Marks: FDA open to using single-arm studies for accelerated approval of rare disease gene therapies

Marks, who is the director of the FDA’s Center for Biologics Evaluation and Research, said Monday during a webinar organized by the NYU Grossman School of Medicine that the FDA is “trying to be patient-focused.” Under Marks, the FDA has appeared more flexible with accelerated approvals and the kinds of trials and results needed to bring rare disease therapies to market.

“We’ll use our accelerated approval provisions to lean in and try to get things across the finish line,” he said.

He discussed the use of single-arm studies for potential accelerated approvals, noting that randomized controlled trials, which are considered the gold standard study in drug development, may not always be feasible for very rare diseases that only affect a few hundred patients in the US.

But even in cases where there are enough patients, a randomized controlled trial may not always be needed. He pointed to Zolgensma, a gene therapy marketed by Novartis for spinal muscular atrophy, that the FDA fully approved based on single-arm studies that showed striking results compared to the natural history of the debilitating muscle disease.

“Some of this flexibility is increasingly being shown,” Suyash Prasad said about the FDA’s approach to biomarker data. Prasad previously was chief medical officer for Audentes — which was acquired by Astellas — and Taysha Gene Therapies, and now consults for gene therapy companies.

He pointed to the case of Grace Science, a biotech company co-founded by Nobel laureate Carolyn Bertozzi that’s developing a gene therapy for a very rare disease known as NGLY1 deficiency. Earlier this month, Grace Science received FDA clearance to begin a single-arm Phase I/II/III study that features both clinical and biomarker endpoints.

Marks said that gene therapies are particularly “well-tailored” to accelerated approval because they often are attempting to replace or knock down a protein, which can be measured and used as a biomarker. Protein expression levels in the blood can be measured fairly easily and can be used as surrogate endpoints in the accelerated approval process.

He also reiterated his concerns around reimbursement for gene therapies, which are among the most expensive treatments in the US. “For us, it’s very important that we have enough evidence initially through a biomarker that we can get an insurance company to reimburse for these products, because this is a major issue, right?” he said. “If these products can’t get paid for, they’re not going to get to patients, and we’ve seen that time and time again.”

Marks also noted that the agency hopes to work more closely with patient advocates. However, some patient groups have close financial ties to drug developers.

“What we probably will try to work toward is more of this incorporation of listening to patient advocates, potentially having meetings or workshops where we have both patient advocates and industry involvement, and also just having our reviewers try to have more of a sense of what patients are living with or their families are living with,” he said.

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