Gene therapy has seemed out of reach for decades. Yet advocates have considered it a way to have damaged or missing genes restore dystrophin and other proteins. Doctors and advocates consider the treatment as a medical breakthrough.
FDA’s Outside Advisors
According to a report in Reuters, on May 12, 2023, a group of advisors to the FDA voted to recommend that it grant Sarepta Therapeutics accelerated approval for its gene therapy to treat Duchenne muscular dystrophy (DMD).
Based on somewhat limited data, eight advisors voted for accelerated approval of the investigational drug SRP9001 while six advisors voted against it. The FDA typically follows its advisors’ advice but is not under any obligation in this regard.
To head off further concerns, Sarepta’s ongoing confirmatory trial will detail the actual benefits of the therapy. Initial data from this trial is expected to be released in December while additional results will be released in early 2024.
Tabassum Ahsan, who chaired the panel, commented that the ongoing confirmatory trial should have a decided influence. Although the midstage trial produced a smaller version of the dystrophin protein, one of the main goals, a benefit to muscle function, was not achieved. The participants showed no improvement in their ability to walk or stand.
Several advisers said that they had concerns and were waiting until they had more evidence to move forward. The FDA also suggested that the data produced by Sarepta lacked sufficient evidence to prove the therapy will benefit DMD patients.
Yet, Peter Marks, a top FDA official noted that a number of advisors were of the belief that with the help of a confirmatory trial, there may be enough evidence to move forward.
NORD estimates that DMD affects one male birth in 3,500 worldwide. Most DMD patients lose their ability to walk by the time they are in their teens and eventually succumb to the disease within twenty to thirty years.
SRP-9001 was invented at the Nationwide Children’s Hospital in Columbus, Ohio. It was then licensed and developed by Sarepta. The therapy delivers a somewhat smaller version of the dystrophin gene to the cells. Viruses are used to transport copies of genes to muscles and replace missing or damaged genes with the goal of developing a comparable version of the protein.
Sarepta’s other currently approved DMD therapies only treat a portion of patients who have specific gene mutations. Other available therapies include side effects such as corticosteroids (causing weight gain) or osteoporosis if used long-term.
Living But Not Suffering
Melanie Hennick spoke during the public portion of the FDA advisor’s meeting. Melanie was joined by other parent advocates who were in favor of accelerating approval for SRP-9001.
Her son Connor was one of the children who received the SRP-9001 therapy with the goal of either slowing or stopping the progression of the disease. Current treatments which include steroids and heart drugs have thus far been ineffective.
Melanie said that she knew the therapy would not cure twelve-year-old Connor. She expressed her relief that although he is still ‘living’ with the disease he is not ‘suffering’ and said there has been a significant difference.
Other families who took part in Sarepta’s trials were in disagreement with the reviewers. These families were convinced that their child would not be running and walking without the benefit of Sarepta’s therapy.
Initial data from the confirmatory trial, study 301, will be available in December.