John LaMattina: FDA tries to disavow role in higher hurdles for new drugs
pharmafile | July 2, 2012 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | FDA, John LaMattina, Pfizer, US, discovery, drug
As evidenced by various blog posts that I have written over the past year (e.g., “Why Doesn’t the FDA Get more Respect?”), I appreciate both the important role that the FDA has in bringing new medicines to patients as well as the challenges it faces both politically and scientifically.
Furthermore, I think they have excellent leaders such as Dr Janet Woodcock, the FDA’s director of the Center for Drug Evaluation and Research (CDER). Yet, even to a supporter like myself, the organisation can at times make baffling presentations.
A recent talk given by Dr Woodcock, entitled “Today’s Biomedical Innovation: Lost in Translation,” is such an example. I was not in attendance at this presentation at the QB3 Entrepreneurs’ Discussion at the University of California, San Francisco. But I have read both the slides that Dr Woodcock showed and the subsequent commentary about it, and I come away feeling pretty disheartened.
To be fair, Dr Woodcock made a lot of good points in her talk. She appropriately raises a major issue facing the biopharmaceutical industry in that it “currently takes more than 10 years and requires an investment of over $1 billion to bring a single innovative drug to market”, and that these “costs are driven by increased expectations… about evaluating the performance of the drug (both safety and efficacy) before it goes on the market”.
In posing various solutions to this problem, Dr Woodcock recommends a greater role of Academia in drug development “leading to new evaluative tools for predicting, understanding and assessing the effects of medical products in the relevant species (people)”.
Actually, this is already happening with many of the major pharma companies establishing these very collaborations with investments on the order of hundreds of millions of dollars at major clinical research centres around the world. It is obviously pretty hard to argue with Dr Woodcock on that point.
But Dr Woodcock begins to stray into areas where I think she is off base. For one thing, she asserts that “many late-stage [clinical] failures are due to efficacy problems”. That’s not exactly true. It is only when companies take compounds into late-stage development with little or poor proof-of-concept data where this happens.
The majority of Phase III clinical trial failures are due to unforeseen, unpredicted side-effects or else due to finding that, in direct comparison to existing therapy, the new drug doesn’t show the superiority necessary to be successful commercially. Dr Woodcock goes on to advocate for the generation of ‘evaluative tools,’ new methodologies that can better predict the performance of a compound in late-stage studies.
This is a terrific idea. In fact, companies are expending a huge amount of resources both internally and externally to do just that. For example, great technology already exists for measuring the impact of new drugs on reducing atherosclerosis on the artery.
If a company has a new drug that it thinks will reduce atherosclerosis by shrinking arterial plaque, thereby widening the artery size, theoretically this compound will reduce the risk of heart attacks or stroke. But here’s the rub. The FDA will never approve such a drug based on having this biological effect alone.
Along with this observation, the FDA will require for approval that the drug’s sponsor carry out 3-5 years of studies showing that the reduction of plaque coincides with fewer heart attacks and strokes.
Now, I don’t necessarily think that the FDA is wrong in making such demands. After all, there are a number of examples in recent years where, although a drug had what appeared to be a beneficial effect (such as the lowering of blood glucose with the diabetes treatment, Avandia), long-term studies showed that the compound didn’t have the desired long-term health benefit but rather increased mortality.
Thus, new drugs to treat chronic diseases, such as obesity, diabetes, or heart disease, are now required to undergo long-term outcome studies before being approved. It certainly behoves biopharmaceutical companies to learn as much as they can about a drug’s risk-benefit potential before starting expensive Phase III trials. But, there is simply no way that the FDA will approve a drug based on improving biological parameters without long-term studies.
Here is an interesting test case to watch. I recently wrote about exciting science that has led to a novel mechanism to lower LDL (‘bad’) cholesterol. This approach involves blocking the actions of PCSK-9 and inhibitors of this protein that are more potent than statins in lowering LDL cholesterol.
The importance of lowering LDL in reducing heart attacks and strokes in patients at risk is beyond a doubt. Will the FDA approve these new drugs based on LDL lowering alone? I strongly doubt it.
My guess is that the FDA will require a long-term risk-benefit study to be certain that this new mechanism doesn’t also carry with it unforeseen toxicology before such a drug is prescribed to thousands of patients. I don’t have an issue with the FDA requiring such studies. I do have a problem, however, with the implication that the biopharmaceutical industry has to be smarter to succeed.
A lot of what Dr Woodcock is advocating for is already happening. Unfortunately, these advances in science won’t change FDA requirements for approval.
John LaMattina is the former head of R&D at Pfizer. His latest blog posting can be read on the Forbes site.
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