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
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Technorati Tags: biogenerics, biosimilars

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

FDA deny drug application from Advancis - Washington Business Journal: :

What is very interesting to me is that Advancis does not have a press release on this on their website. The last press release they have is dated Jan, 12 2007. This day and age, it is amazing to me that companies don’t react quickly to these sorts of situations. It’s been two weeks since this happened with no word from the company on their website. I understand that time is needed to form a response but something should be immediately announced.

Their Amoxicillin PULSYS once daily dosing is the product concerned and according to the company they were surprised just like Pharmacyclics that I posted about previously at the FDA’s response. The FDA, according to the company, is concerned about how they plan to scale up their manufacturing process to make bulk quantities. Previously, the company had failed some phase III clinical trials which had to be repeated and then had to re-file the NDA in Dec 2006.

I’m wondering if this means the companies are not really listening to the FDA or if the FDA is changing their mind midstream. While this may not seem to be much of difference it could have major implications for other companies getting ready to file NDAs. If the FDA is starting to crack down and not even accept applications, then the industry needs to be much more careful about how they prepare their filings. If on the other hand, these two companies just weren’t really listening and picking up on the nuances from the FDA then it may not have much of an effect on other companies.

I do know from personal experience that you have to be very careful in the questions you ask the FDA. Many times at end of phase x meetings, you submit questions in writing ahead of time and depending on exactly how those questions are worded, you may get different answers. I know of some companies that will only ask yes or no questions and try to word the question so as to get the answer they desire instead of asking questions to really learn what the FDA thinking is on a given set of circumstances. I have always felt this was a mistake. Early on, it is vitally important to ask open ended questions before too much time and money is spent going down a regulatory or development route that may lead to failure at a late stage when it is very costly.

Technorati Tags: Advancis, FDA, amoxicillin pulsys

Roche revamps R&D for speed:

An import part of the article is in the last paragraph. GlaxoSmithkline reorganized their research into seven Centres of Excellence for Drug Discovery years ago and I don’t know that it has increased their overall productivity. It may gets more drugs into development, but the more important issue of making sure the ones that do go into development have the greatest possible probability of success.

I’ve seen this before and I don’t have much faith in these “reorganizations”. Inevitably, these sorts of moves don’t make major contributions to the bottom line and sometimes actually make matters worse. I personally think that the culture and huge bureaucracies are more to blame for the lack of research results. That isn’t to say re-orgs can’t make thing better, that can be. I just think too many times they don’t pay off.

I’ve also said that just moving the bottlenecks of development from one place to another is not the answer. The bottlenecks need to be removed from the system entirely, rather than just moved from place to place without increasing the overall output.

Technorati Tags: GlaxoSmithKline, Roche

PharmaLive: Anacor Signs Worldwide Exclusive License Agreement With Schering-Plough for AN2690, a New Topical Anti-Fungal Treatment :

What is interesting is the structure of AN2690 shown below.

Not many drugs have a boron atom in them and so it is very interesting. Anacor claims that this compound inhibits a validated drug target and works in a totally unique and unprecedented way.

One of the main problems with fungus of the nail bed is penetration to get at the infection deep down. Other treatments are oral medications and therefore work systemically. Also, Lamsil as well as Sporanox (itraconazole) capsules have had an FDA public health advisory issued warning physicians about adverse hepatic events and an association with congestive heart failure associated with both of these drugs. Definitely not something you want to risk for a simple thickened fingernail of toenail.

Topicals haven’t had a lot of success in this area so it will be interesting to see how this works. Anacor claims AN2690 penetrates 200 times better than the only other approved product. There is definitely interest in this since the market for onychomycosis is a $1.5 billion dollar market.

Anacor also has piblished some data on this compound.
Microbiological Activity Of AN2690, A New Antifungal Agent (pdf)

Other Resources
ANACOR SIGNS WORLDWIDE EXCLUSIVE LICENSE AGREEMENT WITH SCHERING-PLOUGH FOR AN2690, A NEW TOPICAL ANTI-FUNGAL TREATMENT
Schering-Plough Cites Today’s Anacor Agreement as Latest in Series of Deals
T

Technorati Tags: AN2690, Anacor, pharmaceutical deals, anti-fungal, Schering-Plough

Pharmaceuticals | Billion dollar pills | Economist.com

The article talks about many points I’ve made here before and even talks about bringing together scientists in one center and focusing on just a few therapeutic areas. It is an interesting read although think it still falls short of outlining what needs to be changed in the pharmaceutical industry.

One of the premises of the article is that the pharmaceutical industry tries to do it all and does many things in-house. The authors suggest more out-sourcing (although that terms is not used) and to concentrate on just a few strengths. The author uses the term “disaggreagted”. While this may work to some extent, I don’t think it will ever be as prevalent as say the automobile industry. While I do believe there are things the pharmaceutical industry can learn from other industries about how to become more efficient, I think you need to be careful and closely scrutinize the ideas before trying to apply them to pharmaceuticals. All ideas that work in other industry may not be applicable to pharmaceuticals.

One of the major problems from my perspective is still the blockbuster drug mentality. All of the things outlined in the article are still geared towards finding the billion dollar a year drug. This mentality is what has brought on the current situation for big pharma and will continue to be a major issue in the next 4-5 years. By this, I mean anytime the bulk of a company’s revenues are from one or two products, they are in a precarious situation. It would be much better in my view to have three or four $500 million products rather than a single $1 billion. They have basically put all the eggs into one basket. Too many times, projects that have good possibility are not pursued because they don’t meet this arbitrary mark of a billion dollar a year in sales. I would much rather have a company with four or five products generating hundreds of millions of dollars in sales that expire intermittently over many years than one product with a billion dollar a year in sales that expires in a few years.

Here are the top 20 pharmaceuticals companies and the percentage of pharmaceutical revenues generated by their top two selling drugs according to 2005 data. This data is generated from the Top 20 Pharmaceutical Companies article published last year in Contract Pharma.

Pfizer 38% from Lipitor and Norvasc
Sanofi-Aventis 18% from Plavix and Lovenox (increases to 25% if you include Taxotere, its third best selling drug)
GlaxoSmithKline 23% from Advair and Avendia
AstraZeneca 31% from Nexium and Seroquel
Merck 35% from Zocor and Fosamax
Novarits 29% from Diovan and Gleevec
Hoffman-La Roche 31% from Rituxan and Epogin
Bristol-Myers Squibb 40% from Plavix and Pravachol
Wyeth 36% from Effexor and Protonix
Eli Lilly 40% from Zyprexa and Gemzar
Abbott Labs 20% from Humira and Mobic
Boehringer-Ingelheim 25% from Spiriva and Mobic
Takeda Pharmaceuticals 40% from Actos and Prevacid
Scheringer-Plough 24% from Vytorin and Remicade
Astellas Pharma 28% from Prograf and Harnal (increases to 39% if you include Lipitor its third best selling drug)
Daiichi-Sankyo figures not available
Novo Nordisk 66% from insulin and insulin related analogs
Eisai 51% from Aricept and Aciphex
Bayer 27% from Ascensia and Kogenate

As you can see it ranges from a low of 18% for Sanofi-Aventis to a high of 66% for Novo Nordisk. The Novo Nordisk may be an unfair number since they lump insulin products and insulin analogs as their top two drugs and these are really aggreagates. However, the point is that for all the top pharmaceuticals, a large portion of their revenues are generated from only a few products.

Many of these either have patents expiring or have had bad press recently which combined with the decreasing number of potential products will likely lead to a desperate situation for the foreseeable future..

Technorati Tags: pharma pipelines, pharma stats, pharma worldwide markets

Faropenem Phase III Clinical Trial Stopped to Consider Exclusion of Ketek Comparator

Replidyn has already received a non-approvable from the FDA back in Oct 2006.

U.S. Food and Drug Administration Issues Non-Approvable Letter for Faropenem

What is somewhat interesting in this respect is that it seems to reflect a change in FDA policy regarding superiority studies in particular with antibiotics and especially for the AECB indication.. In the past, the FDA has not required this for antibiotics and the studies done on Faropenem were non-inferiority designs. Replidyne may be getting caught in the changes where the FDA is now looking into placebo controlled studies for antibiotics. This new study which is being stopped to consider exclusion of Ketek, was planned as a placebo controlled superiority study. However, now the question is do they continue with the comparator Ketek. I think it likely that they will exclude the Ketek arm and likely choose another comparator. This means even more delays.

I do feel for Replidyne and think they have gotten caught up in the changing climate and this is likely not their fault. My concern though is that it may mean even more companies do not get into development of anti-infectives, an area of vital need now in my opinion.

Other Resources
Faropenem - Wikipedia, the free encyclopedia
Replidyne (page on Faropenem Medoxomil)Zoom structure
CID 636379 — PubChem Compound Summary

Technorati Tags: Faropenem, Ketek, Replidyne, telithromycin

Glaxo Goes Head-To-Head With Merck - Forbes.com

GlaxoSmithKline is definitely behind in this regard; Merck’s Gardasil is already approved and on its way towards $700 million in sales it first year. GSK on the other hand won’t even submit an NDA until at earliest 2009 and so will be at least three years behind.

Another problem is that the proposed study is only 1,000 patients and some, including myself, wonder if this will even allow you to see if there is a difference. Also GSK is taking a shortcut and making the argument that testing the response generated by the immune system due to the vaccine will be an indicator that the vaccine works better and longer. This has not been proven to be the case and the FDA in general frowns on such approaches. It will definitely be an uphill battle and I see the likely outcome being the FDA asking for longer term data on how well it protects against cervical cancer and precancerous lesions. This would set back GSK by years. It is a risky gambit.

Many consider this risky and in general, the pharmaceutical industry avoids, at all cost, comparing their drug directly against a competitors. The main exception to this is in anticancer drugs where drugs are always tested against a comparator since it is consider unethical to not treat those affected. The choice of comparator, when it is used, is questionable. Many times the drug chosen as competitor is not the best in the field and few experts would suggest this drug as a first choice for there patients.

I often wonder and have actually asked in meetings why not test against the best in class. Many times upper level management touts their drug as a breakthrough in treatment of a disease and over-hype it to the media and the public. However, in private internal meetings, they want to choose a comparator (if used at all) that gives them the best chance of a positive outcome. I say if they have such confidence that they express in public why is it that behind closed doors they do everything they can to tilt the field in their favor. If they have confidence in public, why does that confidence evaporate in private planning meetings?

Technorati Tags: cancer vaccine, GlaxoSmithKline, Merck, cervical cancer, vaccine

Bristol-Myers, AstraZeneca in Drug Pact - Forbes.com:

Details are that AstraZeneca will pay BMS $100 million upfront and BMS could earn up to another $650 million in development milestones and then another $300 million in sales milestones. This makes the deal worth potentially over $1 billion dollars!!

It is interesting to look at why this deal may have been done. BMS evidently doesn’t feel they could go it alone on this or they would have. They get AstraZeneca to pick up the bulk of the development costs through 2009 and expenses after that being shared. BMS will make the drug and book sales. Also any future compounds discovered by either company would be included under this partnership.

To me this looks like the first step in a possible future merger. If the drugs are blockbusters then it might make sense in the future for them to merge rather than continue the partnership. Only time will tell. Saxagliptin is in late stage clinical trials whereas dapagliflozin is somewhere in the middle of the process, so it will be several years before we’ll know how this plays out. My best guess; if both drugs are approved and are blockbusters then the companies will likely merger sometime after 2010.

Technorati Tags: AstraZeneca, Bristol-Myers Squibb, dapagliflozin, diabetes treatment, drug development, pharmaceutical deals, saxagliptin

Telik cancer drug fails trials; stock plummets - Yahoo! News
MercuryNews.com | 12/27/2006 | Telik stock takes a 71% hit

It is unclear why this occurred but the company claims that some patients who were dismissed from the study early may have been part of it. As usual the company is looking at the data to see if anything can be learned and to see if the drug can be possibly salvaged.

One of the things to keep in mind with cancer drugs is that unlike other drug categories, with cancer you have to compare against the standard of care. This means you are comparing your drug against a proven drug for a given indication.

I should also add that it wasn’t just one study; it was three phase III registration trials in ovarian and lung cancer as well as in combination with another drug for ovarian cancer. The fact that all three trials failed to meet its endpoints seems to point to the fact that the drug may not be working and should be discontinued.

One of the problems with small companies is their hesitancy to kill drugs early on. Too many times in my experience they throw good money after bad by trying to keep a project alive when it should have been killed a long time ago. This is especially true if the company only has a single compound in their pipeline. Fortunately, Telik has another drug in its pipeline called Telintra (TLK199) although it is in early stage trials.

It will be interesting to keep an eye on Telintra since this is the second drug to come out of their discovery platform called TRAP (target-related affinity profiling). If a second drug fails, it may point to the fact that this technology isn’t worthwhile.

Other Resources

TELIK REPORTS PRELIMINARY RESULTS ON ASSIST-1, ASSIST-2 AND ASSIST-3 PHASE 3 CLINICAL TRIALS
Yahoo! News Search Results for telik
telik - Google News
Google Blog Search: telik

Technorati Tags: Telcyta, Telik

FDA Proposes Broadening Access to Drugs - New York Times

I am a backer of allowing greater access to experimental drugs but feel that the key in this is the word “appropriate”. While no one would object to this with regard to life threatening conditions such as cancer it is unclear how other situations would be dealt with. One of the point in the proposed rule states that:

modernize applicable regulations to include all circumstances under which access to experimental drugs is permitted.

This seems to be a little overly optimistic to me. I find it hard to believe they could define ALL CIRCUMSTANCES in which this may be appropriate. What about someone who has a respiratory ailment that makes breathing difficult and they have tried all approved therapies without positive results? Maybe it keeps them from being mobile and getting out of their home. If there is an experimental drug that could significantly improve their quality of life would this be allowed? The question basically boils down to what is appropriate and this could indeed vary with regard to aliment and even for given patients having a certain condition. I think rather than trying to state all conditions it might be better to define the process allowing for the use of experimental drugs.

One of my other concerns in this involves the fact that our society today seems to be very litigious. Seems anytime something goes wrong, we look for someone else to hold responsible or to sue. I firmly believe that if a company deliberately withholds information concerning dangers or concerns then they should be held liable. However, in the case of an experimental drug, little may be known and opening it to what use to be called compassionate use may be opening a can of words. I firmly believe individuals should be held accountable for their decisions provided it is an informed decision. I’m not sure how this would be worked out, but I’m sure that this will be an item for discussion.

Technorati Tags: drug safety, FDA, experimental drugs

Process Engineering | R&D takes the fast track | Chemical Processing

Many of these articles focus on automated systems working overnight and lowering labor costs. While I don’t dispute that, I think there needs to be more thought put into what you can learn from this and how it can be used effectively. In some ways, it reminds me of when desktop publishing first came to personal computers and people used dozens of fonts, formatting and colors simply because they were could. After a while, people realized that using these indiscriminately just because you could, did not result in better communication of ideas. The same holds true with automated high throughput experimentation. Just because you can perform thousands of experiments in a week doesn’t mean you should or that you are getting the best answer. Doing 1,000 reactions in two weeks isn’t as productive as 200 carefully chosen and designed experiments done in three days.

Here are my basic points.

1. There is a need to work smarter not faster.
2. Better use needs to be made of the data generated.

First, I am a firm believer in spending time up front thinking about the problem before starting to do experimentation. This avoids the “Ready, Fire Aim” mentality that seems to be so pervasive in some R&D departments. I understand this tendency and fell into that trap myself early in my career. However, taking the time to think through the possible variables that could have an impact is a worthwhile exercise.

One of the most important aspects of this thinking ahead before performing experiments involves, design of experiments. This is a way of running reactions to get the greatest amount of information from the smallest number of experiments. While it may not be as imperative as it was in the past to run a small number of experiments, it still is valuable to run the best set of experiments possible. Using advanced software, it is possible to get the best set of experiments regardless of how many variables there may be or whether or not those variables are discrete in nature (such as which catalyst to use) or non-continueous (where only a given set of of conditions can be ran). I would point out that QD Information Services has the capability to design experiments specifically for your situation.

The second point involves better use of the data generated. I have come across too many situations where the approach was to run hundred or thousands of experiments and then sort those in a spreadsheet and go forward with the top one or two choices. At a major process development conference last year, one of the top ten pharmaceutical process development directors made a point of listing all the reactions they had run to find the “best results”. At the end I stood up and asked what they did with the data and got the reply that basically they had solved the problem and moved on to the next problem.

The problems with this approach is it does not take advantage of all the experiments that have been performed. Why invest the amount of time into setting up that many experiments and collect that much data and not try to get as much information as possible out of it? Also, how do you know you have found the “best answer”? Too many times, it is settling for what is acceptable instead of what is best. This leads to openings for your competitors to come in, find the true optimum and possibly patenting that and preventing you from using the best possible conditions.

The best approach is to design the experiments up front but even if that doesn’t occur it is possible to do data mining and possibly find meaning in the data. It continues to amaze me the number of large and mid-sized pharmaceutical companies that don’t take advantage of all the data generated to get the most out of their investment. And too many times, the answer I get is they don’t have time to do more and must move on to the next problem. I often offer to do this data mining for them but they still fail to see any value in this activity. To me, I think this is poor decision making and not getting the most out of your investment and it could come back to haunt you.

I just want to remind folks that QD Information Services can help in these sorts of situation so if you have a need for this, please feel free to contact me and I’ll help you understand how you can get the most out of your data.

Technorati Tags: data mining, design of experiments, high throughput

It is always a pleasure to talk with someone about this topic and hopefully people find it helpful in understanding the world of pharmaceuticals. We talked about drug pricing, Medicare, patents and the world wide situation with regard to pharmaceuticals. He also interviews a friend os his who works for a small biotech company and I always like to hear what others have to say about this topic.

Give it a listen and please feel free to contribute to the conversation on his blog or to leave me comments here.

Technorati Tags: pharmaceutical companies, podcast, prescription drugs

Benefited Patients with Type 2 Diabetes by Improving Blood Sugar Control - FierceBiotech:

Recently released data showed that Rimonabant a cannabinoid type 1 (CB1) receptor blocker helped patients control their sugar levels. It should be noted that these were type 2 patients who were not undergoing other treatments. THe A1C levels(a long term measure of how well blood sugar is controlled) showed small but significant decreases when treated with 20 mg of Rimonabant per day.

It will be interesting to see where this goes since the FDA issued an approvable letter and Sanofi gave their response. There really isn’t much there just that they will work closely with the FDA on its future development.

My best guess is this won’t have any impact on the questions the FDA asked since this study was likely underway long before the Feb approvable letter from the FDA.

Technorati Tags: Acomplia, Rimonabant, Sanofi-Aventis

Pfizer scraps cholesterol drug:

It’s chemical structure is shown below.

Pfizer has been working on this for about 15 years and may have sank more then $800 million into its development. The latest trend in cholesterol treatment is to not only lower overall cholesterol but to increase the so called “good cholesterol” (HDL). THere are several companies looking into this in some way. One of these that I have mentioned previously is Niacin (vitamin B3). It was used quite a bite before the statin drugs but had the side effect of causing flushing. Now several companies including Merck are working on drugs that would block this flushing. The drug they are working on is called MK-0524.

MSD’s Investigational MK-0524 Significantly Reduced Flushing Caused By Extended-Release Niacin in Phase II Study: Financial News - Yahoo! Finance

I found the structure in the literature and it is shown below.

Another article in Forbes talks a little more about Pfizer’s failure.

Behind Pfizer’s Failure - Forbes.com

They mention that this won’t sink Pfizer but it certainly will be painful. It will also be interesting to see how it shakes out with other companies working on similar drugs.

Other Resources

Yahoo! News Search Results for torcetrapib
torcetrapib - Google News
Google Blog Search: Torcetrapib

Technorati Tags: cholesterol, Pfizer, Torcetrapib

United Press International - Health Business - Analysis: FDA approving more drugs:

The report states that September and October were strong and there have been 83 approvals putting it in line with 2004 results. However, this may be temporary and not a long term trend. I think the lack of a lead and the possibility of even more legislation regarding drug safety will likely slow down the process.

I personally think the low-lying fruit has been picked over throughly and now there needs to be more validation of potential drug targets in order to facilitate research and allow for more potential drugs to be developed. Until more valid targets are discovered, I think the rate of drug development will continue to be sluggish.

United Press International - Health Business - Analysis: CROs may prosper under Democrats:

Their reasoning confuses me. James Kumpel, an analyst with Friedman, Billings and Ramsey states that these organizations will thrive since safety is likely to be a focus. They then mention three companies; PPDI, Covance and eResearchTechnology. What I fail to understand is how using a 3rd party contractor makes the drug development process inherently safer? I understand that if electronic filing of clinical data is required that some companies may benefit but I don’t see how safety is improved. The reasoning is vague at best in this article and it may be that these investment firms have a interest in seeing these companies do well.

I’ll have another post later on my general ideas of how the new congress may effect the pharmaceutical industry.

Technorati Tags: Congress, drug safety

A world of outsourcing awaits – part III drug manufacturing:

The article basically states that there is over-capacity in the active pharmaceutical ingredients (API) mainly due to increasing capacity in India and China as well as a reduction in drug pipelines as well. I would add that there seems to be s shift from classical small molecules to either more involved new chemical entities (NCE’s) or biologics. Since biologics have much higher prices and better profit margins, more and more major pharmaceutical companies are expanding into biotech manly by acquisitions.

However, the area of final product (FP) or finish fill operations, seems to be going well with continued growth. Another area seeing growth are the so-called contract biomanunufacturing organizations (CMBOs). This area will be interesting to watch in the coming years and it may end up that these operations are more about growing to the point of being an attractive acquisition than in long term survival. I could be wrong, but that is what is currently looks like to me.

Technorati Tags: outsourcing

Bird Flu Vaccine May Hit Many Strains - washingtonpost.com:

The key point appears to be that the specific strain this vaccine was based on from Vietnam, shows cross protection against other strain of the H5N1 from other countries. While this is interesting, it does not guarantee immunity against all H5N1 strains. Indeed it is good to see and emphasize that the researchers state it is very early and they still don’t know enough to make blanket statements about cross protection.

Another point made in the article is that stockpiling vaccine may be an effective approach. However, it is still risky since it is unknown if the next pandemic will even be H5 based. It might very well end up that we are concentrating on the wrong virus; it is impossible to predict which virus could lead to the next pandemic.

Other Resources

• InteliHealth: Bird Flu Vaccine May Hit Many Strains
• Bird flu vaccine may be more protective than thought; Swiss to stockpile | Markets | Headline News | Canadian Business Online
• Sanofi bird flu vaccine may offer wider protection

Technorati Tags: avian flu, bird flu, pandemic flu, Sanofi-Aventis, Sanofi

AVI BioPharma Initiates NEUGENE Antisense Clinical Program in Coronary Artery Bypass Grafting: Yahoo! Finance

The trial looks at improving outcome for bypass grafts in heart patients. The grafts will be immersed in a saline solution of the antisense compound AVI-5126 to see if that improves the outcome. The study will be double blind, randomized and placebo controlled so it sounds like they are doing everything right.

Here’s the pertinent paragraphs telling how this compound works.

AVI-5126 silences a gene known as c-myc, a key regulatory gene involved in cardiovascular restenosis. C-myc is believed to regulate the many downstream genes that produce the pathology of restenosis, namely cell migration and adhesion, collagen formation, secretion of extra-cellular matrix, and cell proliferation, among others.

Preclinical studies have shown that silencing c-myc just at the time of injury may be enough to prevent late-term consequences of intimal hyperplasia, considered the primary cause of vessel obstruction after CABG and intra-coronary artery stent placement.

Since this type of surgery is common in the US with 350,000 such surgeries taking place each year, this could be a major adjunct to the surgery to improve the overall outcome. What I think needs to be kept in mind though is that this is a phase !b/II study; after a safety evaluation of the first 110 patients it will then become a phase III trial and the patients will be followed for one year. I personally think that one year is a little too short. It could will end up that at the end of that time there is no statistically significant difference between the two groups. While I know folks involved are probably better informed than myself about this sort of follow-up, I can’t help but point out that many times folks are overly optimistic in such situations. I’d rather see them err on the side of caution and make the follow up longer; at least three years. He only downside to this approach is that investors see this is involving more time and money

Technorati Tags: AVI Biopharma, AVI-5126, antisense

Test to predict response to chemotherapy drug | Top News | Reuters.com

This is exciting news. Basically, people with lung cancer that express a gene called ERCC1 will likely not respond to cisplatin. For these patients, other chemotherapy should be considered. While not proven yet in large studies, this is interesting and might in the future allow oncologists to select the proper treatment based on genetic testing. Since chemotherapy can have devastating side effects, it is important to get a treatment that has the highest probability of success for a given patient. If you are one of those who would not respond to a given drug, regardless of how effective it is in the given population, you would want to know that before going through a treatment with nasty side effects that won’t work for you. The fact that 75% of people respond doesn’t do you any good if you are in the 25% group. I also think that until recently there seemed to be much more emphasis on finding genes that indicated a person would respond to treatment rather than identifying those who would not respond. I think both are important and in the case of oncology identifying those who would not respond is very important to avoid going through a treatment that causes serious side effects but with no really benefit.

Another example is the HER2 and Herceptin. Women with early breast cancer who have higher levels of HER2 are at significant increase risk of the disease recurring and worst prognosis. However, these very patients respond quite well to treatment with Herceptin. This test is routinely used now for women with breast cancer.

I see this as the future of personalized medicine and not the process of making a specific compound for an individual. Finding out who will and who will not respond to a given treatment will be of tremendous importance to medicine in the 21st century.

Other Sources

• HER2/neu - Wikipedia, the free encyclopedia
• NEJM — HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy
• Adjuvant Trastuzumab: A Milestone in the Treatment of HER-2-Positive Early Breast Cancer — Baselga et al. 11 (Supplement 1): 4 — The Oncologist
• Low ERCC1 Expression Correlates with Prolonged Survival after Cisplatin plus Gemcitabine
• Chemotherapy in Non-Small Cell Lung Cancer — Lord et al. 8 (7): 2286 — Clinical Cancer Research

Search Results

• her2 - Yahoo! Search Results
• her2 - Google Search
• ERCC1 - Google Search
• ERCC1 - Yahoo! Search Results

Technorati Tags: chemotherapy, cisplatin, genetic testing, Herceptin, personalized medicine, trastuzumab

New Sense of Caution at F.D.A. - New York Times

The article point to Avastin as an example where the FDA has asked for more data related to Genetech’s filing of the use of this drug in breast cancer. It is already approved for colon cancer. They also point to other drugs that have been approved in Europe but only have received an approvable letter here in the US. An approvable letter means the FDA would approve the drug if additional data is provided and the data supports the conclusions.

This is in contrast to the Institute of Medicine report that found the FDA is not doing its job adequately. So how can these both be true? I think a lot has to do with what material was looked at and how it was interrupted. I think both are correct. The FDA does need some changes and most importantly an increase in funding to adequately do its job. The recent food incidents of lettuce and spinach point to the lack of oversight in the food arena.

FDA Statement on Foodborne E. coli O157:H7 Outbreak in Spinach Update: Sunday, September 17, 2006
US FDA/CFSAN - Lettuce Safety Initiative

I do think though that the New York Times and Wall St. tend to focus more on the profitability and money side of things and ignore safety issues. I also think that some of the incidents of the drug industry not being more transparent has led to the overall reputation of both the industry and the FDA. As an example, Bayer recently failed to inform the FDA of data related to dangers with a heart surgery drug, Trasylol. It seems the company wanted to delay reporting these results until they could come up with other results to discount the negative study.

Bayer’s Duplicity on Drug Safety - New York Times

These sorts of incidents only play into the already widespread belief in the general public of the pharmaceutical industry being greedy and not having the best interest of patients at heart. This is an area where I truly believe reform is needed. Public disclosure of ALL studies and not selected studies should be required and there should be a centralized database for this that is accessible on the Internet.

So, both sides have valid point but here are the areas I think are in most need of reform.

1. Food Inspection: the FDA needs to be more proactive in the food area as evidenced by recent outbreaks of e. coli in spinach and lettuce.

2. Database to report publicly all studies preformed on a given drug. It should be required to be done in a timely fashion.

3. FDA needs the power to fine companies for violations. Currently there only have the power to pull a drug off the market. I’ve always thought it was strange and unreasonable that the FDA did not have this power. The EPA has this power and has been using it effectively for many years.

While I believe some reform is needed, I think it should be approached cautiously and without political ends in mind. If these areas are addressed, I think the FDA can bemuse a respected agency again in the near future.

Technorati Tags: FDA, FDA enforcement, food safety, Vioxx effect

FDA Issues Guidance to Industry for Development of Cell-Based Viral Vaccines

The New York Times also reported on this.

FDA Rules May Speed Flu - Shot Modernizing - New York Times

One of the important reasons for this is if the bird flu should happen to wipe out the chicken pollution, it would make producing vaccines using chicken eggs impossible and another method would need to be developed. It is good to see thought is going into this before something catastrophic happens.

Other Resources

• Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Starting Materials Used in the Production of Viral Vaccines for the Prevention and Treatment of Infectious Diseases
• FDA Rules May Speed Flu - Yahoo! Search Results
• FDA Rules May Speed Flu - Google Search

Technorati Tags: FDA, flu, vaccine

Merck Revises Regulatory Filing Timeline for MK-0524B, an Investigational Fixed-Dose Combination of MK-0524A and Simvastatin: Financial News - Yahoo!

Although the clinical trial schedule has NOT changed, the filing will not take place in 2007 as previously planned.

MK-0524B is an extended release version of niacin along with a flushing inhibitor. Niacin use to be used before the statins came on the market for controlling cholesterol. It works by not only lowering the LDL but also raising the HDL (good cholesterol). The main problem was the flushing the niacin causes and many patients quite taking niacin because of this side effect. I personally take niacin (over-the counter; OTC) in a non-flushing formulation since my total cholesterol is low but my HDL is very low so the ratio is not what it should be. I’ve been taking 500 mg twice daily for about a year now and am interested to see what the cholesterol levels are next time they are checked.

It is interesting that Merck is not comparing their new drug against a cheap OTC non-fluhing formulation of niacin. It is interesting that the drug would appear to be a triple combination; MK-0582A (an extended release version of niacin), a DP-1 selective antagonist (prevents flushing) and simvastatin.

Further Information

• Merck Revises Regulatory Filing Timeline for MK-0524B, an Investigational Fixed-Dose Combination of MK-0524A and Simvastatin
• Merck MK-0524B - Yahoo! Search Results
• Yahoo! News Search Results for Merck MK-0524B
• Merck MK-0524B - Google News

Technorati Tags: Merck, MK-0524B, niacin, simvastatin, Zocor

Glaxo’s Faustian Pill - Forbes.com

The increase in risk is described as 37% but in 62% of the patients with high blood sugars avoided developing diabetes. Without more data on the potential benefits, I don’t see this drug going anywhere. It may be useful in conjunction with a genetic test that might be developed to identify those who are at highest risks. If I was developing this drug, that’s definitely one area I would be actively investigating.

I think that the Vioxx factor may be playing a part. It seems everyone is looking for cardiovascular problems with just about any drug and if you look hard enough you find what you are looking for. now, I want to make it clear that I’m not saying we shouldn’t evaluate risks but that you have to weigh the risk against the reward. In this case, defining the rewards are much more difficult.

Technorati Tags: Avendia, GlaxoSmithKline, Vioxx factor

‘Pharm’ goats give birth to new drugs - Sunday Times - Times Online

The drug being produced is ATryn, an anti-clotting drug used to treat patients with hereditary antithrombin deficiency (HAD). This makes the patients vulnerable to deep-vein thrombosis. The drug is being developed by a US company called GTC Biotherapeutics.

There is also mentioned another company developing the drug Rhucin for treatment of angioedema (swelling of soft tissue). This is being developed by the Dutch company Pharming.

It is great to note that these life-savings drugs are being approved. I would note that this really only applies to biologics. I can’t see small molecules being produced in this way anytime in the near future.

Other resources

• Transgenic Animals
• Transgenic animal - Wikipedia, the free encyclopedia
• GlaxoSmithKline: The role of transgenic animals in biomedical research
• Public Perception of Transgenic Animals (pdf)
• Barnyard 101: An Introduction to Transgenic Farm Animals

Technorati Tags: ATryn, GTC Biotherapeutics, pharming, Rhucin, transgenic animals

BMS claims outsourcing no longer an option

While there is some truth to this, it also ignores what would happen if there is a down-turn in the industry or if a major problem should happen at a contract manufacturer. Although I hope it doesn’t happen, if such an event would occur, it would definitely have a major impact on the industry. Also, I think if major pharma companies have an excess of capacity, they won’t outsource but keep it in-house.

I firmly believe that outsourcing is indeed important but I don’t share the opinion that it is no longer optional. The choice to outsource should be made carefully and with a eye on what is important. not all activities can or should be outsourced. Outsourcing of activities that bring an added value to the company are ones that are prime candidates for outsourcing.

Technorati Tags: Bristol-Myers Squibb, drug development, outsourcing

Personally, I think this is a poor decision trying to compete on price. If price is truly the reason that process development and research is going to China or India, then offering only a 25% discount isn’t going to do it. They could go to India or China and save 50% over the low end of their offer.

I also firmly believe you get what you pay for. I’d much rather spend the extra $50,000 and get experienced people who have been in the industry for a while rather than a new industrial post-doc fresh out of graduate school.

I think this whole mentality in the US of focussing almost entirely on price is very detrimental. It serves to erode the expectations for price in the future. When you start offering low prices, this becomes the new norm and further price reductions are expected in the future. I’ll keep my eye on this to see what develops in the future.

Technorati Tags: Cambridge Major labs