Families facing rare muscle disease are pushing for an experimental gene therapy, but the FDA is skeptical

Families facing rare muscle disease are pushing for an experimental gene therapy, but the FDA is skeptical


Parents would be hesitant to allow their children to have an IV bag containing trillions of virus.

Melanie Hennick's son Connor has Duchenne muscular Dystrophy. She hoped that this opportunity would change his future.

Hennick stated, "We knew that this was not a cure." But it was a shot.

Connor is just one of a handful of children who have received SRP 9001, a gene therapy designed to slow down or stop the progression Duchenne muscular Dystrophy (DMD). The disease, which is inherited more commonly in boys, can be treated with steroids, and later heart drugs. But none of them stop it.

SRP-9001 is a treatment that uses viruses to deliver a copy of the gene to muscles in order to compensate for a gene that causes the disease. Hennick and other parents, like her, are advocating today for the treatment to be approved acceleratedly in a meeting with outside advisers of the US Food and Drug Administration.

The FDA will then decide if they will follow the advice of the advisers. The FDA decision is expected to be made by the end this month. It will impact not only families like Connor’s, but also how the FDA regulates treatments such as this one. This would be the very first medicine of its type - a one-time treatment delivering a specific gene to treat a particular disease - that gets accelerated approval. The FDA's decision, expected by the end of the month, will have implications not only for families like Connor's but also how the agency regulates treatments such as this one more broadly: It would be the first medicine of its kind - one-time treatments delivering a gene to try and fix a disease – to get accelerated approval, a faster track through the regulatory process.

Jeffrey Chamberlain is a professor of medicine at the University of Washington School of Medicine. He helped pioneer gene therapies for this disease. This, I believe, will encourage further research and development of gene therapy for other diseases.

DMD patients do not have much time to wait. Chamberlain says that kids with Duchenne lose their ability to walk by the time they are teenagers. They also don't usually live past 30. Chamberlain is not directly involved in the development of SRP-9001 by Sarepta Therapeutics. He is, however, on the scientific board for Solid Biosciences, a company that is working on DMD gene therapy.

Chamberlain stated that 'Gene Therapy appears to be an excellent approach to treating this disease because it is a genetic disorder'. The cause of this disease is a gene mutation.

This gene is responsible to produce dystrophin. Dystrophin is a key protein in the structure of the muscle cells.

Chamberlain explained that it's like the two-by fours that you use to build your home. It's important to keep everything together.

SRP-9001 was developed by Sarepta after being invented at Nationwide Children's Hospital, Columbus, Ohio. It delivers a miniature version of dystrophin to the cells to encourage them to produce a version the muscle-preserving proteins.

The therapy seemed to achieve this in a major clinical trial. It didn't achieve another major goal, which was to show a benefit in a measure for muscle function. This complicated SRP-9001’s FDA approval.

Sarepta blamed an imbalance in the way the trial divided patients into placebo and treatment groups. But key FDA reviewers appear unconvinced.

In briefing documents distributed ahead of the Friday meeting, agency reviewers stated that 'the clinical studies conducted so far do not provide clear evidence that SRP 9001 is beneficial for ambulatory DMD patients'. They were referring to the patients who are still able to walk, the first group to be eligible for this treatment, if it's approved.

Families who took part in the Sarepta trials, including the Hennicks family, have disagreed with the reviewers. They believe the treatment helped their children walk and run in ways that they would not have been able to do without it.

Nate Plasman's son Andrew, who was 4 years old when he received SRP-9001 in the January 2019 trial, said, "It is really miraculous."

Plasman stated that Andrew had been away from school for over two months before he received the experimental treatment. When he returned to preschool, "his teachers were blown away," he said. He is pedaling his tricycle. He can now get up and down from the floor.

Marit Sivertson agrees with her daughter Brecken, who is nine years old.

She said, "We've seen incredible changes in our son." He is truly living the life every nine-year-old should be living.

Sivertson, Plasman and others are speaking today. They don't want to get the treatment for their children; it is a one-time therapy, so they won't do it again. They claim to be speaking for children who have yet to receive treatment.

Daniel and Lindsey Flessner have two DMD-affected sons. Mason, their 5-year-old, is a participant in the SRP 9001 clinical trial. Dawson, their 2-year-old son, is too young.

Flessner stated that 'every trip, every fall and every time he stood up using his hands to stabilize him just kept chipping away at our hearts'. It's painful to watch your child struggle, knowing that all you can do is sit and wait. But you have no time for waiting.

The FDA also raised safety concerns, namely'relative to the possible administration of an ineffective genetherapy'.

Reviewers concentrated on the opportunity cost. Patients can develop an immunity response to the virus used to deliver the genes, which could make future doses ineffective.

Chamberlain stated that work is being done to find a way to administer additional doses if necessary, but for now, it's a one-and -done treatment.

He believes that this is the best approach for DMD sufferers at the moment.

He acknowledged that it was not perfect. It's not a cure but, based on the clinical data released by Sarepta, and other companies, the micro-dystrophin therapy seems to be working better than other drugs that have been tested for Duchenne muscular Dystrophy.

Sarepta continues its trials and would need to conduct a confirmatory trial as part of an accelerated approval. Sarepta is already running a trial to meet this requirement. Results are expected later in the year.

Waiting can also be costly for families with DMD. Sarepta's briefing materials for the FDA meeting estimated that accelerated approval could speed up access to SRP 9001 by at least a full year. During this time, 400 boys who have advanced DMD would lose their ability to walk and 400 others would die.

Melanie Hennick stated that Connor had been admitted to the trial only a few weeks before he would have reached his age limit, which was 8 years. She believes that Connor is doing well because of the therapy.

'We were able to watch Connor develop as a child of 8, 9, 10, 11, and 12 years old with greater capacity than we could have imagined,' said the mother. He runs, he climbs the stairs without assistance. He plays football, he also plays hockey and he is on a baseball squad. We never imagined that he would be able do those things, even at 12 years old.