CNN
—
Most parents wouldn’t be thrilled with the idea of their children hooked up to an IV bag filled with trillions of viruses.
But for Melanie Hennick, whose son, Connor, has Duchenne muscular dystrophy, it was an opportunity she hoped would change her life.
“We knew this was not a cure,” Hennick said. “But it was an opportunity.”
Connor is one of dozens of children who have received SRP-9001, an experimental gene therapy that is intended to slow or stop the progression of Duchenne muscular dystrophy, or DMD. Current treatments for the disease, which mainly affects children because of the way it is inherited, include steroids and, later, heart medications. But no one stops him.
SRP-9001 uses viruses to transport a copy of a gene into the muscles to help compensate for the one that is causing the disease. Hennick and many other parents like her advocated for expedited approval of the treatment Friday at a meeting of outside advisers to the US Food and Drug Administration.
The advisers voted 8-6 to approve the treatment and the FDA will now decide whether to follow their advice.
“The decision that the FDA has to make does not only affect the patients of the 301 study [an ongoing confirmatory trial that Sarepta is running]; it affects the entire field of Duchenne drug development,” said Dr. Caleb Alexander, professor of epidemiology and medicine at the Johns Hopkins Bloomberg School of Public Health, who voted against recommending approval. “The totality of the evidence … just doesn’t meet the threshold required for expedited approval.”
Dr. Raymond Roos, a professor of neurology at the University of Chicago Medical Center, voted in favor. “The downside of gene therapy here is relatively small compared to whether it actually helps the patient, and for this reason, I voted yes,” he said.
Dr. Peter Marks, director of the FDA’s Center for Biological Research and Evaluation, said his agency will take the recommendation and “do something that we have to do every day at the FDA. … We have to manage uncertainty here.”
The FDA’s decision, expected by the end of the month, will have implications not only for families like Connor’s, but also for how the agency regulates treatments like this more broadly: It would be the first of its kind drug: unique treatments that provide a gene to try to correct a disease: to get expedited approval, a faster path through the regulatory process. Its approval would set a precedent for other drugs like this one based on so-called surrogate endpoints, a measure of what the drug does in the body, before more clinical evidence is available.
“The approval of a gene therapy for Duchenne muscular dystrophy is going to be huge,” said Jeffrey Chamberlain, a professor at the University of Washington School of Medicine who helped pioneer gene therapy approaches for the disease. “I think this will drive more research and further development of gene therapies for other diseases.”
DMD patients do not have long to wait. Boys with Duchenne usually lose the ability to walk before their teens and often don’t live well into their 30s, Chamberlain said. He is not directly involved with SRP-9001, which is being developed by Sarepta Therapeutics, and is on the scientific advisory board of another company working on gene therapies for DMD, Solid Biosciences.
“Gene therapy seems to be a really good approach to treat this disease, because it’s a genetic disease,” Chamberlain said. “The cause of the disease is a mutation in a single gene.”
That gene is responsible for the production of dystrophin, a key protein for the structure of muscle cells.
“It’s kind of like the two by four that make up your house,” Chamberlain said. “It’s really important to keep everything together.”
SRP-9001, invented at Nationwide Children’s Hospital in Columbus, Ohio, prior to being licensed for development by Sarepta, delivers a miniaturized version of the dystrophin gene to cells, with the goal of helping them produce a version of the protein that preserves the muscles.
in a key clinical trial, therapy seemed to do that. But it failed to meet another primary goal: to show a benefit in a measure of muscle function, complicating SRP-9001’s path through the FDA.
Sarepta blamed the result on an imbalance in the way the trial separated patients into placebo and treatment groups. But the FDA’s key reviewers seem unconvinced.
“Clinical studies conducted to date do not provide unequivocal evidence that SRP-9001 is likely to be beneficial for outpatients with DMD,” the agency reviewers wrote in information documents posted ahead of Friday’s meeting, referring to patients who can still walk, the group that will initially be eligible for treatment if approved.
Family after family who participated in the Sarepta trials, like the Hennicks, disagree with the reviewers. They say they believe the treatment has helped their children continue to walk and run in ways they never would have without it.
“It’s really miraculous,” said Nate Plasman, whose son Andrew received SRP-9001 as part of the trial in January 2019, at age 4.
Andrew was out of school for more than two months when he received the experimental therapy, Plasman said, and when he returned, “his teachers at the preschool were blown away,” he recalled. “They’re like, ‘Who is this kid?’ He is running. he is jumping he is pedaling the tricycle. He’s getting up and down off the ground” – all things he couldn’t do as well before therapy.
Marit Sivertson, mother of 9-year-old Brecken, agrees.
“We have seen incredible changes with our son,” she said. “He’s not just walking. He is running; He is swimming; he is diving. He really is living the life that every 9-year-old should live.”
Sivertson and Plasman also spoke at the meeting on Friday. Her goal is not to secure therapy for her own children; because it is designed as a one-time treatment, they would not take it again. They say they are speaking on behalf of the children who are still waiting.
That wait is especially painful for Daniel and Lindsey Flessner, who have two children with DMD. Her 5-year-old son, Mason, is participating in the SRP-9001 clinical trial. Their 2-year-old son, Dawson, is still too young.
“With every ride, every fall, every time you stand up with your hands up to help stabilize yourself, it continues to affect us,” Flessner said. “It is very painful for parents to see their children struggle knowing that all they can do is wait, when waiting is what they don’t have time for.”
In addition to questions about how well the treatment works, the FDA reviewers raised safety concerns, particularly “in relation to the possibility of delivering ineffective gene therapy.”
The reviewers focused on the opportunity cost: due to the viruses used to deliver the gene, patients may develop an immune response that could render future doses ineffective.
Chamberlain said work is underway to find ways to be able to give more doses, if needed, but it’s currently a single treatment.
For now, he believes this approach is the best hope for DMD patients.
“It’s not perfect,” he acknowledged. “It’s not a complete cure, but from what I can gather from the clinical results published by Sarepta and some of the other companies, I think microdystrophin gene therapy is working better than any other drug that’s been tried for Duchenne. muscular dystrophy.”
It’s unclear how long the effects will last; Sarepta is continuing trials and a confirmatory study would be required as part of accelerated approval. Sarepta has proposed a test that is already running to satisfy that requirement, with results expected later this year.
For families dealing with DMD, waiting also has an opportunity cost. In its information documents For the FDA meeting, Sarepta estimated that accelerated approval would speed up widespread access to SRP-9001 by at least a year, by which time some 400 children could lose the ability to walk and another 400, whose disease is more advanced, they would die
Melanie Hennick said that Connor was admitted to the trial only weeks before he would have reached the age of majority, at 8 years old. She said that she believes therapy is the reason Connor is doing so well.
“We got to see Connor grow up as an 8, 9, 10, 11, 12-year-old with more ability than we ever dreamed of,” he said. “Climbs stairs without help; he runs around; He plays football; he plays hockey; he plays on a baseball team. … Those are things we never thought we would be able to see him do, especially at 12 years old.”
—————————————————-
Source link