CNN
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The US Food and Drug Administration has given the green light for the first gene therapy to treat a rare form of muscular dystrophy to be used in most people who have the disease and a certain genetic mutation.
Last year, the drug – Elevidys, from the biotech company Sarepta Therapeutics – was approved to treat only children aged 4 and 5 with Duchenne muscular dystrophy, one of the most severe forms of the inherited muscular dystrophies, who have a mutation of confirmed in a gene called DMD related to muscle strength.
The FDA announced Thursday that it had granted traditional approval for Elevidys for ambulatory people 4 years of age and older with a confirmed mutation in the DMD gene and accelerated approval for non-ambulatory people 4 years of age and older with this mutation. There are not enough safety data to support its use in children under 4, the agency says.
Elevidys, given as a one-time intravenous infusion, costs about $3.2 million per patient. While eye-catching, such a price tag is not out of step with other one-time gene therapies, which have topped $3 million per patient in recent years. But Elevidys appears to be the second most expensive drug in the world, behind the $3.5 million hemophilia treatment Hemgenix.
Elevidys was previously approved under the FDA’s accelerated approval pathway, which clears drugs for diseases where they are urgently needed, based on data suggesting they are likely to provide clinical benefit. The drug has been closely monitored since that approval, and in October, Sarepta Therapeutics released results from a confirmatory trial showing that the therapy missed its primary goal—a measure of how well children can move—but was successful on a number of secondary measures.
Approval addressed “An urgent unmet medical need and is an important advance 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 news release at the time.
It was the first time a therapy of this nature – a one-time treatment that delivers a working copy of a gene to compensate for the one that leads to the disease – had been cleared under the accelerated approval framework. The move came after emotional testimony from families at an FDA advisory committee meeting.
Duchenne muscular dystrophy causes progressive muscle weakness that can rob children of their ability to walk by the time they are teenagers, and many do not live well into their 30s. It mainly affects boys because of the way it is inherited, affecting about 1 in 3,300 boys.
The Muscular Dystrophy Association trusts the FDA’s decision, which weighs the drug’s risks and benefits, said Dr. Sharon Hesterlee, principal investigator at the association.
“At the end of the day, what we want is what’s best for our patient community — and that’s the right balance of risk-benefit,” she said.
Potential risks of Elevidys include increased levels of certain liver enzymes and serious acute liver damage. The most common side effects of the drug include vomiting, nausea, increased liver function tests, and fever.
However, a major benefit is that gene therapy offers another option for people with Duchenne muscular dystrophy, and it is only administered once.
There is no cure for Duchenne muscular dystrophy and outside of Elevidys, treatments are limited. Other approaches may include steroid medications, certain drugs that change the way muscle cells “read” the mutated gene, physical therapy or surgery to correct the curvature of the spine, Hesterlee said.
“Right now, the main standard of care for Duchenne is corticosteroids, such as prednisone, although there are some newer drugs available. These children are still often on chronic doses of steroids for many, many years,” she said, adding that the side effects of corticosteroids — such as weight gain, behavioral problems and an increased risk of bone fractures — are not ideal.
Duchenne muscular dystrophy can be difficult to treat, she said, and having more treatment options that have been proven to be effective remains important.
“Muscles make up a significant amount of your body mass. So when you have a disease like this, it really affects many tissues. So whatever you do, you’re trying to reverse or stop a disease process that’s really throughout the body, and it’s a disease that’s progressive, so you lose more and more muscle over time,” he said. Hesterlee.
“It made it quite challenging, but we certainly learned a lot,” she said. “You can’t ignore the fact that these guys are living a lot longer and doing a lot better. Even 20 years ago, they were dying in their teens and many are now living into their 30s. They will go to college; they have girlfriends; some of them are married. These are things that did not happen years ago. So we’ve made tremendous progress.”