The Race to Yes: A Chance to Improve the Process

Next Thursday, an FDA advisory committee will meet to consider whether to approve a treatment for Duchenne muscular dystrophy. The last time an FDA advisory committee met to review a therapy for this fatal childhood disease, things did not go smoothly. — Portrayed in the media as a heated showdown between the FDA and desperate families, the “ad comm” meeting for Exondys 51 came at the end of a long, drawn-out process that took way too long and involved way too many missteps. For the sake of 200,000 children around the world with Duchenne — and 30 million Americans who suffer from rare diseases – we’ve got to do better.

Our process for evaluating rare disease treatments needs to evolve to keep up with incredible advancements in genetic medicine. And it needs to be improved to better reflect the urgency of people whose lives are severely compromised and shortened by life-threatening diseases. Figuring out how to do this will take collaboration, reform, and leadership. But we have an immediate, tangible opportunity at hand to improve a particular part of the process –- the advisory committee meeting. Here are three meaningful, specific ways to do so.

For background, the FDA convenes an advisory committee meeting to get informed external input on a drug’s application for approval. But certain things must happen to ensure that the “ad comm” is a genuine exchange of information, an earnest effort to enhance understanding of whether a drug is safe and effective.

First, it is critical that physicians who have treated the target population and scientists who have studied the disease in question be included as advisory committee members. This may seem obvious, but it did not happen the last time around. The panel that voted on Exondys 51 had minimal experience with neuromuscular disease. Of the nine “experts” who voted on whether to approve the first-ever treatment for Duchenne muscular dystrophy, only two had ever treated a patient with the disease. There are 7,000 rare diseases –FDA employees can’t possibly be expected to know the minute details of every body of research. But we can – and must – ensure that those who do know the details are included as voting committee members.

Second, this committee should be encouraged to engage in a meaningful dialogue with additional outside experts who can further elucidate data, provide context, and clarify fine points. Last April, thirteen Duchenne muscular dystrophy experts traveled from around the world to participate in the open public hearing section of the Exondys 51 meeting. Each was given exactly three minutes to speak, at the end of which their microphones were shut off. When an ad comm member asked a highly technical question of an expert who had traveled from the University of Washington, the chairman did not allow time for an answer. When another DMD expert tried to address the FDA’s misinterpretation of his own data, he too was shut down.

Third, the questions posed to the panel should be clear and succinct. For Exondys 51, the questions presented by the Division of Neurology were convoluted and confusing, prompting one panel member to vote against approval despite his conclusion that “the drug definitely works, but the question was framed differently.” Another panel member abstained “ because I’m uncomfortable by the language of the question because I think it’s a bit leading.” Questions should be streamlined, designed to elicit the answer to the one question that’s on all of our minds: Based on the information we have in hand, should doctors be permitted to prescribe this medication?

The ad comm comes near the end of a long and winding drug development process that takes years, sometimes decades. Science is advancing and evolving quickly, and the drug evaluation process must evolve as well. Many years pass from the day a drug company starts working with regulators until the day the FDA decides whether doctors can prescribe the medicine. In this era of genetic breakthroughs and personalized medicine, we must ensure that the regulatory process is not the rate limiting step in getting potentially life-saving treatments to people who suffer from debilitating diseases that rob them of quality of life and drastically shorten their lives. That’s a tall order, but thankfully, the new FDA Commissioner has embraced it. “Unless we find ways to modernize how we approach our work, and make more efficient use of our resources, then we’re going to get fewer medicines, and higher costs,” he explained in a recent speech. “We’re not going to realize the benefits of the scientific advances we’re seeing as quickly, if we see them at all.”

As plans are put in motion to improve the drug development process, there are concrete steps we can take right now. Next week’s advisory committee meeting should be a scientifically robust, meaningful exercise that truly helps determine whether this new drug is worthy of approval.

Marissa Penrod & Tracy Seckler
Co-Founders, the Race to Yes