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Sarepta’s application to obtain accelerated approval for Eteplirsen for Duchenne Muscular Dystrophy (DMD) was rejected by an FDA advisory committee on Monday. Although the committee was told it had some flexibility, it could not overcome the FDA’s rules to vote in favor of patients' interests.
No one wants to deny sick children a drug that might help them. Yet, that is exactly what happened on Monday in spite of the efforts of the experts on the panel who clearly struggled between the flexibility they were told they had, and the written questions on which they were required to vote.
Here is the wording of the key question regarding accelerated approval.
Question 2: Has the Applicant [Sarepta] provided substantial evidence from adequate and well-controlled studies that Eteplirsen induces production of dystrophin to a level that is reasonably likely to predict clinical benefit?
The vote was 6 yes, to 7 no, with zero abstentions.
The panelists who voted no gave three broad reasons for their vote.
- They felt the clinical trial was not well-controlled. The trial involved only 12 patients, and there was no placebo group for comparison.
- They questioned whether Eteplirsen induces production of dystrophin. The methods used to measure dystrophin were not precise enough to be confident that the small 0.9% increase in dystrophin levels was not due to measurement errors.
- They could not say whether a 0.9% rise in dystrophin levels was enough of an increase to “be reasonably likely to predict clinical benefit.”
The heart of the matter is that Eteplirsen did not raise dystrophin levels by a large amount. If dystrophin levels had been increased by a bigger margin everyone would have been more comfortable about the trial design, the measurement issues, and whether it would have been likely to have a clinical benefit.
Is a 0.9% increase in dystrophin levels likely to have a clinical benefit? If you are not even sure that the increase is real, you have to answer no.
The most powerful argument for voting yes was the presence of all 12 boys who took part in the clinical trials, 10 of whom were still walking 4 years after beginning treatment with Eteplirsen. It is clear that all 12 boys, even the 2 who could no longer walk, were doing much better than anyone expected based on the normal progression of the disease.
When you consider the fact that in all the years of clinical trials, Eteplirsen has proven to have an excellent safety profile, it is hard to accept that rejecting this drug is the right decision.
Why would anyone want to deny DMD patients the use of a drug that everyone agrees is safe? Yet, the FDA might now stand in the way of patients who want to use this drug because it has not yet been proven effective.
For this reason, the idea that the FDA should only approve drugs that are safe and effective deserves re-examination.
Perhaps the FDA should grant two kinds of approvals, one for safety and another for efficacy.
Imagine if the advisory committee had been asked to vote on whether Eteplirsen is safe to administer to DMD patients at the dosages used in the trial.
I think this would have easily passed by a large majority. If the FDA were empowered to approve a drug that was deemed safe but not yet proven effective, then the decision about whether to use the drug would be placed where it should be, with patients and their doctors.
Physicians swear an oath that includes among other things a promise to do no harm.
It is time to recognize that it just as harmful to the public for the FDA to prevent an effective drug from being approved as it is to approve an ineffective drug.
Consequently, allowing doctors to use drugs that are proven safe but not yet proven effective is more consistent with the physicians’ oath.
This vote against approval for a safe drug is a setback not just for DMD patients, but also for anyone who now has or who might ever have a medical condition for which there is not yet an approved treatment.
The FDA advisory committee came to the only conclusion that the current rules for drug approvals would allow. It’s time to change the rules.
Disclosure: I am the portfolio manager for a mutual fund advised by Marketocracy Capital Management, an SEC registered investment advisor. Before relying on the opinions expressed in this article, you should assume that Marketocracy, its affiliates, clients, and I have material financial interests in these stocks and may hold or trade them contrary to these opinions when, in our view, market conditions change.
