%2Fneurodegenerative-disease-drug.html From Fierce Biotech:UCSF enters drug discovery agreement with GenentechPosted February 19, 2010"The University of California, San Francisco has signed a partnership agreement with Genentech, Inc., a wholly owned member of the Roche Group, to discover and develop drug candidates for neurodegenerative diseases."Through the agreement, Genentech will provide funding and its research acumen in neuroscience and will collaborate with UCSF to identify small molecules."Read the full article (Source: BrainBlog) BrainBlog blogs http://www.medworm.com/rss/comments.php?id=3290893 Sat, 20 Feb 2010 09:24:00 +0100 3290893 http://www.medworm.com/index.php?rid=3079569&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F12%2F10%2Fpfizers_rd_productivity.php Courtesy of Bernard Munos, author of the Nature Reviews article that I began blogging about yesterday, comes this note about Pfizer's track record with new molecules. His list of Pfizer NMEs since 2000 is Geodon (ziprasidone, 2001), Vfend (voriconazole, 2002, from Vicuron - whoops, not so, this one's Pfizer's), Relpax (eletriptan, 2002), Somavert (pegvisomant, 2003, from Pharmacia & Upjohn), Lyrica (pregabalin, 2004, from Warner Lambert), Sutent (sunitinib, 2006, from Sugen/Pharmacia), Chantix (varenicline, 2006), Selzentry (maraviroc, 2007), and Toviaz (fesoterodine, 2008, from Schwarz Pharma). There are some good drugs on that list, but considering that even just five years ago, the company was claiming that it had 101 NMEs in development, and was going to file 20 NDAs by now, it might s... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=3079569 Thu, 10 Dec 2009 17:13:39 +0100 3079569 http://www.medworm.com/index.php?rid=3075756&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F12%2F10%2Fselective_scaffolds.php We spend a lot of time in this business talking about molecular scaffolds - separate chemical cores that we elaborate into more advanced compounds. And there's no doubt that such things exist, but is part of the reason they exist just an outcome of the way chemical research is done? Some analysis in the past has suggested that chemical types get explored in a success-breeds-success fashion, so that the (over)representation of some scaffold might not mean that it has unique properties. It's just that it's done what's been asked of it, so people have stuck with it. A new paper in J. Med. Chem. from a group in Bonn takes another look at this question. They're trying to see if the so-called "privileged substructures" really exist: chemotypes that have special selectivity for certain target cl... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=3075756 Thu, 10 Dec 2009 13:40:12 +0100 3075756 http://www.medworm.com/index.php?rid=3037087&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F11%2F28%2Frecommended_books_for_medicinal_chemists_part_one.php I asked recently for suggestions on the best books on med-chem topics, and a lot of good ideas came in via the comments and e-mail. Going over the list, the most recommended seem to be the following: For general medicinal chemistry, you have Bob Rydzewski's Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research. Many votes also were cast for Camille Wermuth's The Practice of Medicinal Chemistry. For getting up to speed, several readers recommend Graham Patrick's An Introduction to Medicinal Chemistry. And an older text that has some fans is Richard Silverman's The Organic Chemistry of Drug Design and Drug Action. Process chemistry is its own world with its own issues. Recommended texts here are Practical Process Research & Development by Neal Anderson and Pro... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=3037087 Sat, 28 Nov 2009 17:02:25 +0100 3037087 http://www.medworm.com/index.php?rid=2996031&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2FPharmalot%2F%7E3%2FsJ4DaAFJfbQ%2F Hello, everyone. In between raking leaves, hanging with the short people and walking our faithful friend, we thought it might be helpful to offer you a few minutes of interesting reading. As always, there is much to track. Just the same, we have some errands to run shortly - what the weekend be without running from store to store? So we’ll leave you with these items for now and resume the usual routine tomorrow. Hope your weekend is going well and you enjoy yourselves…. MIT has a new project called New Drug Development Paradigms that includes drugmakers and federal health agencies, which hope to overcomes the bottlenecks in drug development, according to The New York Times. The hope is to create new ‘prediction models,’ share info about the biology of diseases and e... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=2996031 Sun, 15 Nov 2009 19:21:35 +0100 2996031 http://www.medworm.com/index.php?rid=2890856&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2FlleAz5rc2Pw%2F A few days ago, via the typical following of links that is typical of a good search and browse section on the interwebs, I chanced upon a discussion about a presentation given by Justin Gehtland at RailsConf. The talk was entitled Small Things, Loosely Joined, Written Fast and that title has been stuck in my head ever since. Funnily enough, what was in my head was not software, and web architectures, cause today, I consider that particular approach almost essential to building good applications and scalable infrastructures, and most people in the community seem to understand that (not sure about scientific programmers though). What I started thinking about was if that particular philosophy could be extended to the biopharma industry. Without making direct analogies, but without suspending... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=2890856 Wed, 14 Oct 2009 06:29:04 +0100 2890856 http://www.medworm.com/index.php?rid=2838718&cid=t_105099_77_f&fid=37259&url=http%3A%2F%2Fwww.horizonpress.com%2Fblogger%2F2009%2F09%2Fapplications-of-metagenomics-to.html Recent progress in mining the rich genetic resource of non-culturable microbes has led to the discovery of new genes, enzymes, and natural products. The impact of metagenomics is witnessed in the development of commodity and fine chemicals, agrochemicals and pharmaceuticals where the benefit of enzyme-catalyzed chiral synthesis is increasingly recognized. Recovery of metabolic pathways and gene clusters involved in biosynthesis of antibiotics and bioactive molecules has increased the prospect of identifying useful natural and synthetic products for drug development. The discovery of biocatalysts operating optimally with high efficiency in conditions amenable to industrial processes requirements are key to successful development of food products, detergent additives, bioactive compounds, fu... Microbiology Blog: The weblog for microbiologists. blogs http://www.medworm.com/rss/comments.php?id=2838718 Mon, 28 Sep 2009 13:59:00 +0100 2838718 http://www.medworm.com/index.php?rid=2828339&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2009%2F09%2Fupcoming-event-genesis-conference-2009.html The Genesis 2009 Conference will take place on the 10th and 11th of December at the Queen Elizabeth II Conference Centre (London).From the website:"Welcome to Genesis 2009 – “Back in focus!”The challenges of the economic downturn stimulated us to build innovative new partnerships at Genesis last year. The resultant exciting mix of business and science is something many have only dreamed of. This will be retained for 2009 with a streamlined approach for delegates to maximise the return on your investment in participating."For details, please see the conference website (Source: BrainBlog) BrainBlog blogs http://www.medworm.com/rss/comments.php?id=2828339 Thu, 24 Sep 2009 13:20:00 +0100 2828339 http://www.medworm.com/index.php?rid=2804077&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2009%2F09%2Fbusiness-world-biotechnology-venture.html From The New York Times:Biotech Tries to Shrug Off SetbacksBy JAMES FLANIGANPublished: September 17, 2009"While some investors are pulling back, life sciences companies continue to innovate, and hope the capital to expand will come."Read the piece (Source: BrainBlog) BrainBlog blogs http://www.medworm.com/rss/comments.php?id=2804077 Thu, 17 Sep 2009 14:36:00 +0100 2804077 http://www.medworm.com/index.php?rid=2793284&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2009%2F09%2Fworld-alzheimers-day-21st-september.html World Alzheimer's Day (Source: BrainBlog) BrainBlog blogs http://www.medworm.com/rss/comments.php?id=2793284 Mon, 14 Sep 2009 14:26:00 +0100 2793284 http://www.medworm.com/index.php?rid=2786158&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2009%2F09%2Fupcoming-eventalzheimers-drug-discovery.html The 10th international conference on Alzheimer's disease drug discovery takes place next week on the 14th and 15th in Jersey City, NJ.From the conference website:"The 10th International Conference on Alzheimer's Disease Drug Discovery is presented by the Alzheimer's Drug Discovery Foundation (ADDF), the only public charity solely dedicated to rapidly accelerating the discovery and development of drugs to prevent, treat and cure Alzheimer's disease and cognitive aging.This conference brings together academic and industry scientists to accelerate the development of novel drug discovery programs for Alzheimer’s disease and related dementias."Visit the conference website (Source: BrainBlog) BrainBlog blogs http://www.medworm.com/rss/comments.php?id=2786158 Thu, 10 Sep 2009 23:27:00 +0100 2786158 http://www.medworm.com/index.php?rid=2734154&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2009%2F08%2Fdrug-development-in-neurodegenerative.html Available at BMC NeurologyProceedings of the 2009 Drug Discovery for Neurodegeneration ConferenceProceedings from Drug Discovery for Neurodegeneration ConferenceWashington, DC, USA. 2–3 February 2009Edited by Diana W Shineman and Howard M FillitBMC NeurologyContents of Volume 9 Suppl 1Click here for open access to contents of this issue (Source: BrainBlog) BrainBlog blogs http://www.medworm.com/rss/comments.php?id=2734154 Wed, 26 Aug 2009 10:11:00 +0100 2734154 http://www.medworm.com/index.php?rid=2734192&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2FJcARmntqasQ%2F Image via Wikipedia People outside the pharma industry rarely realize how difficult a task the drug discovery process is. But perhaps, even among scientists, there is a significant lack of knowledge of the complexities of the drug development process. Part of the reason is that this process happens behind the closed walls of pharma and is rarely published, but it’s also not the sexy part of bringing a therapeutic to market. Derek Lowe’s post on a patent dispute between Novartis and the Government of India speaks to this complexity (in this case polymorphs). The comments are very interesting too as he asks for examples of drugs where getting a particular polymorph was essential to getting proper efficacy. The whole process of bringing a drug to life involves everything from b... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=2734192 Tue, 25 Aug 2009 23:12:37 +0100 2734192 http://www.medworm.com/index.php?rid=2702509&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F08%2F14%2Fspraypainted_for_success.php I do a lot of talking around here about how the general public doesn't really have a good idea of what goes on inside a drug company. But a conversation with a colleague has put me to thinking that this might be largely our own fault. Consider the public face that our industry projects. Look at the press releases and the advertisements - what's the impression that you get? That there is a defined process for discovering drugs, for one thing, and what's more, that we are the master of it. Now, I know that we don't always send out that message. There are attempts to tell people about how many compounds have to be made, how many projects end up failing. But for the most part, we don't press-release that stuff. No, the press releases are for the investors, and for them, we want to project th... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2702509 Fri, 14 Aug 2009 12:48:47 +0100 2702509 http://www.medworm.com/index.php?rid=2699735&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2009%2F08%2Fc-span-3-airing-alzheimers-disease.html C-SPAN-3 is currently airing an earlier session by the subcommittee on aging on the topic of Alzheimer's Disease. All C-SPAN channels can be streamed online.Information about the program can be found here. (Source: BrainBlog) BrainBlog blogs http://www.medworm.com/rss/comments.php?id=2699735 Thu, 13 Aug 2009 19:07:00 +0100 2699735 http://www.medworm.com/index.php?rid=2688906&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F08%2F10%2Fpharmas_return_on_investment_yikes.php There's a recent article in Nature Reviews Drug Discovery that has some alarming figures in it. This is yet another look at the industry from McKinsey, and we'll get to their McKinseyish solutions in a moment. But first, some numbers: They calculate that the return on investment (ROI) from small-molecule drug research was nearly 12% during the late 1990s, but since 2001 it's been more like 7.5%. If true, that's not a very nice number at all, because their data indicate that most companies assume a capitalization rate of between 8.5 and 11% - in other words, internal industry estimates of what it costs to develop a drug over time now run higher, on average, than the actual returns from developing one. Another alarming bit of news is their analysis of Phase III failures. From 1990 to 2007... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2688906 Mon, 10 Aug 2009 11:28:07 +0100 2688906 http://www.medworm.com/index.php?rid=2513139&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F06%2F22%2Ffunky_carbocycles.php Earlier this month I posted about rolofylline, which I noted has a rather unusual noradamantane attached to it. Now check out this ORL-1 compound from Banyu, complete with the not-so-widely-heard-of bicycloheptane-spirocyclopropane group. This was not arrived at lightly, as you'd imagine. There's a table in the Supporting information for the paper, but I'll quote from the body of the main manuscript: Various kinds of cycloalkanes, substituted or nonsubstituted cyclopropyl rings to medium sized rings (such as cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl, cyclononylmethyl, cyclodecylmethyl), spiroalkane (such as spiro[2.5]octanemethyl, spiro[3.5]nonanemethyl, spiro[4.5]decanemethyl, spiro[2.4]heptanemethyl, spiro[3.4]octanemethyl, spiro[4.4]nonanemethyl), bicycl... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2513139 Mon, 22 Jun 2009 12:53:06 +0100 2513139 http://www.medworm.com/index.php?rid=2513142&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F06%2F19%2Fmore_hot_air_from_me_on_screening.php After yesterday's post on pathway patents, I figured that I should talk about high-throughput screening in academia. I realize that there are some serious endeavors going on, some of them staffed by ex-industry people. So I don't mean to come across as thinking that academic screening is useless, because it certainly isn't. What is probably is useless for is enabling a hugely broad patent application like the one Ariad licensed. But the problem with screening for such cases isn't that the effort would come from academic researchers, because industry couldn't do it, either: Merck, Pfizer, GSK and Novartis working together probably couldn't have sufficiently enabled that Ariad patent; it's a monster. It's true that the compound collections available to all but the very largest academic eff... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2513142 Fri, 19 Jun 2009 12:43:33 +0100 2513142 http://www.medworm.com/index.php?rid=2513145&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F06%2F17%2Fthe_view_from_pfizers_corner_offices.php There's a good article from Lee Howard up at The Day (the New London/Groton newspaper) on the changes going on at Pfizer. It's the story according to management, though, which is worth having for its compare-and-contrast uses: Despite the looming uncertainty, according to company spokesmen, the new research structure has added energy and urgency to the drug-discovery process in Groton. . . . . .The changes in Groton - seen most plainly in displays of logos the new business units are in the process of choosing - have added drug-development staff and even legal experts to the R&D mix, along with biologists and chemists who typically have worked in close proximity. In the middle of it all sits the chief scientific officer of each business unit, as well as other managers. The idea is to dev... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2513145 Wed, 17 Jun 2009 13:18:07 +0100 2513145 http://www.medworm.com/index.php?rid=2513147&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F06%2F15%2Fugliness_defined.php Yesterday's post on so-called "ugly" molecules seems to have touched a few nerves. Perhaps I should explain my terms, since ugliness is surely in the eye of the beholder. I'm not talking about particular functional groups as much as I'm talking about the whole package. First off, a molecule that does what it's supposed to do in vivo is (by my definition) not truly ugly. The whole point of our job as medicinal chemists is to make active compounds - preferably with only the activity that we want - and if that's been accomplished there can be no arguing. Of course, "accomplished" has different meanings at different stages of development. Very roughly, the mileposts (for those of us in discovery research) are: 1. Hitting the target in vitro. 2. Showing selectivity in vitro. 3. Showing blood ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2513147 Tue, 16 Jun 2009 01:31:39 +0100 2513147 http://www.medworm.com/index.php?rid=2442745&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F05%2F21%2Fthe_nih_takes_the_plunge.php The NIH has announced that they're going to start up a preclinical drug discovery effort to address rare diseases. I find this interesting for several reasons. For one thing, it's worth a try for conditions where no company has seen a way to fund research, and there are quite a few of them. Treating rare diseases can be quite profitable in the industrialized world (ask Genzyme, among other companies), but if the conditions are localized in poorer areas no one's likely to take a crack at them. So my first reaction is "Good, and the best of luck to you". The NIH has been getting closer to doing preclinical drug discovery in recent years, so this is a logical next step. The second thought I have is that this will be an interesting experience for the researchers involved. There's nothing quit... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2442745 Thu, 21 May 2009 11:41:31 +0100 2442745 http://www.medworm.com/index.php?rid=2341840&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F04%2F13%2Fan_hiv_drug_or_a_gout_drug_or_both_.php We get a lot of surprises in this business, most of them not so good. That's understandable, since there are lot more ways for drugs and their mechanisms to go wrong than there are for them to go right. But once in a while, you do see something that's unexpectedly good news. That may be what's happened to a small San Diego outfit, Ardea. As Xconomy details, the company (formed out of the remnants of IntraBiotics and Valeant) was testing an HIV compound in the clinic when they noticed significant declines in blood levels of uric acid. That rang a bell: something that decreases uric acid levels would be useful for gout, and there's only been one new gout drug approved in the last 40 years. Follow-up work showed that the effect seemed to be coming from a metabolite of the original drug, and... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2341840 Mon, 13 Apr 2009 12:48:46 +0100 2341840 http://www.medworm.com/index.php?rid=2300961&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F04%2F03%2Fthe_mechanical_chemist.php We use a lot of automated equipment in the drug discovery business. There’s an awful lot of grunt work involved, and in many cases a robot arm is better suited to the task – transferring solutions, especially repetitive transfers of large numbers of samples, is the classic example. High-throughput screening would just not be possible if you had to do it all by hand; my fingers hurt just imagining all the pipetting that would involve. But I wouldn’t say that the process of medicinal chemistry is at all automated. That’s very much human-driven, and a lot of the compounds on most med-chem projects are made by hand, one at a time. Sure, there are parallel synthesis techniques, plates and resins and multichannel liquid handlers that will let you set up a whole array of reactions at onc... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2300961 Fri, 03 Apr 2009 13:45:34 +0100 2300961 http://www.medworm.com/index.php?rid=2323819&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2FcKphE4nAsD4%2F Interesting post from Joerg, who is not so sure about open innovation in drug design. He makes some good points, with the observation In other words, if you do not need the money, do whatever you like openly. If you need the money, e.g. for clinical trials, then please make sure staying within the same legal framework, which is most probably not open! And here is where I diverge. The very essence of the Creative Commons movement, the setting up of open source licenses, etc was to provide an open, legal framework for sharing content or software. Such a framework doesn’t exist in the drug discovery world, so yes, today open innovation is difficult. But that doesn’t mean it is not a goal we should not seek to attain. We need the Larry Lessig types who will push the open innovat... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=2323819 Mon, 30 Mar 2009 23:09:46 +0100 2323819 http://www.medworm.com/index.php?rid=2323821&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2FcQTsGDa6N6s%2F Image via Wikipedia So I am supposed to be writing about innovation in the Biopharma industry. Here’s in idea that I’ve had that might be worth discussing (sometimes I wish I had the patience to write with the depth of Michael Nielsen). Last year we heard about Goldman Sachs funding an innovative pharma business model, but at that time I felt that the stage they had chosen was too late. One of the biggest expenses in pharmaceutical drug development is attrition. For all kinds of reasons, various programs never make it, leads are discarded, etc. I wonder if there is a place for marketplace or pool where companies can throw in discarded compounds or programs. Then, someone else can pick up a compound, or lead series or two, associated information which could be made available (ne... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=2323821 Mon, 30 Mar 2009 06:51:28 +0100 2323821 http://www.medworm.com/index.php?rid=2260172&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2F-ADU6v2C370%2F Image via Wikipedia Chris asked me to talk about biotech and innovation, so I don’t really have a choice. This is just a preamble, and more will come down the road. Over the years, I have talked a lot about innovation, especially in the life sciences. Earlier today, I started a bit of a discussion on Friendfeed and Twitter when I responded to a tweet by Tim O’Reilly. In a talk at E-Tech, Drew Endy apparently said that big money requirements of biotech are holding it back and one could make biotech innovation more like software and innovate much faster. Admittedly this is absent of context, but I responded to that tweet with one that said that while there is definitely a lot to learn, instruments and people cost money. My focus was actually on the latter. In the world of softwar... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=2260172 Wed, 11 Mar 2009 05:56:44 +0100 2260172 http://www.medworm.com/index.php?rid=2260915&cid=t_105099_150_f&fid=34889&url=http%3A%2F%2Fpharmamkting.blogspot.com%2F2009%2F03%2Fas-innovation-shifts-to-small-companies.html (Source: Pharma Marketing Blog) Pharma Marketing Blog blogs http://www.medworm.com/rss/comments.php?id=2260915 Mon, 09 Mar 2009 11:32:00 +0100 2260915 http://www.medworm.com/index.php?rid=2153088&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2009%2F02%2F02%2Fopen_pharma.php Several readers pointed out the comments of Paul Stoffels, head of R&D at Johnson & Johnson, as reported in the Wall Street Journal’s Health Blog. He’s boosting some sort of open-pharma research model, although what he means by that isn’t too clear: “All simple diseases have been solved,” Stoffels said. “The next-generation drugs, therapies, are much more complex… You need much more information and science than what you can get out of your own internal labs.” . . . The future of the drug industry, Stoffels told the Health Blog, is “building networks where together with a number of different groups you come up with solutions to solve different medical needs.” There are a couple of things worth noting in there. The comment about all simple diseases having been solved, f... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2153088 Mon, 02 Feb 2009 13:14:23 +0100 2153088 http://www.medworm.com/index.php?rid=2027172&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2F0AtMxikt4PA%2F And while we are on the subject of blog posts by Derek Lowe, here’s one where he points to news about Goldman Sachs funding a large pharma company and using a “new” business model (The model involves) a different approach, creating a “research pool” into which pharma companies would place a range of experimental drugs in a single therapeutic area in early-stage phase 1 and 2 trials, where their specialists would work alongside external experts including scientists, chemists and clinical research organizations. That’s a model that I am sure I’ve heard being mentioned somewhere else, although I can’t remember. The concept is one that does appeal to me in general, but is phase 1 or 2 the correct time? A lot of the attrition occurs in pre-clinica... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=2027172 Thu, 11 Dec 2008 06:01:38 +0100 2027172 http://www.medworm.com/index.php?rid=2027173&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2FQyY8g5lof5k%2F Image via WikipediaGreat post by Derek Lowe as usual, and about an area of science that I care about deeply. In general, molecular recognition, and specifically, the energetics of drug binding are among the most fascinating subjects I have every come across. Fascinating not just because of the science, but also for now important they are and how difficult a problem it is to solve properly computationally. Our current methods to calculate free energy landscapes and the true energetics of drug binding are crude at best (at least the ones that are realistic). Our representation of the entropy term is especially poorly represented and is a part of recognition we barely optimize for. As Derek suggests, the medicinal chemists to drug discovery is to optimize for the enthalpic term, using rings t... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=2027173 Thu, 11 Dec 2008 05:47:14 +0100 2027173 http://www.medworm.com/index.php?rid=2006391&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F12%2F01%2Fprodrugs_how_the_pros_do_it.php I’m going to write this morning about a question that actually came up among several of us at the train station this morning. I’m on a route that takes a lot of people into Cambridge, so we have a good proportion of pharma/biotech people on board. And today we got to talking about prodrugs: like 'em or hate 'em? For those not in the business, a prodrug is a masked form of an active drug, designed to be activated once it’s dosed. That’s generally done by allowing the normal metabolic processes of the body to clip some group off, revealing the real drug. Various esters are the most common prodrugs, since that’s about the easiest group to have fall apart on you. (Enalapril / enalaprilat is a classic example, and aspirin is an even more classic one). And esters illustrate another p... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=2006391 Mon, 01 Dec 2008 13:22:19 +0100 2006391 http://www.medworm.com/index.php?rid=1975629&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F11%2F20%2Fnoisy_numbers.php A colleague e-mailed me last night with an observation that he’d heard recently: “Have you noticed,” he said, “that the number we use get less and less precise, the farther away they get from the chemists?” Thinking about it, I’d have to say that’s right, although I don’t think that we can claim any particular credit. After all, we have our feet planted in physics. Our molecular weights are based on the weights of the elementary particles, which are known. . .pretty exactly. And we’ve got a pretty good handle on molecular formulae, too, so we can go around getting mass spectra out to four decimal places and learning all kinds of things from them. But then when these compounds get run through the primary assays, purified enzymes or the like, the numbers start getting fuz... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1975629 Thu, 20 Nov 2008 13:42:08 +0100 1975629 http://www.medworm.com/index.php?rid=1960827&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeedproxy.google.com%2F%7Er%2Fmndoci%2F%7E3%2Ft-m_eJ4liSY%2F Looks like Allen Roses has a boutique consultancy focussed on pharmacogenetics. For those who don’t know Allen Roses, he is a former head of genetics research at GlaxoSmithKline and Director of Duke University’s Deane Drug Discovery Institute. The latter came to my attention when I saw an article on PGx Reporter (might require a sub) about the Drug Discovery Institute which called the institute a new model designed to fill the void between academic drug discovery and translational medicine. The whole idea of a virtual pharma has been floated around by different people under different guises and something I’ve alluded to often over time, but I definitely liked the mindset behind Roses’ thinking. The idea is to build a think tank with knowledge of every step of the drug d... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1960827 Wed, 12 Nov 2008 02:17:48 +0100 1960827 http://www.medworm.com/index.php?rid=1895592&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmalot%2F%7E3%2F427742712%2F Last week, Kevin Huang, the editor of the Harvard Health Policy Review, a student-run journal with a tiny circulation, received an e-mail from Richard Frank, a Harvard Medical School health economics professor, to say that a recently published article about medical journals and ethical standards was unfair to Frank and two of his colleagues. As a result, he would no longer serve as an advisor to the publication. In response, Huang pulled the site down for further review. Why the fuss? The objectionable article was written by Donald Light and Rebecca Warburton, who chronicled an episode that took place four years ago concerning an earlier article they wrote for the Journal of Health Economics. In that piece, they chastised a widely cited study published in 2003 in the same journal that clai... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=1895592 Tue, 21 Oct 2008 18:42:49 +0100 1895592 http://www.medworm.com/index.php?rid=1886679&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F10%2F17%2Fdown_the_chute_in_phase_iii.php Here's a good article over at the In Vivo Blog on this year's crop of expensive Phase III failures. They've mostly been biotech drugs (vaccines and the like), but it's a problem everywhere. As In Vivo's Chris Morrison puts it: Look, drugs fail. That happens because drug development is very difficult. Even Phase III drugs fail, probably more than they used to, thanks to stiffer endpoints and attempts to tackle trickier diseases. Lilly Research Laboratory president Steve Paul lamented at our recent PSA meeting that Phase III is "still pretty lousy," in terms of attrition rates -- around 50%. And not always for the reasons you'd expect. "You shouldn't be losing Phase III molecules for lack of efficacy," he said, but it's happening throughout the industry. Ah, but efficacy has come up in the... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1886679 Fri, 17 Oct 2008 12:49:31 +0100 1886679 http://www.medworm.com/index.php?rid=1879805&cid=t_105099_122_f&fid=34755&url=http%3A%2F%2Fneuropsychological.blogspot.com%2F2008%2F10%2Fneuropsychology-abstract-of-day_15.html Becker RE & Greig NH. Alzheimer's disease drug development in 2008 and beyond: Problems and opportunities. Current Alzheimer Research. 2008 Aug; 5(4): 346-357.Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the fa... BrainBlog blogs http://www.medworm.com/rss/comments.php?id=1879805 Wed, 15 Oct 2008 23:30:00 +0100 1879805 http://www.medworm.com/index.php?rid=1848099&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F10%2F02%2Ftaranabant_is_no_more.php Merck has taken a step that many people have been expecting, and announced that they are no longer developing taranabant, their cannabinoid antagonist (or is it an inverse agonist?) I'd expressed grave doubts about the drug earlier this year, which turned out to be well-founded. That latter post included the line "I don't see how they can get this compound through the FDA", and now Merck seems to have come to the same conclusion. Further clinical data seem to have shown far too many psychiatric side effects (anxiety, depression, and so on), which increased along with the dose of the drug. The cannabinoid antagonist field has already experienced a crisis of confidence after Sanofi-Aventis's rimonabant failed to gain approval in the US. This latest news should ensure that no company tries ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1848099 Thu, 02 Oct 2008 15:54:34 +0100 1848099 http://www.medworm.com/index.php?rid=1769133&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F09%2F05%2Fsamurai_unleash_your_drug_candidates.php Today’s ration of scientific confusion comes courtesy of Wired, in an article that talks about using a modified form of TMV (tobacco mosaic virus) for delivering silencing RNAs. A group at Maryland has used the virus to deliver various siRNAs to cell lines in vitro, which is an interesting idea. But then it gets the Wired treatment: The short, double-stranded RNA molecules known as siRNA can program cells to destroy disease-causing proteins. Their molecules turn on a cell's own built-in disease-fighting mechanisms. They can be programmed for a wide range of ailments -- from cancers to viruses -- and because they use the cell's own defense mechanisms, they produce minimal side effects. In addition to treating cancers and genetic disorders, siRNA could prove useful against a variety of ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1769133 Fri, 05 Sep 2008 12:27:30 +0100 1769133 http://www.medworm.com/index.php?rid=1742935&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F08%2F29%2Fsticky_containers_vanishing_drugs.php There’s no end to the variables that can kick your data around in drug discovery. If you concentrate completely on all the things that could go wrong, though, you’ll be too terrified to run any useful experiments. You have to push on, but stay alert. It’s like medical practice: most of the time you don’t have to worry about most of the possibilities, but you need to recognize the odd ones when they show up. One particular effect gets rediscovered from time to time, and I’ve just recently had to take it into account myself: the material that your vials and wells are made out of. That’s generally not a consideration for organic chemists, since we work mostly in glass, and on comparatively large scale. There are some cases where glass (specifically the free OH groups on its surfa... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1742935 Fri, 29 Aug 2008 12:52:05 +0100 1742935 http://www.medworm.com/index.php?rid=1720548&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F08%2F20%2Freplacing_whats_being_lost.php Well, today’s subject isn’t a cheerful data set, but it certainly deserves some thought. Over at Pharmalot, Ed Silverman has some data from consulting firm AVOS Life Sciences, who have sat down to estimate how well various drug companies will do with revenue from new drugs over the next few years. As of 2007, they have the industry average at about 77 cents coming from new products (defined as those launched within the previous five years) for every dollar lost from patent-expiring older ones. That doesn’t sound very good, but the average is a bit misleading, since it runs from the highs of Eli Lilly ($6.64/1), Amgen ($4.50/1) and Roche ($4.03/1) down to Sanofi-Aventis (11 cents new per dollar loss on the old). But it’s true that most everyone else is well under a dollar. It would... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1720548 Wed, 20 Aug 2008 12:29:47 +0100 1720548 http://www.medworm.com/index.php?rid=1714174&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2541 At the American Chemical Society national conference last weekend, Rensselaer Polytechnic researcher Dr. Robert Linhart announced that his team may have built the first fully synthetic heparin. Whether or not you believe that the possibility of another contamination crisis of natural raw heparin exists, the potential for a heparin supply independent of the whims and [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1714174 Mon, 18 Aug 2008 16:56:49 +0100 1714174 http://www.medworm.com/index.php?rid=1692387&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2521 Yesterday’s announcement that Eli Lilly had sold off its Greenfield, Indiana, R&D facility to Covance is perhaps not just a big deal, but really a bellwether move that may signal a trend of Big Pharma companies not just outsourcing aspects of their R&D operations but selling them off altogether. As the above-linked article suggests, the [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1692387 Fri, 08 Aug 2008 15:10:21 +0100 1692387 http://www.medworm.com/index.php?rid=1679630&cid=t_105099_150_f&fid=35781&url=http%3A%2F%2Fwww.qdinformation.com%2Fqdisblog%2F2008%2F08%2F04%2Fmore-news-on-biogenerics-medical-news%2F After being away for sometime for a variety of reasons including a pinched nerve in my neck, I’m finally back and hoping to post to this blog several times a week, although I doubt I will be able to get back to posting daily due to work and other issues. I did find the following article I found recently interesting as it talks about differences in Congress regarding biogenerics. AMNews: Aug. 11, 2008. Disagreements slow progress on biogenerics legislation … American Medical News: I think the point about the period of exclusivity is a valid point and where I think the the greatest debate will occur. While it may take a while to get compromise I think something will indeed happen on this front in the next year. It may not be a great bill but at least it will be something Google: ... QDIS Blog blogs http://www.medworm.com/rss/comments.php?id=1679630 Mon, 04 Aug 2008 20:56:31 +0100 1679630 http://www.medworm.com/index.php?rid=1679628&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2481 A paper by James Evans recently published in Science, explores the impact of the Internet on research publications.  The problem:  Fewer and more recent sources are being cited.  For a video interview with Evans, click here. Emil Ciurczak expounded on this theme a while back, describing this as the “Cool Hand Luke” effect….what we have, [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1679628 Mon, 04 Aug 2008 17:39:48 +0100 1679628 http://www.medworm.com/index.php?rid=1671576&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F352255123%2F Image via WikipediaMy graduate advisor’s favorite word, or at least one of the more popular ones, was serendipity. He was a firm believer in the role of serendipity in science, and personally I believe that serendipity plays a big role in discovery, of any kind. So when Richard Jones pointed to a story in the Financial Times entitled Drug Research Needs Serendipity, it naturally piqued my interest. The article has an ominous start The molecular revolution was supposed to enable drug discovery to evolve from chance observation into rational design, yet dwindling pipelines threaten the survival of the pharmaceutical industry. What went wrong? Lest you think that this is some journalist writing a story, look at who wrote the piece. David Shaywitz (a well known writer covering health and... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1671576 Fri, 01 Aug 2008 04:36:37 +0100 1671576 http://www.medworm.com/index.php?rid=1652553&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F07%2F24%2Fconfident.php I’m going to expand on one of the points brought up yesterday, about the reported drug industry executive who was confident that his company’s Alzheimer’s therapy was ready to go out and make billions of dollars. It was that word “confident” that set me off, I think. Because that’s not a word that you hear much of in this industry. The strongest form that you’ll come across is something like “fairly confident”, which is how you feel when you send in a compound that’s a minor change off something that’s already active, or how you feel about screening a target that’s a close homologue of something you already have plenty of ligands for. You can be pretty sure in those cases that something’s going to hit – but you’ll note that both of those are pretty far upstre... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1652553 Thu, 24 Jul 2008 12:16:22 +0100 1652553 http://www.medworm.com/index.php?rid=1631586&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2301 We received an office visit today from Dr. Prabir Basu, executive director of the National Institute for Pharmaceutical Technology and Education, or NIPTE. (He’s also head of Purdue University’s Pharmaceutical Technology Education Center.) NIPTE, in case you haven’t heard, is a not-for-profit consortium of 11 universities whose mission is to further scientific education and training [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1631586 Wed, 16 Jul 2008 21:11:14 +0100 1631586 http://www.medworm.com/index.php?rid=1616163&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F333691589%2F Image by Eran Kampf via FlickrEnlight Biosciences might just be the sign of new times. Over the past few years, several pharma companies have come together on a number of efforts, e.g. the Critical Path Institute. I’ve heard enough people in senior positions in pharma talk about the need to share pre-competitive information over the past couple of years to believe that an apparent move to co-develop, or at least invest in technologies that are unlikely to give a company a competitive advantage, has some legs. The scientific weight behind Enlight makes an impressive list, as does the list of pharma partners, and the areas of interest (a little too broad and general if you ask me). It looks like their current focus is on in vivo imaging. The part that troubles me a little. It’s a... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1616163 Sat, 12 Jul 2008 18:24:10 +0100 1616163 http://www.medworm.com/index.php?rid=1603410&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2271 LabJabPharma.com, a new forum, aims to do for R&D what Cafe Pharma does for sales.  There are other more formal forums, like the AAAS career forum that are currently very active, but this one is focused on pharma and appears to be modelled after Cafe Pharma. Since it’s so new, it’s a “clean slate” right now. [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1603410 Wed, 09 Jul 2008 19:55:48 +0100 1603410 http://www.medworm.com/index.php?rid=1594012&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2251 “Not Invented Here” syndrome is a factor in many businesses today. It usually means reluctance to use technology that was developed elsewhere.  However, according to some sources, the drug industry has turned the phrase on its head, depending almost exclusively on innovations that were developed elsewhere (including NIH) In a letter to the Wall Street Journal recently, Harvard [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1594012 Tue, 08 Jul 2008 02:48:50 +0100 1594012 http://www.medworm.com/index.php?rid=1594009&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmalot%2F%7E3%2F328813476%2F The drugmaker is taking the unusual step of giving government healthcare systems a say in deciding which drugs advance in its research pipeline, a move it hopes will result in more products these customers will pay for, The Wall Street Journal writes. Glaxo’s new ceo, Andrew Witty, tells the paper the effort is part of his drive to adapt as rising prices have prompted insurers, governments and other payers to tighten their belts. “I’m going to deal with the pharmaceutical realities of the next 10 years, and they’re very different from those of the 1990s,” Witty says in an interview at a company townhouse in London. Knowing the preferences of state health-care systems, which pay for most drugs sold in Europe, could make a big difference, the paper writes. A few... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=1594009 Mon, 07 Jul 2008 11:46:45 +0100 1594009 http://www.medworm.com/index.php?rid=1563962&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F325486994%2F Image via WikipediaIt is unlikely that I will be able to attend the Health 2.0 conference this year, but there are definitely some rather interesting talks this year, as highlighted on the Health 2.0 blog. Looking at the lineup though reminded me of a discussion I had with a big pharma CIO a few years ago. He had just given a talk about clinical data integration and I was picking his brains on genomic data. He told me that he wanted to bring genomic data into the company’s clinical data pipelines but didn’t really have a good idea of how they were going to do it. We talk a lot about Health 2.0 in the social health or crowd sourced context, but what about the future of medicine, the therapies that will guide our future? For the better part, some of the real challenges of all the... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1563962 Thu, 03 Jul 2008 05:04:58 +0100 1563962 http://www.medworm.com/index.php?rid=1546988&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fa4.g.akamai.net%2F7%2F4%2F33930%2Fv1%2Fsmb2.download.akamai.com%2F33930%2FPM%2FDW_D0013.mp3 A storm, complete with hail, thunder and generous amounts of lightning, appeared to follow me through Connecticut and Rhode Island as I drove to Boston on Wednesday for the DIA meeting.  Didn’t make it until almost 4 PM, only to have the storm break out in Boston at 6 PM in all its glory.  Although I’d missed the [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1546988 Thu, 26 Jun 2008 19:30:28 +0100 1546988 http://www.medworm.com/index.php?rid=1535805&cid=t_105099_97_f&fid=35050&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmaGazette%2F%7E3%2F316271911%2Fvirtual_man_may_reduce_drug_testing_time.html Reuters is reporting on developing technology that may help pharmaceutical manufacturers reduce the research cost and time currently required for the testing of new drugs.New computing technologies which have developed "Virtual Man" (virtual physiological human or VPH) may be able to predict the effects of new drugs in pharmaceuticals' pipelines prior to clinical trials. It has been estimated that drug research time may be shortened by two thirds, the cost of clinical trials significantly decreased and productivity increased. (Source: PharmaGazette) PharmaGazette blogs http://www.medworm.com/rss/comments.php?id=1535805 Fri, 20 Jun 2008 18:00:35 +0100 1535805 http://www.medworm.com/index.php?rid=1531696&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2181 One session on Wednesday morning addressed the use of molecular modeling in drug development. Ian Wilson, Portfolio and Strategy Manager, GE Healthcare discussed the development of PET clinical biomarkers. He mentioned the need to collaborate early, and the fact that academic partners can be great partners.  One important question to ask, he notes, is whether [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1531696 Fri, 20 Jun 2008 17:31:32 +0100 1531696 http://www.medworm.com/index.php?rid=1531698&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2161 Missed Madame Piramal’s presentation, unfortunately, while running back and forth between segments of the building and the show floor. The message behind speakers at the session on Indian Biotech was clear: don’t think “low cost,” think innovation. BMS alumnus Rashmi Barbhaiya used the Nano, India’s new model car, as a metaphor. He and Ramesh Adige, director [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1531698 Fri, 20 Jun 2008 16:27:42 +0100 1531698 http://www.medworm.com/index.php?rid=1531703&cid=t_105099_150_f&fid=35779&url=http%3A%2F%2Fwww.pharmamanufacturing.com%2Fonpharma%2F%3Fp%3D2111 On Tuesday afternoon, a panel discussed ways in which corporations might be able to stimulate the development of more therapies for serious diseases—-the world’s top killers such as malaria. The topic is one that I’m very interested, but, unfortunately, I arrived late and missed much of the discussion. Genzyme has been doing some pioneering work with [...] (Source: On Pharma) On Pharma blogs http://www.medworm.com/rss/comments.php?id=1531703 Fri, 20 Jun 2008 14:49:31 +0100 1531703 http://www.medworm.com/index.php?rid=1423277&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F284391217%2F Here is the abstract of a paper in Hypertension entitled Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Angiotensin-converting enzyme 2 (ACE2) is a key renin-angiotensin system enzyme involved in balancing the adverse effects of angiotensin II on the cardiovascular system, and its overexpression by gene transfer is beneficial in cardiovascular disease. Therefore, our objectives were 2-fold: to identify compounds that enhance ACE2 activity using a novel conformation-based rational drug discovery strategy and to evaluate whether such compounds reverse hypertension-induced pathophysiologies. We used a unique virtual screening approach. In vitro assays revealed 2 compounds (a xanthenone and resorcinolnaphthalein) t... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1423277 Tue, 06 May 2008 05:40:13 +0100 1423277 http://www.medworm.com/index.php?rid=1416436&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F05%2F02%2Fnot_useful_means_not_approvable_right.php One recent drug industry setback I haven't noted around here - well, OK, to be more specific, it's a Merck setback, and boy must they be getting sick of those - is the FDA's "not approvable" letter for the Singulair/Claritin combination pill. As the folks at the InVivoBlog note, it sure was hard, from one perspective, to see that one coming. After all, Claritin (loratadine) has an exemplary safety record and has been on the market for many years now, and Singulair (montelukast) has been selling in the billions of dollars as a stand-alone drug. No doubt many people have taken, and are taking, the two as separate pills. So you combine them and get a "not approvable": right. The In Vivo people speculated that this might be a safety problem, since the agency has been mighty jumpy about that ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1416436 Fri, 02 May 2008 12:52:13 +0100 1416436 http://www.medworm.com/index.php?rid=1409769&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F280709573%2F A quick report on Day 2 of Bio-IT World. The day started with a keynote by Josh Boger, founder and CEO of Vertex. His talk spanned several real world examples and some food for thought. Highlights Vertex has made active use of a MedChem ELN, which has been extended to their entire MedChem community, including external partners. In his own words the goal was “enabling the virtual research organization” Metric of success was user adoption and there were some good analytics supporting uptake He spoke at length about the HCV program, where they have used extensive predictive modeling and simulation Clinical data has backed up their predictive modeling (they’re in Phase III now) They have avoided some experiments (carried out by competitors in one case) that their models sug... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1409769 Wed, 30 Apr 2008 10:43:39 +0100 1409769 http://www.medworm.com/index.php?rid=1379587&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmalot%2F%7E3%2F272122014%2F The agency is considering using seven biomarkers that signal kidney injury when found in the uring of test subjects in hopes of moving drugs to market faster and reducing patient risk, The San Francisco Chronicle writes. And an announcement is expected any day, according to one FDA official. “Today, the FDA gives approval for a new drug or device, but there has previously been no way to obtain approval for a new and better way to test a drug for its safety,” Ray Woosley, ceo the nonprofit Critical Path Institute, which is working with the FDA to safely speed drug development, tells the paper. Currently, experimental drugs are tested in animals before being taken to human clinical trails. But animal reactions aren’t always the best predictor of whether substances will be s... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=1379587 Thu, 17 Apr 2008 11:56:38 +0100 1379587 http://www.medworm.com/index.php?rid=1354201&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F04%2F07%2Fpreemption_for_real.php There's talk again about an idea that's been kicking around for some years: are drug companies shielded from liability after the FDA has approved their drugs for sale? Obviously, the current answer is "Not at all": consider the lawsuits over Vioxx. But the decision by the Supreme Court in February in Riegel v. Medtronic has the idea being taken seriously again. That ruling seems to shield medical device companies from lawsuits over safety or efficacy after the FDA has signed off on those issues - as long as the device is the same, and used in the approved manner. And no, for the politically motivated among the readership, this wasn't some barely-realized 5:4 scheme from Justice Scalia; the decision went 8 to 1. There's a roughly similar case before the court now, Wyeth v. Levine. At issu... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1354201 Mon, 07 Apr 2008 12:30:39 +0100 1354201 http://www.medworm.com/index.php?rid=1344326&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F262154974%2F Algorithms or data? I can see the arguments starting right now. Just kidding of course, but a company called Provisio has a service called iTrials that captures information from 60 million patients to help make decisions about patient enrollment. The key goal is to try and figure out how many patients can be enrolled in a trial, and being able to make good decisions there can save a lot of money. Two thoughts came to mind First of all how much data is good data. 60 million sounds like a lot, but in the grand scheme of things, with trials going global it may not really be that much When patient enrichment and other trial approaches, driven by genetics, become more common, how is this information going to be used? I am early in my days of understanding trial selection, etc, so there are al... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1344326 Tue, 01 Apr 2008 14:37:19 +0100 1344326 http://www.medworm.com/index.php?rid=1325471&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F03%2F25%2Fgetting_to_lyrica.php There’s an interesting article in Angewandte Chemie by Richard Silverman of Northwestern, on the discovery of Lyrica (pregabalin). It’s a rare example of a compound that came right out of academia to become a drug, but the rest of its story is both unusual and (in an odd way) typical. The drug is a very close analog of the neurotransmitter GABA. Silverman’s lab made a series of compounds in the 1980s to try to inhibit the aminotransferase enzyme (GABA-AT) that breaks GABA down in the brain, as a means of increasing its levels to prevent epileptic seizures. They gradually realized, though, that their compounds were also hitting another enzyme, glutamic acid decarboxylase (GAD), which actually synthesizes GABA. Shutting down the neurotransmitter’s breakdown was a good idea, but shut... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1325471 Tue, 25 Mar 2008 12:19:17 +0100 1325471 http://www.medworm.com/index.php?rid=1322421&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F03%2F24%2Fthats_never_gonna_work.php A colleague and I were talking the other day about the (long) list of drugs that have been left for dead at some point during their development. There are some famous cases – Lipitor, for example, which wasn’t thought by many at Warner-Lambert to have a business case worth even taking into the clinic. But these things are all over the place. One that I know about was Claritin (loratadine). Schering-Plough worked on nonsedating antihistamines for a while, without too much success, and the whole program was eventually killed. The head of research at the time stated flatly: “There are no nonsedating antihistamines”. Of course, when the first one (Seldane) came on the market, that made everyone rethink a bit. In the interim, one of the chemists had continued making compounds, despite ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1322421 Mon, 24 Mar 2008 13:14:21 +0100 1322421 http://www.medworm.com/index.php?rid=1294726&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmalot%2F%7E3%2F249582026%2F With all the handwringing over dry pipelines, clinical trial failures and few regulatory approvals, a pair of Bear Stearns venture capitalists published an interesting analysis in the latest issue of Nature Reviews Drug Discovery and found that pharma and biotechs* may just improve their odds if they worked together more often. They analyzed the origins of drugs approved by the FDA and those failing in Phase III trials between January 2006 to December 2007. Here’s what they found: Of the 103 FDA approvals, 47, or 45 percent, were from biotech; 16, or 16 percent, were from pharma-biotech alliances; and 40, or 39 percent, were from drugmakers (four of which were acquired or licensed from biotechs). In short - 67 NDAs, or 65 percent, originated from biotechs. They also segmented drugs b... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=1294726 Tue, 11 Mar 2008 16:10:21 +0100 1294726 http://www.medworm.com/index.php?rid=1286442&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F03%2F07%2Fdissolve_your_troubles_away.php Hang around any drug discovery organization and you’ll hear complaints about how the drug candidates don’t dissolve well. The people who test the compounds on cells and proteins complain a bit about this, and the ones who test on mice and rats complain even more. Traditionally, the problem eventually lands on the lab benches of the people who work out formulations, who complain that by the time it gets to them that there’s only so much than can be done. So over the years, it’s become more of a concern for the chemists who make the things in the first place, as I guess it should. Solubility isn’t the single most important factor in making drug candidates, but you can’t ignore it, either. Having a drug that dissolves well frees you up during development. Whenever you get low or ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1286442 Fri, 07 Mar 2008 14:09:46 +0100 1286442 http://www.medworm.com/index.php?rid=1252652&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F240230630%2F At the scienceblogging conference, someone raised the point that the structural biology community has been depositing raw data into the public domain for a long time and pretty much all protein structures (other than the co-crystal structures generated by pharma companies) are pretty much open access. So it shouldn’t come as a surprise when the head of the structural genomics effort comes out in support of open data (free registration reqd). Amongst other things Al Edwards equated finding new drugs to the “lottery” and argues that open data is essential to improve our chances of developing better drugs. While the biopharma industry is using more and more sophisticated techniques, both to fail early (rather than expensively in the clinical trial phase) and to find better d... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1252652 Sun, 24 Feb 2008 05:41:35 +0100 1252652 http://www.medworm.com/index.php?rid=1240218&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F237184290%2F The TED blog points us to the release of Grand Challenges for Engineering released by the National Academy of Engineering. In other words, not something to be taken lightly. Over the next few days, I am going to discuss some of these challenges We start with the challenge to Engineer better medicines. The story is not new. We all know (or are in denial) that the traditional approach to drug development, aka the blockbuster model, is not cutting it any more. What we need are new approaches to drug development and new ways to approach and understand diseases, disease prevention and disease treatment. Where do the grand challenges lie? Well, there is a laundry list of challenges, but many are focused on the same problem; how can we leverage our increasing knowledge of human genetics and syste... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1240218 Mon, 18 Feb 2008 21:22:36 +0100 1240218 http://www.medworm.com/index.php?rid=1207478&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F230137941%2F That’s about as cliched a title as it gets, but it’s also one of the premier challenges facing scientists, especially those in pharma, at many levels. The challenge only gets amplified when one thinks beyond basic drug discovery and moves further downstream, or even beyond NDA. For my second post for Just Science Week, I thought that looking at a paper from Loging et al on High Throughput Electronic Biology in the context of some of the other threads seen previously on bbgm might be an interesting exercise. First and foremost, the paper is one that looks at the available high throughput methods to mine data and make sense out of it. As the authors note, drug discovery is hard and complex. While we’ve all waited for the post-genomic era to really bear fruit and deliver new... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1207478 Wed, 06 Feb 2008 07:54:43 +0100 1207478 http://www.medworm.com/index.php?rid=1161227&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2008%2F01%2F18%2Feat_it_breath_it_soak_in_it.php After Pfizer’s Exubera inhaled-insulin product died so horribly in the market last year, the other companies working in the same space had to be worried. Lilly and Alkermes have had a long-running program, as has a smaller company called Mannkind. But recently, another contender, Novo Nordisk, has announced that they and partner Aradigm have decided to cut their losses. The In Vivo Blog has an excellent roundup. According to Novo’s CEO, they (like Pfizer) were focusing on prandial insulin because that was basically the only thing they could get to work through inhalation. Now that they’ve seen how well that went over, they’ve decided to spend the money on different proteins (basal insulin, glucagon-like-peptide 1 analogs, etc.) They have a GLP-1 analog in Phase III, but apparently... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1161227 Fri, 18 Jan 2008 13:13:21 +0100 1161227 http://www.medworm.com/index.php?rid=1148200&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F216274282%2F Some of you might recall my rant against Andy Grove, the former head honcho at Intel. While his bouts with Parkinsons and cancer are no laughing matter, I have to agree with Derek Lowe when he called Grove Rich, Famous, Smart and Wrong. Today, I noticed (via Techmeme) an article in Forbes, highlighting Andy Grove’s efforts in fighting Parkinson’s. His contributions, as well as people like Michael J. Fox are appreciated, especially when research dollars are so limited. However, the same articles points out some of the challenges. Not only is the drug approval process a time consuming, highly risky process, we often don’t know why a drug fails. Whether it is due to unforeseen safety or efficacy issues, dosage problems or any number of other reasons, the fact remains that b... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1148200 Mon, 14 Jan 2008 06:22:32 +0100 1148200 http://www.medworm.com/index.php?rid=1085974&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F12%2F11%2Fa_bad_assay_better_than_none.php Man, do we ever have a lot of assays in this business. Almost every drug development project has a long list of them, arranged in what we call a screening cascade. You check to make sure that your new molecule hits your protein target, then you try it on one or more living cell lines. There are assays to check its potency against related targets (some of which you may want, most of which you don’t), and assays to measure the properties of the compound itself, like how well it dissolves. Then it’s on to blood levels in animals, and finally to a disease model in some species or another. Not all these assays are of equal importance, naturally. And not all of them do what they’re supposed to do for you. Some processes are so poorly understood that we’re willing to try all sorts of stu... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1085974 Tue, 11 Dec 2007 13:27:34 +0100 1085974 http://www.medworm.com/index.php?rid=1055786&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F11%2F27%2Fthen_i_felt_like_some_watcher_of_the_skies_.php There’s an article in the latest Drug Discovery Today which takes off after the “Rule of Five” and its application to drug discovery. The author’s not saying anything that hasn’t been said before, though – first under the breath, then openly. But it bears repeating: ”The simplicity of these criteria to remove outlier molecules using software, made them very easy to implement. Thus, the Ro5 moved rapidly in the hierarchy of medicinal chemistry concepts from being a set of ‘alerting’ criteria in the minds of the medicinal chemists to a commandment engraved in the high altars of ‘do's’ and ‘don’ts’ of drug seekers. I am not a medical doctor nor am I a savvy drug-discoverer; I am just an apprentice. However, I suggest that ten years after the publication of the Ro5... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1055786 Wed, 28 Nov 2007 02:22:16 +0100 1055786 http://www.medworm.com/index.php?rid=1041883&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmalot%2F%7E3%2F188311442%2F Hired someone new and exciting? Promoted a rising star? Finally solved that hard-to-fill spot? Share the news with us and we’ll share with it others. That’s right. Send us your announcements and we’ll find a home for them. Don’t be shy. Everyone wants to know who is coming and going. Here are some of the latest moves… Watson Pharmaceuticals hired Mark Durand as senior vp and cfo; Polymedix appointed Bozena Korczak vp of drug development; Interbrand Wood Healthcare chose Jane Parker as ceo; APCO Worldwide hires Linda Distlerath, a former Merck heatlh policy vp, as sr vp; Wyeth tapped Andy Davidson, vp for internal audit, as principal corporate officer; Helix BioPharma says Don Segal remains ceo, but John Docherty becomes prez; CellCyte Genetics taps Tony Colasin as director of bus... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=1041883 Wed, 21 Nov 2007 14:53:35 +0100 1041883 http://www.medworm.com/index.php?rid=1031215&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F11%2F15%2Fquiz_time.php Do you have what it takes to run a med-chem project? Take this simple test and find out: 1. You have a compound with a suspicious reading in a hERG assay, indicating possible cardiovascular trouble later on. Do you: A) Brace yourself to scale up compound for dog cardiovascular tox (and brace the budget for paying for it), wondering if the animal group has gone through with that threat to switch to 60-kilo Irish wolfhounds. B) Brace yourself to start your SAR over, most of the way back from scratch, because your compound doesn’t fit anyone’s hERG model (what are the odds that you could miss them all?) and you have no idea of what to fix first, or C) Make a pest of yourself by pointing out all the historical compounds, now on the market and not causing trouble, that would have been ... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1031215 Fri, 16 Nov 2007 03:24:21 +0100 1031215 http://www.medworm.com/index.php?rid=1025411&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F184466887%2F Great post by Satish Nambisan on network-centric innovation, essentially looking outside for innovative ideas and partnering with external innovation networks. There are examples of such efforts in the life sciences, some of which have been covered on bbgm before, but they are the exception rather than the norm. However, it’s becoming apparent to me, and to other observers I am sure, that the tide is changing. One of these days I have to write my thesis on the future of the pharma industry, but for now, lets talk about the trend away from the two models that are common, the “not invented here” and the “lets buy it” model. Yes, the business of making drugs is getting distributed, taking advantage of the network. Slowly but surely that is going to become reality... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1025411 Wed, 14 Nov 2007 04:12:01 +0100 1025411 http://www.medworm.com/index.php?rid=1024398&cid=t_105099_150_f&fid=35777&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2FPharmalot%2F%7E3%2F184232310%2F Participation is low. While 16.9 percent of white docs participate as principal investigators, participation is lower among minorities - 14 percent of African-American docs, 10.8 percent of Hispanic docs and 9.6 percent of Asian docs, according to a study by the Tufts Center for the Study of Drug Development. As far as gender is concerned, 16.9 percent of male docs participate, but only 10.9 percent of female docs. In general, minority and female clinical investigators initiate far fewer clinical trials each year than white or male docs. “More than 70% of all physicians, regardless of race or gender, tell us they have a strong desire to participate in clinical research, but a number of factors are dissuading them from doing so,” says Ken Getz, a senior research fellow at the Tufts Cent... Pharmalot blogs http://www.medworm.com/rss/comments.php?id=1024398 Tue, 13 Nov 2007 18:11:31 +0100 1024398 http://www.medworm.com/index.php?rid=1019388&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F183261382%2F For long I have argued that we will really only be successful at drug design if we get a true grip on the physical basis of molecular recognition. Studies like the one mentioned in this post only convince me of that fact. It reminds me of some work we did in graduate school. We were doing site directed mutagenesis of the Violet Cone Pigment from Xenopus, trying to make the absorption wavelength shift to that of bovine rhodopsin. Some mutations on helix 2 (the helix we were focusing on) red-shifted the spectrum towards rhodopsin, others either did nothing or resulted in misfolded protein. Then we went on to doing concurrent mutations and even a chimera where we replaced the entire 2nd helix. Somewhat surprisingly the chimera had a wild type spectrum. Some of the models that we built suggest... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1019388 Sun, 11 Nov 2007 21:52:32 +0100 1019388 http://www.medworm.com/index.php?rid=1018381&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F182539608%2F I only bashed Andy Grove. Derek Lowe (for whom I voted in the weblog awards) has been on a tear, comparing the drug discovery business to Hollywood and to wildcatting for oil. Fantastic stuff!!! Oh, David Hamilton has a great take as well Technorati Tags: Andy Grove, Healthcare, Pharma, In the pipeline (Source: business|bytes|genes|molecules) business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=1018381 Sat, 10 Nov 2007 04:58:02 +0100 1018381 http://www.medworm.com/index.php?rid=1013513&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F11%2F07%2Freasons_to_be_different.php OK, now that we’ve thought over the Hollywood analogy to drug discovery, what about other industries? And if none of them fit, what is it about the pharmaceutical world that makes us so different? Wildcatting for oil has come up in the comments, and that’s a pretty good one. The ratio of dry holes to gushers is probably pretty similar, and using geology to figure out where to drill isn’t that much different than trying to figure out what screening hit to start a new drug program with. The lead time between discovering something and making money off of it (and the amount that has to be spent first) also lines up pretty closely. One difference, though, is that all oil wells yield the same thing (oil!), while drug discovery comes up with all sorts of things. The variety of our product... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1013513 Thu, 08 Nov 2007 02:57:14 +0100 1013513 http://www.medworm.com/index.php?rid=1007622&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F11%2F06%2Fandy_grove_rich_famous_smart_and_wrong.php So I see that Andy Grove, ex-Intel, is telling everyone that the drug industry could use some of that Moore's Law magic. I've noticed that people who spend a lot of time in the computer business often have an. . .interesting perspective on what constitutes progress in other fields, and we might as well appoint Grove the spokesman for their worldview: Q: In what way does the semiconductor industry offer lessons to pharma? A: I picked the semiconductor industry because it's the one I know; I spent 40 years in it, during which it became the foundation for all of electronics. It has done a bunch of unbelievable things, powering computers of increasing power and speed. But in the treatment of Parkinson's, we have gone from levodopa to levodopa. ALS [Lou Gehrig's disease] has no good treatment;... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1007622 Tue, 06 Nov 2007 13:26:30 +0100 1007622 http://www.medworm.com/index.php?rid=1003703&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F11%2F04%2Fnerve_lots_and_lots_of_nerve.php Sometimes I think that my chemical intuition is all haywire. Medicinal chemists, after they've seen several projects succeed and fail, accumulate a set of prejudices and opinions about what sorts of molecules are more likely to lead to good things (and what sorts are more likely to waste your time). Many of these are uncontroversial: no one, for example, is going to tell you to load up your molecule with plenty of guanidines or acid chlorides. But there's a big middle ground where the arguing starts. Sulfonamides - like 'em or hate 'em? How about ureas? Tetrazoles as carboxylic acid isosteres? All of these groups are found in marketed drugs, but you can find experienced medicinal chemists whose noses wrinkle at them, because they feel that too many such compounds fail to make them worthwh... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=1003703 Mon, 05 Nov 2007 01:43:14 +0100 1003703 http://www.medworm.com/index.php?rid=926257&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F165044868%2F Thomas Goetz asks, Is pharmacogenomics for real?. I left a long comment with the post, so I won’t repeat myself here, but I did want to add a few additional words. Pharmacogenomics is for real, but like all things omic, the hype is always amplified. One thing to note is that it takes a long time for a drug to come on to the market, so the impact of pharmacogenomics is still small when it comes to drugs on the market. That said we are still some ways away from seeing a significant number of drugs being released with companion diagnostics (which is what I believe Thomas was curious about). There are several reasons for that. Some are 1. We don’t quite understand which biomarkers are the right ones. There are multiple prognostic tests for breast cancer. Which one is more robust? I... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=926257 Thu, 04 Oct 2007 05:25:08 +0100 926257 http://www.medworm.com/index.php?rid=894221&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F160445572%2F In a post some months ago, I had used the following quote Data finds data, then people find people I had mentioned that the originator of the idea that “data finds data” was Jeff Jonas. I had the pleasure of meeting Jeff at Scifoo, where we spent a brief amount of time talking about his theories on data and the applications in bioinformatics. I’ve spent some time in recent days devouring his blog. One of the statements from there that really made an impact on me Sensing importance across a sea of dynamic systems with constantly changing data requires the accumulation and persistence of context. This statement has a lot of applications in the life sciences. Let’s take the example of a project at a biotech or pharma company. The project contains information from m... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=894221 Mon, 24 Sep 2007 04:12:39 +0100 894221 http://www.medworm.com/index.php?rid=867457&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F09%2F12%2Fdrugs_from_where.php The mention of tropical diseases here the other day turns out to be timely, since the latest Nature has several articles on various ways for industry and academia to partner on attacking these. Some adjustments are needed every time you try this sort of thing, naturally. I particularly enjoyed this article. Here’s a sample: “. . .translational research requires skills and a culture that universities typically lack, says Victoria Hale, chief executive of the non-profit drug company the Institute for OneWorld Health in San Francisco, California, which is developing drugs for visceral leishmaniasis, malaria and Chagas' disease. Academic institutions are often naive about what it takes to develop a drug, she says, and much basic research is therefore unusable. That's because few universit... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=867457 Thu, 13 Sep 2007 01:27:11 +0100 867457 http://www.medworm.com/index.php?rid=831100&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F08%2F30%2Felbow_room.php I hope that in decades to come that our current drugs look as crude as I think they will. For all of our knowledge and all our equipment, we still don't have much of an idea of what we're doing around this industry, not compared to the sum of what there is to know. Most of our drugs (by "most", I mean way over 95%) bind to proteins. And that's fine, as far as it goes, because proteins sure are important things. We love them because many of them have pockets and cavities that fit small molecules, of course, giving us a tremendous leg up. But it's not that we've figured out how to attack them reliably, though, when you consider that there are many entire classes that have never been successfully targeted (phosphatases, to pick an outstanding example). Once you get out of the small-molecule... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=831100 Thu, 30 Aug 2007 11:09:01 +0100 831100 http://www.medworm.com/index.php?rid=828534&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F08%2F28%2Flike_clockwork.php There are a lot of drug development issues that people outside the field (and beginning medicinal chemists) don't think about. A significant one that sounds trivial is how often your wonder drug is going to be taken. Once a day is the standard, and it's generally what we shoot for unless there's some reason to associate the drug with meals, sleep/wake cycles, or the like. People can remember to take something once a day - well, they remember it better than most of the other dosing schedules, anyway. That's why you actually want your compounds to be metabolized and cleared - everything has to be ready for the next dose tomorrow. If your compound has a long half-life in the body after dosing, you'll step on the tail end of the last dose and you can see gradual accumulation of the drug in p... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=828534 Wed, 29 Aug 2007 02:37:32 +0100 828534 http://www.medworm.com/index.php?rid=783898&cid=t_105099_87_f&fid=34867&url=http%3A%2F%2Fwww.thediabetesblog.com%2F2007%2F08%2F07%2Ffunding-boost-for-insulin-gel-caps%2F Filed under: Research, Products, SupportThere's a story running on CNN Money about the progress of Oramed Pharmaceuticals' insulin capsule, which is currently under development. The capsule, taken orally, could provide a more convenient way for diabetics to get insulin than through shots. And popping a gel cap would, needless to say, also be more convenient than toting and blowing on one of those big old clunky Exubera inhalers.In the quest to get its product to market, Oramed needs cash, and lots of it. Answering the call, a combination of private investors are putting up more than two million dollars in financing for the Israel-based company.It's hoped the money will help to propel the insulin capsule through completion of Phase 1 (drug safety) trials by the middle of next year. Said Ora... The Diabetes Blog blogs http://www.medworm.com/rss/comments.php?id=783898 Tue, 07 Aug 2007 04:00:00 +0100 783898 http://www.medworm.com/index.php?rid=784111&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F08%2F06%2Fhere_fix_this_would_you.php As I mentioned the other day, drug companies manage the shift from med-chem to process in a lot of different ways. (For those outside the industry, the medicinal chemists are focused on making relatively small amounts of a lot of different compounds, while the process labs concentrate on making large amounts of a few). Some places allow the med-chem labs to use whatever wild chemistry they can think up, on the theory that if a compound is really interesting the process labs will find a way to make it on scale. Others strongly discourage some kinds of chemistry (particularly nasty solvents and reagents), since real problems can occur if a lead compound comes from that sort of background. I incline more to the latter. Perhaps it's just a dislike of leaving messes for other people to clean u... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=784111 Tue, 07 Aug 2007 02:19:07 +0100 784111 http://www.medworm.com/index.php?rid=763186&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F07%2F27%2Fyou_discover_it_we_sell_it_deal.php There was a comment to the previous post which asked an interesting question: if you look at the best-selling drugs in the portfolios of the major companies, what percentage of them were developed in-house? I'm sure that someone has already done this analysis, but I haven't been able to lay my hands on it. But in some cases it's a rather embarassing figure - Pfizer, for example, which brings up the question of how you define "in-house" when the house keeps expanding. The rigorous definition - a project (and chemical matter) that started inside the company and went all the way to market - is probably the way to go. A drug that came about through buying a compound, a target, or a whole company doesn't qualify. It's impossible to talk about this without someone bringing up the idea of a vir... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=763186 Fri, 27 Jul 2007 11:53:44 +0100 763186 http://www.medworm.com/index.php?rid=758082&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F07%2F25%2Ffrom_the_sequencer_to_the_drugstore.php A science writer who's read this blog for some time asked me a question which I thought I'd throw out to the readership. I was, in yesterday's post, making reference through gritted teeth to the amount of money the drug industry spent on genomic approaches. So here's the question, verbatim: "What drugs, if any, have been developed thanks in large part to insights gleaned from the human genome project?" I don't think we're going to have to use many fingers, personally, given what I've seen. The "in large part" clause will take care of a lot of tangential cases that have been claimed mostly for PR purposes. There may be some dispute about the word "developed", since it could still be early for something to be hitting the market from the time of the Human Genome Project. Let's take that to m... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=758082 Wed, 25 Jul 2007 23:39:20 +0100 758082 http://www.medworm.com/index.php?rid=751824&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F07%2F23%2Fdeactivation_after_all.php Four years ago I wrote about an unusual Roche diabetes compound targeting glucokinase. The odd thing about it was that it made the enzyme more active, which is something you can only rarely hope to do. Enzymes generally run near the top of their specs, unless there's some built-in switch that keeps them damped down until they're needed. That's often phosphorylation, but another trick inside the cell is to keep the concentrations of substrate low (or the concentrations of some inhibitor high). But once they go, they usually go about as fast as they can. This glucokinase example is still about the only one I can think of in drug development, and it's had a fair amount of attention over the years. Maybe I should switch the tense, though, because reader Daniel H. has informed me that Roche se... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=751824 Tue, 24 Jul 2007 00:35:25 +0100 751824 http://www.medworm.com/index.php?rid=750321&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F07%2F22%2Fa_farewell_to_tin.php I was browsing through the posts at Totally Synthetic, which is now my substitute for looking at total synthesis papers in the primary literature, and came across this question: "However, this brings me to a point of consideration - why are Stille coupling (reactions) more common in academic publications, and Suzuki more so in an industrial/commercial context?" (For the non-chemists in the audience, these two reactions are ways to skin what is basically the same cat - forming carbon-carbon bonds on a particular class of starting materials). And this is one of those questions with a one-word answer, and in this case you can pick your word. Either "tin" or "toxic" would work just fine. The Suzuki uses boronic acids or esters, which are generally water-soluble and nonpoisonous. The Stille r... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=750321 Mon, 23 Jul 2007 01:21:42 +0100 750321 http://www.medworm.com/index.php?rid=749689&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F136215499%2F This post was going to be a rant, but since it took me a while to get to a computer, wiser heads prevailed. I am a regular follower of Chris Pirillo’s activities. He’s a smart dude, who says what’s on his mind. Yesterday, I read a post he wrote on pharma (it’s part of a series actually). My first reaction was to respond with a rant of my own, but then I started thinking a bit about a few things. It’s no secret that the healthcare and pharma industry are facing a PR crisis. The healthcare system in the US has serious issues. Some might argue that it is completely broken. But what about the pharmaceutical industry? For a minute or two or three, lets look at it independently of the healthcare system. Why does the healthcare industry have the reputation that it do... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=749689 Sun, 22 Jul 2007 15:32:23 +0100 749689 http://www.medworm.com/index.php?rid=730391&cid=t_105099_150_f&fid=34889&url=http%3A%2F%2Fpharmamkting.blogspot.com%2F2007%2F07%2Fwhy-grow-your-own-drugs-when-you-can.html According to a report on Pharmalot, Merck is expanding its move into oncology by striking a deal with Ariad Pharmaceuticals to buy the cancer drug AP23573 mTOR from Aiad Pharmaceuticals."Here's the deal: Ariad will receive an initial payment of $75 million, up to $452 million more in milestone payments based on the successful development in different cancer indications, and up to $200 million more based on sales thresholds. Ariad can also expect at least $200 million in estimated contributions by Merck to global development, and up to $200 million in repayable advances from Merck to cover its share of global-development costs, after Ariad has paid $150 million of those costs. (See "Merck Invests $1B In A Cancer Pill")So this is what the pharma industry means when it says it costs $1 Billio... Pharma Marketing Blog blogs http://www.medworm.com/rss/comments.php?id=730391 Thu, 12 Jul 2007 17:20:00 +0100 730391 http://www.medworm.com/index.php?rid=693271&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F127582394%2F At the recent DIA Annual Meeting the top subject, or so it appeared, on everyone’s minds was safety. Adverse event reporting, pharmacovigilance, etc were buzzwords that one didn’t have to look far to hear. If someone asked you, as a life scientist, what the top priorities in healthcare should be, what would you say? In my opinion, we need to be thinking seriously about how we can change drug development paradigms in the context of all the information that we have to try and make sure that attrition rates are decreased dramatically. Current efforts are just extensions of what we’ve been doing for years, and they are not working. Safety would be right up there, along with trying to rebuild public trust. Technorati Tags: Healthcare, Adverse Events, DIA, Drug Development (Sou... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=693271 Sun, 24 Jun 2007 21:11:37 +0100 693271 http://www.medworm.com/index.php?rid=728636&cid=t_105099_149_f&fid=35776&url=http%3A%2F%2Fpipeline.corante.com%2Farchives%2F2007%2F06%2F20%2Fbigger_tougher_longer_or_not.php Here's a question that was posed to me an an e-mail, which I thought I'd open up to everyone. Is the perception accurate that new clinical candidates (and new approved drugs) are getting more complex? And if so, are the processes used to make them getting longer and more complicated at the same rate? I've seen the charts on the increasing molecular weight, etc., of candidates over the years, which is one surrogate for complexity. The relentless trend toward single enantiomers is probably a driver, too, so I'm certainly willing to credit the idea that the molecules are getting gradually woolier. What I'm wondering, though, is whether this is being reflected in the process work. Has anyone seen any statistics on "average number of chemical steps" or the like? My guess is that it's been inc... In the Pipeline blogs http://www.medworm.com/rss/comments.php?id=728636 Wed, 20 Jun 2007 14:19:42 +0100 728636 http://www.medworm.com/index.php?rid=728723&cid=t_105099_150_f&fid=35781&url=http%3A%2F%2Fwww.qdinformation.com%2Fqdisblog%2F2007%2F03%2F28%2Freplidyne-defines-development-plan-for-faropenem%2F Replidyne is continuing to refine its phase III efforts for the antibiotic faropenem. Replidyne Defines Preliminary Phase III Development Plan for Faropenem: Financial News - Yahoo! Finance: This new antibiotic may be the first to be approved under the FDA’s new community standards for antibiotics. Technorati Tags: Faropenem, Replidyne Copyright © 2007 QDIS Blog. This Feed is for personal non-commercial use only. If you are not reading this material in your news aggregator, the site you are looking at is guilty of copyright infringement. Please contact legal@qdinformation.com so we can take action immediately.Plugin by Taragana (Source: QDIS Blog) QDIS Blog blogs http://www.medworm.com/rss/comments.php?id=728723 Thu, 29 Mar 2007 01:35:08 +0100 728723 http://www.medworm.com/index.php?rid=486919&cid=t_105099_132_f&fid=35011&url=http%3A%2F%2Ffeeds.feedburner.com%2F%7Er%2Fmndoci%2F%7E3%2F102643126%2F A new medicinal chemistry blog has an interesting post about “idiosyncratic” drug reactions, adverse reactions that occur in a small set of patients. For any number of reasons, trying to get a handle on unpredictable ADRs in small patient subpopulations is critical for the pharmaceutical industry. I am no authority on such ADRs and suggest reading the original post for more information, including references and the authors views. Currently, idiosyncratic ADRs are not predictable since their mechanisms are not well understood. This is where I believe that translational research is going to play a strong role. Can we identify potential biomarkers (either metabolic markers or genotypes or anything else) that can help identify potential patient subpopulations that might suffer from... business|bytes|genes|molecules blogs http://www.medworm.com/rss/comments.php?id=486919 Sun, 18 Mar 2007 20:06:20 +0100 486919 http://www.medworm.com/index.php?rid=728733&cid=t_105099_150_f&fid=35781&url=http%3A%2F%2Fwww.qdinformation.com%2Fqdisblog%2F2007%2F03%2F15%2Fdrug-safety-data-from-clinical-trials%2F It use to be that major pharma companies did not want to share safety data from clinical trials because they considered the information proprietary. PharmaLive: Taking the Wraps Off Drug Safety Data from Clinical Trials : There has been much talk recently about changing that. Some companies have said they will start their own database however, having many different database with differing information I don’t feel would be productive. I also don’t think a voluntary program run by a pharma group would be the best solution either. I’m not sure what is the best but think that in the next five to six years you will see some sort of database covering multiple companies. Here are some recommendations from the article in Health Affairs in the March/April 2007 issue. The authors ... QDIS Blog blogs http://www.medworm.com/rss/comments.php?id=728733 Thu, 15 Mar 2007 15:01:13 +0100 728733