Sarepta and the Regulation of Hope

FDA’s approval of Sarepta’s Exondys 51 (for Duchenne muscular dystrophy) is controversial and important. More importantly, it is a teachable moment for 21st-century regulatory science.

It certainly shows there is robust debate inside the FDA concerning “benefit/risk.” Unfortunately, media coverage to-date has consistently buried the headline. Post-approval comments and commentary have been largely pernicious gossip and petty score settling. We must transcend such lowest common denominator conversation not just because it’s tawdry — but because it misses the point.

Yes, Serapta’s clinical program was amateurish and their trial design naïve. But there was undeniable evidence of … hope.

Is “hope” now considered a validated biomarker? Certainly not — but it’s more complicated than that. The FDA’s Patient-Focused Drug Development program has begun to shift the agency/advocate relationship from anecdote to ally. How much risk is a patient willing to accept? How can that tolerance be measured in order to factor it into a regulatory benefit/risk calculation? What weight should patient input have relative to a randomized controlled trial? Can that calculation to reproducible across therapeutic categories?

Barely discussed in this debate are the robust and real-time post-marketing requirements for Exondys 51. The FDA will be looking in real time at real word evidence generated from real patients. And while the FDA cannot put anecdotes on the drug label, real world evidence is undeniably the new star on the precision medicine horizon. The tool set for using this treasure trove of healthcare information is nascent and the tasks as are daunting as the opportunities But it’s a valuable new opportunity to drive a more patient-centered FDA and should act as a reminder that the agency’s 21st century mission is to embrace a more complete life-cycle approach to the healthcare technologies it regulates. Patient passion is important to share. When combined with data and a more dispassionate understanding of regulatory paradigms, a patient-driven pathway can and must evolve into a tool used to impact regulatory decision-making.

Policies and regulations that seek to limit risk are often shaped by the immediate fear of sensational events. This perspective is commonly called “The Precautionary Principle” which in various forms asserts that unless innovators can demonstrate that a new technology is risk free, it should be not allowed into the marketplace.  Moreover, any product that could possibly be dangerous at any level should be strictly and severely regulated.  In reality, this punished patients and stymies innovation. There is never a medicine that is 100 percent safe.

Joshua Lederberg, the Nobel Prize Laureate once observed that the failure of regulatory, legal and political institutions to integrate scientific advances into risk selection and assessment was the most important barrier to improved public health.   

According to Lederberg, “the precedents affecting the long-term rationale of social policy will be set, not on the basis of well-debated principles, but on the accidents of the first advertised examples.”

Exondys 51 does not mean a free pass for bad science. Not ever. What is does mean is that the FDA (and from the highest levels) is rightly embracing regulatory dimensionality, a combination of a scrupulous review process and pragmatism. Together with a recalibrated sense of regulatory velocity (Speed + Accuracy + Public Health Need), it’s the agency’s next step toward 21st-century regulation — toward entrepreneurial regulation. The FDA as innovation accelerator.

So, drug developers, beware! The FDA is going to apply a rigorous assessment of protocol, process, and data (both pre-and post) as always. The agency’s going to call it as they see it, unbowed by any outside pressure. Beware — and applaud the first awkward step — it’s a long way to the finish line.


Peter J. Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest

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