DALLAS, Texas—Despite a late-stage regulatory hiccup, pharmaceutical executives and patient advocates at a neuromuscular disease meeting here predict the US Food and Drug Administration (FDA) will still approve the first-ever gene therapy for Duchenne muscular dystrophy (DMD) as expected on May 29, 2023.

SRP-9001 (delandistrogene moxeparvovec), developed by Sarepta Therapeutics, was easily the chief topic of conversation at the Muscular Dystrophy Association’s 2023 Clinical & Scientific Conference, held March 19-22, 2023.

Donald S. Wood, PhD, the MDA’s president and CEO, said he isn’t sure why the federal agency recently announced it would convene a meeting of independent experts to review Sarepta’s application.

Continue Reading

“They’re seeing something in the data that has raised questions. I don’t know about what, but I’m sure it’s not a safety issue,” Dr. Wood told Rare Disease Advisor, adding that it’s most likely a question of efficacy. “If it were safety, they would have never even considered originally releasing it in May.”

Dr. Wood said he hopes the FDA will approve the therapy this year. At any rate, the delay “gives us more time to get prepared,” he said.

MDA officials
Muscular Dystrophy Association (MDA) officials Paul Melmeyer, vice president of public policy and advocacy; Sharon Hesterlee, chief research officer; and Barry J. Byrne, MD, PhD, chief medical advisor, at the MDA’s 2023 Clinical & Scientific Conference in Dallas, Texas. (Photo by Larry Luxner)

“The newly diagnosed patient is in a terrible situation. They hear about a gene therapy, and the family is going to want to jump into it immediately. They’ll be very upset when they learn that the soonest appointment could be a year from now.”

Sharon Hesterlee, PhD, the organization’s chief research officer, said it’s difficult to speculate on what might happen.

“If the FDA had no questions at all [about the drug]—if they either loved or hated it—we would not be having an advisory committee. But this doesn’t mean it won’t be approved,” she said. “Until we hear how that [advisory committee meeting] goes, we won’t know. But they’ve said this is not going to delay the decision.”

Paul Melmeyer, the MDA’s vice president of public policy and advocacy, said he’s still “excited and eager” to see the drug approved within the next few months as originally envisioned.

“We never believe that convening outside experts to really ensure that the therapy is safe and effective is a problem,” Melmeyer said. “In doing so, there’s also an opportunity for the community to participate and make their views known.”

Dallas-based pediatric neurologist Diana Castro, MD, said she doubts the new therapy will retail for less than $4 million—nearly double the $2.1 million price tag of onasemnogene abeparvovec-xioi (Zolgensma®), marketed by Novartis for spinal muscular atrophy (SMA).. Yet cost isn’t the only obstacle, said Dr. Castro, who inaugurated her own Neurology and Neuromuscular Care Center in suburban Denton during the MDA conference.

“About 14% of Duchenne patients will likely be positive for antibodies and therefore not eligible for the Sarepta gene therapy,” she said. “If they approve it for 4- to 7-year-olds, many of the boys I treat will have a chance. And even if they do, insurance will not allow us to start administering it until the end of this year.”

Barry J. Byrne, MD, PhD, directs the Powell Gene Therapy Center at the University of Florida in Gainesville. He’s done extensive research on several neuromuscular diseases, including DMD.

Dr. Byrne, who’s also the MDA’s chief medical advisor, predicts SRP-9001 will cost at least $3.5 million. That coupled with the larger potential patient population could mean a dramatically higher total cost to the healthcare system. 

“You have to consider the total cost to the ecosystem of providers. There are 10 times as many Duchenne patients as SMA patients,” Dr. Byrne said. “In 2.5 years, some 2500 doses of Zolgensma have been administered worldwide, probably 1800 in the U.S. alone. But the incident population of Duchenne patients eligible in the U.S. is between 2000 and 4000 children. From day 1, they’ll be seeking to receive treatment.”