Gene therapy for muscular dystrophy stirs hopes and controversy

When Chase Finazzo was just a few years old, his parents noticed Chase was pretty clumsy. But they didn't think it was anything serious.

"He would fall a lot. Not like a lot a lot. But he had trouble climbing playground equipment. He fell down the stairs at his pre school a couple of times," says his mother, Susan Finazzo, 40, who lives in Miami.

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

"We're not thinking anything of it. He's just got some weak ankles. He's got some little tiny little orthotics for toddlers," she says. "He's sees an orthopedic surgeon. We've got PT. We're all over it."

So Susan and her husband Chris Finazzo were stunned when doctors told them both boys had Duchenne muscular dystrophy. While rare, the disease is the most common inherited neuromuscular disorder among children. It affects an estimated 10,000 to 12,000 children in the U.S.

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

"It's absolutely devastating," says Susan Finazzo. "You end up going through a mourning process. You're mourning the loss of the life that your child should have had."

Finazzo couldn't help but wonder of her children: "Are they going to be able to go to college? Are they going to live that long? Are they going to be able to fall in love? Have children of their own? You thought you were going to have soccer practices. And now you're wondering: How much time am I going to have with them?"

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

Finally, they volunteered Chase, who's now 8, and Dylan, who's now 5, for a study testing an experimental gene therapy for Duchenne muscular dystrophy.

The gene therapy works by infusing trillions of harmless viruses that has been genetically modified to ferry a gene to patients' muscles. The gene produces a miniature version of a protein called dystrophin, that boys with muscular dystrophy are missing or don't have enough of. The hope is this "micro-dystrophin" will at least help slow the progression of the disease.

"I hope that this can extend their lives a little 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 the not walking," Finazzo says. "I just want them to be alive longer. I want them to be alive long enough to enjoy what life is. So if this moves the needle in their life expectancy — even if it does it for a day — it's worth it."

But there's an intense debate about this. Sarepta Therapeutics, the 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 — without direct evidence that's actually helping alleviate symptoms and prevent disease progression.

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

The approval would come through a process known as accelerated approvals. That lets the FDA approve promising treatments quickly before strong evidence is available that the therapy helps, as long as companies promise to then conduct follow-up studies to prove it works.

"We're dealing with a very serious rare disease. A deadly disease. Every day matters to these patients," says Douglas Ingram, Sarepta's CEO. "This could be the most important therapy so far developed for children with Duchenne muscular dystrophy. We have, at least from our perspective, the perfect opportunity to use the accelerated approval pathway."

But this accelerated approval process is controversial because some companies fail to follow-through on their promises to confirm their treatments work. A drug approved this way to prevent premature birth was recently withdrawn after being found useless.

Sarepta's gene therapy for muscular dystrophy would be the first gene therapy approved through the accelerated approval process. And the request has reportedly triggered intense debate within the FDA.

Sarepta has yet to complete the required follow-up studies for three other treatments focused on dystrophin for muscular dystrophy previously approved through the accelerated 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 the disease, she says.

"We're still left uncertain whether or not these very expensive treatments actually yield a meaningful clinical benefit, or if we're just simply still guessing," Ramachandran says.

"This question's been looming since 2016: Is dystrophin an appropriate proxy measure for clinical benefit for Duchenne muscular dystrophy. That's still a looming question. And the fact that it's, you know, seven years later and we still don't have an answer is a bit appalling," she says.

If it turns out not to help, Ramachandran worries the approval could discourage the development of other treatments that could work and preclude patients from being eligible for those therapies.

And then there's the issue of cost. Though the company hasn't released expected costs yet, other recently approved gene therapies have cost as much as $3 million to treat each patient.

The costs, which may not always be covered by insurance, could drain money families could otherwise use for much-needed treatment, such as physical therapy and in-home care-givers, she says.

"That's real harm," she says.

Dr. Glen Nuckolls at the National Institute of Neurological Disorders and Stroke said he couldn't comment directly on Sarepta's request. But he too expressed reservations about relying on a surrogate marker.

"There's certainly data to suggest that you start making dystrophin it's going to result in regeneration of the tissue and increased strength. But I think the relationship of what exact level is needed, we'd probably like to have some more data on that," Nuckolls says.

But Ingram, Sarepta's CEO, says waiting for more data would come with a cost.

"During that period of waiting, some six to 800 kids will die. Some 600 to 800 kids will be consigned to a power wheelchair for the rest of their lives. Six hundred to 800 kids will be consigned to permanent ventilation," Ingram says. "All of these kids ... will be irreparably damaged in ways we won't be able to reverse."

The company says it has preliminary data indicating the gene therapy is helping patients, and already has a big study to confirm those finding well underway.

The company's request is being supported by groups like the Muscular Dystrophy Association.

"Surrogate endpoints like dystrophin measurements allow more access," says Dr. Barry Byrne from the University of Florida, the association's chief medical advisor. "An analogy would be a drug that lowers cholesterol is expected to have an improvement in cardiovascular mortality. So it's a similar analysis."

"We believe that it is slowing the disease and hopefully stabilizing these patients," says Debra Miller, who heads CureDuchenne, a patient advocacy group that helped fund Sarepta. "We have high hopes that at least for many years we'll be able to arrest the downward progression of this disease through gene therapy."

For her part, Susan Finazzo knows it's possible the drug won't help her sons, but she's hopeful.

"I'm just so excited that we even got the opportunity to take part in this [study]. Because the majority of the kids can't. So this is this is an amazing opportunity," she says.

Each year at her sons' birthdays, she's reminded of how little time they have to help them.

"Birthdays are especially hard because they're bitter sweet," Finazzo says. You're so happy but then you're also knowing that that's one less year with them. That's just a reminder of the clock's that ticking."

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