QDIS Blog

Today seems to be genetic testing day on this blog. Reuters had a report recently on a new genetic test that will likely find great use in oncology.

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

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A recent article in the New York Times reports that the FDA may be more cautious in the after-math of Vioxx. I call this the Vioxx Effect.

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

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In what I consider to be a very good development the FDA has now issued guidance to industry on developing cell-based viral vaccines. Right now, chicken egss are used and the process hasn’t changed in many years. Development of cell-based methods for manufacturing vaccines could increase the ability to produce vaccines.

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

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Merck has said that they will not file an NDA for MK-0524B. It is being co-administered with simvastatin (Zocor ®).

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

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I found this recent Forbes article interesting. It reports on a large study called DREAM of the diabetic drug Avendia and how some see it as indicating an increase in heart attacks and strokes.

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

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I reported on pharming before but wanted to point out this latest article from the Times of London.

‘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

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I came across this article and think there may be a point to it. The authors claim that outsourcing in the pharmaceutical industry is no longer an option but a necessity.

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

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I read in a recent Chemical and Engineering news issue that Cambridge Major Labs will be launching a cut-rate research service. They are evidently trying to compete head-to-head with cheaper labor sources in China and India. To do this, they will hire industrial post-docs to do the work. The typical rate for an FTE in the US is $200,000 vs $60,000 annually in India or China. Cambridge Majors will be offering their industrial post-docs to their customers for a rate of $120-150,000.

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

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The FDA has given the okay to Iomai to test their flu vaccine in a patch based delivery system. They will compare it against the standard flu shot.

United Press International - Health Business - FDA OK’s trial of Iomai’s flu vaccine patch:

I find this an interesting delivery system for vaccines and this could be a major step forward. THeir are some people I know who don’t get the flu shot each year mainly because they have a fear of needles. I do know though that getting any sort of medicine across the skin barrier is difficult and one of the primary reason there aren’t more drugs delivered by patches.

Technorati Tags: flu, Iomai, vaccine

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Adeza has a new drug to help prevent premature births and is seen is a promising drug as reported by Forbes.

Adeza Shares Seen As Attractive Following FDA News - Forbes.com:

The article covers that the Reproductive Health Drugs Advisory Committee has recommended for approval Gestiva indicated to prevent premature births. Premature births occur much more frequently now than in past years mainly due to advancements made in fertility treatments; currently about 12% of all births are premature (less than 37 weeks gestation). Also, premature births tend to be very costly to the health care system. According to this site March of Dimes put the cost in 2003 of $11 billion for preterm birth.

Further Resources

• Press Release from Adeza on FDA recommendation for approval
• Adezas Gestiva recommended for FDA approval - Pharmaceutical Business Review

• FDA questions effectiveness of Gestiva at preventing preterm labor

Technorati Tags: Gestiva, premature birth, Adeza

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