Drug Truths

A site devoted to teaching about drug discovery and development.

The FDA Is Justified in Asking For Outcome Studies

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On August 10th, the Wall Street Journal published a letter to the editor entitled, “The FDA Isn’t as Innovative as It Likes To Think It Is,” in which Skyline Ventures Founder, Dr. John Freund, lashed out at the FDA.  Specifically, he challenged the view espoused in Margaret Hamburg’s WSJ Op-Ed piece: “America’s Innovative Agency: The FDA.”  The FDA’s self-anointed role incenses Freund, who wrote:

“The FDA has tightened up the requirements for approving new drugs for adult-onset diabetes, a disease that affects approximately 25 million Americans.  The result is that performing the clinical trials for a new diabetes drug is so long and costly that no venture capital firm will finance a new diabetes drug.”

He also has doubts about the FDA’s desire to approve new drugs to treat obesity, writing, “In the past year, the FDA rejected three separate drugs to treat obesity, including one for which the FDA’s own advisory panel recommended approval.  As a result, no venture capital firm will now finance a new effort to develop a drug for the obesity epidemic.”

Despite the fact that I am a “Big Pharma” veteran, I am on the side of the FDA on this one.

First of all, the relatively conservative position taken by the FDA in obesity and diabetes is not unique to these therapeutic areas.  In fact, it is seen in new drugs for cancer, osteoporosis and heart disease.  No longer will the FDA approve a drug for obesity based solely on its ability to induce weight loss.  Similarly, the FDA wants to see more than blood sugar lowering before approving a drug for diabetes.  While both are meaningful markers for improving the respective disease condition, the FDA also wants to see outcome studies, that is, two to three year long studies showing that the weight loss or lowering of blood sugar actually correlates to a reduction in heart attacks and strokes, the unfortunate end results for diabetes/obesity.

Why is the FDA asking for long-term data?  Won’t weight loss and/or blood sugar lowering automatically result in enhanced survival?  Surprisingly, the answer is no.  A recent case-in-point was the widely prescribed anti-diabetic agent, Avandia.  This drug was approved on the basis of its impressive blood sugar lowering ability.  However, and to the surprise of many, this drug DID NOT reduce adverse cardiovascular events in long-term studies conducted after it was approved for sale.  In other words, lowering blood sugar had no impact on the ultimate desired outcome.

In the case for weight loss agents, the FDA’s rationale is likely different.  A true weight-loss drug is going to be widely prescribed and theoretically could become one of the biggest drugs in history.  With the likelihood of such broad usage, long-term safety of such a drug needs to be shown before unleashing it on the public.  This position is best supported by the diet drug phen-fen, which causes modest weight loss, but which is associated with severe cardiac damage on prolonged use.

The same is true for new drugs in other classes.  Studies have shown that just because a drug shrinks the size of a tumor doesn’t mean it enhances survival.  Or, if a compound stabilizes bone formation, it may not prevent fractures.  And there are a number of studies that show that raising HDL, the good cholesterol, doesn’t reduce heart attacks.  Faced with this situation, the FDA has done the logical thing – it wants outcome studies to justify approval for drugs that will need to be used by patients for decades.

The assertion that Dr. Freund makes that “no venture capital firm will now finance a new effort to develop a drug” for diabetes and obesity is not true.  Catabasis, a biotech company in Cambridge, MA, recently raised almost $30 million from VCs to support their exciting new approach to diabetes.  And Gelesis, a company that has been formed by PureTech Ventures (where I am a Senior Partner), is focused on obesity and has also recently raised funds to support its R&D program.  Despite this admittedly tough regulatory environment, good ideas are still garnering investments.

There is a positive aspect to all of this.  If a compound can successfully clear these hurdles, it will be a blockbuster.  The manufacturer will be able to say that its new compound not only causes weight loss, but it also reduces heart attacks and strokes.  The same would be true for a diabetes drug that reduces cardiovascular events as well.  Without question, the FDA’s regulations benefit everyone involved.


Written by johnlamattina

August 11, 2011 at 8:53 pm

Posted in Uncategorized

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2 Responses

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  1. The need to shift from treating disease symptoms (like high blood glucose levels) to therapies and interventions having a positive fundamental impact of the disease itself was embraced at BIO 2011 in June and is clearly a central concept already known and embraced by the FDA. John, your blog post helps to elevate awareness of how our changing understanding of science is also changing the regulatory framework for future innovations. I am not sure why learning from the past experiences with many drugs and drug categories is not embraced as progress by some like Dr. Freund. Fostering a healthy and productive discussion will help the many stakeholders involved in health and disease (from patients (current and future) through to payers and policy makers and many others) to participate productively in supporting future innovations.

    Lynn Hanessian

    August 14, 2011 at 7:00 pm

  2. The FDA needs a major overhaul! Enough said.


    August 29, 2011 at 3:01 am

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