FDA Considers New Muscular Dystrophy Treatment Using Experimental Gene Therapy: Shots

Susan and Chris Finazzo enrolled their sons Dylan and Chase in a gene therapy study for Duchenne muscular dystrophy. The experimental treatment is still being studied, but researchers hope it can help prevent the devastating effects of the disease.

Natalia de la Rosa Reyes/Susan Finazzo

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Natalia de la Rosa Reyes/Susan Finazzo

Susan and Chris Finazzo enrolled their sons Dylan and Chase in a gene therapy study for Duchenne muscular dystrophy. The experimental treatment is still being studied, but researchers hope it can help prevent the devastating effects of the disease.

Natalia de la Rosa Reyes/Susan Finazzo

When Chase Finazzo was only a few years old, his parents noticed that Chase was quite clumsy. But they didn’t think it was anything serious.

“He was falling a lot. Not a lot. But he had trouble climbing on the playground equipment. He fell down the stairs several times at his kindergarten,” says his mother, Susan Finazzo, 40, who lives at Miami. .

Chase’s younger brother, Dylan, was more agile. But he started walking a little late.

“We don’t think about it. He just has weak ankles. He has tiny little braces for toddlers,” she says. “He’s seeing an orthopedic surgeon. We have PT. We’re everywhere.”

So Susan and her husband Chris Finazzo were stunned when doctors told them both boys had Duchenne muscular dystrophy. Although rare, the disease is the most common inherited neuromuscular disease in children. It affects approximately 10,000 to 12,000 children in the United States

The disease, which almost exclusively affects boys, destroys muscles. Most boys end up in wheelchairs before they become teenagers. Eventually, their heart and lungs fail. Most people with the disease die in their 30s or 40s. It is incurable.

“It’s absolutely devastating,” says Susan Finazzo. “You end up going through a grieving process. You mourn the loss of the life your child should have had.”

Finazzo couldn’t help but wonder about his kids, “Are they going to be able to go to college? Will they live that long? Will they be able to fall in love? Have children of their own? you were going to have soccer practice. And now you’re wondering, how long am I going to spend with them?”

Finazzo and her husband started giving their sons steroids to help them, even though the drugs can cause side effects and cannot slow the disease. They also started looking for better options.

Finally, they nominated Chase, now 8, and Dylan, now 5, for a study testing experimental gene therapy for Duchenne muscular dystrophy.

Gene therapy works by infusing billions of harmless viruses that have been genetically engineered to carry a gene to patients’ muscles. The gene produces a miniature version of a protein called dystrophin, which boys with muscular dystrophy lack or don’t have enough of. The hope is that this “micro-dystrophin” will at least help slow the progression of the disease.

“Hopefully it can extend their life a bit. At the end of the day, as a Duchenne parent, you don’t even care about the wheelchair anymore. You don’t care about not walking,” says Finazzo. “I just want them to live longer. I want them to live long enough to enjoy what life is. So if that moves the needle in their lifespan – even if it does for a day – it’s worth it.”

But there is an intense debate about it. Sarepta Therapeuticthe Cambridge, Mass. company that developed the treatment wants the Food and Drug Administration to approve the gene therapy largely based on how much micro-dystrophin it produces in patients’ muscles — with no evidence direct that really helps relieve symptoms and prevent disease progression.

The FDA has convened a committee of independent advisers to consider whether to recommend approval on May 12.

Approval would go through a process known as accelerated approvals. This allows the FDA to quickly approve promising treatments before strong evidence is available that the therapy helps, as long as the companies promise to conduct follow-up studies afterwards to prove it works.

“We are dealing with a very serious rare disease. A deadly disease. Every day matters to these patients,” says Douglas Ingram, CEO of Sarepta. “This could be the most important therapy developed to date for children with Duchenne muscular dystrophy. We have, at least from our perspective, the perfect opportunity to use the fast-track pathway.”

But this accelerated approval process is controversial because some companies are failing to deliver on their promises to confirm that their treatments work. A drug approved in this way to prevent premature births has been recently removed after being found useless.

Sarepta’s gene therapy for muscular dystrophy would be the first gene therapy approved under the accelerated approval process. And the request has would have sparked an intense debate within the FDA.

Sarepta has not yet completed the follow-up studies required for three other dystrophin-based treatments for muscular dystrophy previously approved under the fast-track approval process, according to Dr. Reshma Ramachandran, who studies drug approvals at the Yale School of Medicine.

That leaves open the question of whether micro-dystrophin levels are an accurate way to assess treatments for the disease, she says.

“We still don’t know whether or not these very expensive treatments provide significant clinical benefit, or if we’re just guessing,” Ramachandran said.

“This question has been around since 2016: Is dystrophin an appropriate proxy measure of clinical benefit for Duchenne muscular dystrophy. It’s still a looming question. And the fact that it’s, you know, seven years older late and we still don’t have an answer is a bit appalling,” she said.

If that doesn’t help, Ramachandran fears the approval could discourage the development of other treatments that might work and prevent patients from being eligible for those therapies.

And then there is the matter of cost. Although the company has yet to release projected costs, other recently approved gene therapies have cost up to $3 million to treat each patient.

The costs, which aren’t always covered by insurance, could drain money that families could otherwise use for much-needed treatments, such as physiotherapy and home care, she says.

“It’s really bad,” she said.

dr. Glen Nuckols at the National Institute of Neurological Disorders and Stroke said it could not comment directly on Sarepta’s request. But he too expressed reservations about using a surrogate marker.

“There’s certainly data to suggest that you start making dystrophin, that will lead to tissue regeneration and increased strength. But I think the relationship between the exact level needed, we would probably like to have more data at that topic.” Nuckolls said.

But Ingram, CEO of Sarepta, said waiting for more data would come at a cost.

“During this waiting period, some six to 800 children will die. Some 600 to 800 children will be confined to electric wheelchairs for the rest of their lives. Six hundred to 800 children will be confined to permanent ventilation,” Ingram said. . “All of these children… will be damaged beyond repair in ways that we cannot reverse.”

The company says it has preliminary data indicating that gene therapy is helping patients, and already has a large study to confirm which ones are on the way.

The company’s request is backed by groups like the Association of muscular dystrophy.

“Surrogate endpoints such as dystrophin measurements allow for better access,” says Dr. Barry Byrne of the University of Florida, the association’s chief medical adviser. “An analogy would be that a drug that lowers cholesterol should have an improvement in cardiovascular mortality. So it’s a similar analysis.”

“We think it slows down the disease and hopefully stabilizes these patients,” says Debra Miller, who leads Cure Duchenne, a patient advocacy group that helped fund Sarepta. “We have high hopes that at least for many years we will be able to stop the downward progression of this disease through gene therapy.”

For her part, Susan Finazzo knows the drug may not help her sons, but she is hopeful.

“I’m so excited that we even had the opportunity to participate in this [study]. Because the majority of children cannot. So it’s an incredible opportunity,” she said.

Every year, on her sons’ birthdays, she remembers how little time they have to help them.

“Birthdays are especially difficult because they’re bittersweet,” says Finazzo. You’re so happy but you also know it’s a year less with them. It’s just a reminder of the ticking clock.”

The digital version of this story was edited by Carmel Wroth; program edited by Scott Hensley.