Nationwide Children’s Hospital neurologist helps develop gene therapy to treat Duchenne Muscular Dystrophy

The Food and Drug Administration Thursday approved the first gene therapy treatment for Duchenne Muscular Dystrophy, a progressive disorder that typically robs boys of their ability to walk around age 10 and often kills them in their teens or 20s.

The therapy was approved solely for boys ages 4 and 5 with a specific genetic mutation and no medical condition that precludes treatment.

The drug, called Elevidys, is made by Sarepta Therapeutics, of Cambridge, Massachusetts, which announced Thursday that it would charge $3.2 million for the therapy, which it hopes will be a one-time treatment. Other gene therapies approved in recent years have been priced as high as $3.5 million.

Although limited for now, advocates hope this approval will be the first of several gene therapies to treat the underlying cause of the disease, which affects about 12,000 to 15,000 children and adults in the United States and about 300,000 worldwide.

The dystrophin gene sits on the X chromosome. Females typically have two X chromosomes, so if one has the faulty gene, the other can compensate. Males only have one X chromosome, so they can't adjust and are far more likely to develop Duchenne's.

Previous treatments, including steroids and exercise, have slowed progression of muscle weakness, but not changed the disease's course. Another therapeutic approach, called antisense oligonucleotides, can only address a minority of patients and has to be given repeatedly.

"Today's approval addresses an urgent unmet medical need and is an important advancement in the treatment of Duchenne muscular dystrophy, a devastating condition with limited treatment options, that leads to a progressive deterioration of an individual's health over time," Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said in a statement.

It delivers a gene that leads the body to produce a shortened form of the dystrophin protein that boys with the disease are missing. Without that protein, muscles can't repair themselves and damage accumulates over time.

Three other companies are also developing gene therapies for Duchenne's, each with slightly different approaches. Several participants in other trials have died, raising concerns about the safety of the approach.

It's not clear with Duchenne's, which involves the muscles of growing children, whether one treatment will be enough to last a lifetime.

The drug was approved under a so-called accelerated approval pathway, which provides earlier access to a drug while a company continues clinical trials to confirm benefits.

Patient advocacy groups, including the Muscular Dystrophy Association and CureDuchenne, which helped fund the research leading to gene therapy, praised the decision Thursday and said they anticipate more approvals to come for Duchenne therapies.

"We recognize that many in the community will be disappointed due to the narrow age range specified," CureDuchenne CEO Debra Miller said in an emailed statement. "While this is a significant milestone, our work is far from done. There are still many individuals waiting for effective treatments, and CureDuchenne will continue to support and invest in a diverse array of promising research to bring solutions to everyone living with Duchenne, including many technologies that could potentially overcome the limitations of first-generation gene therapies."

Neither advocacy group seemed surprised by the high price tag.

"MDA will stand shoulder to shoulder with the Duchenne community in advocating for affordable access for every eligible child with Duchenne as soon as the therapy is available,” Muscular Dystrophy Association vice president of public policy and advocacy Paul Melmeyer said in an email.

But an organization called Doctors for America, which includes 27,000 doctors and medical students, came out against the approval, saying the FDA should have waited for the completion of clinical trials to confirm that the therapy's benefits outweigh its risks.

"Gene therapies offer incredible promise, but there must be careful consideration of these novel treatments especially when being considered for approval for use in young people, where safety concerns may manifest after the clinical trial period," according to a press release from the organization.

Once a drug receives FDA approval, even for a specific group, it can be prescribed off-label to others, the group warned, "subjecting patients looking for hope to an unproven and expensive treatment."

The FDA's decision, the group said, "lowers the bar on innovation and may waste precious time if companies follow suit and develop similar therapies of uncertain benefit. "

Patients who take Elevidys might also be unable to get other, perhaps better, gene therapies later on, though companies are working to figure out a way to redose gene therapies if needed.

The approval was based on data from a trial that showed Elevidys increased production of the missing protein, which the FDA determined was reasonably likely to predict a clinical benefit for boys ages 4 and 5. The study did not show the boys had improved motor function.

Side effects of the treatment include vomiting, nausea, liver injury, fever and low blood platelet counts.

As a condition of approval, the company must complete a clinical study to confirm the drug's benefit, including improving physical function and mobility in DMD patients who can still walk. That study has already begun.

Dr. Jerry Mendell, who co-invented the gene therapy, said "treating boys with Duchenne muscular dystrophy after seeing their natural history and decline over and over and over for the past 50 years, it was the most gratifying thing I've ever been a witness of."

Mendell, a pediatric neurologist and principal investigator in the Center for Gene Therapy at Nationwide Children’s Hospital, began using the therapy now called Elevidys in 2017. He treated four boys, ages 4 to 6.

"It's now five years later and they're doing very, very, very well," Mendell said. "They can ride bikes now. They can play in the playground. They can run and participate with peers in many ways they couldn't do before. … That's contributing to a real meaningful life."

A similar study in older boys was not able to prove effectiveness, Mendell said, but he is confident such proof will come.

He also hopes that the existence of a truly effective therapy for Duchenne's will lead to newborn screening for the disease and the start of treatment at a much younger age. "If we can get to the disease before it has any devastating effects, it's much more likely to show even more profound efficacy," Mendell said.

Contact Karen Weintraub at kweintraub@usatoday.com.

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This article originally appeared on USA TODAY: Local neurologist develops approved gene therapy treatment for Duchenne Muscular Dystrophy