FDA approves US$ 3 million therapy for Duchenne dystrophy – 7/3/2023 – Equilibrium and Health

Last week, the FDA, the regulatory agency in the United States, approved the first gene therapy for the treatment of patients with Duchenne muscular dystrophy, a disease that causes progressive muscle weakness.

Called Elevidys, the therapy has been approved exclusively for 4- and 5-year-olds and will cost $3.2 million, making it the second most expensive gene therapy in the US, behind only of a treatment for hemophilia B, available for $3.5 million.

“The approval addresses an urgent medical need and is an important advance in the treatment of Duchenne muscular dystrophy, a devastating condition with limited treatment options, which leads to a progressive deterioration in an individual’s health over time,” said Peter Marks , director of the FDA’s Center for Biological Evaluation and Research, in a statement released by the agency.

Vice-coordinator of the scientific department of neuromuscular diseases at ABN (Brazilian Academy of Neurology), Alberto Rolim Muro Martinez says that the FDA’s decision was received with surprise and enthusiasm because the agency used an accelerated approval process, which allows providing patients with access to new drugs faster while responsible companies conduct clinical trials to verify effectiveness.

In the case of Elevidys, authorization was granted based on phase 1 and 2 clinical trials, which indicated an increase in microdystrophin protein in 4- and 5-year-old children undergoing the therapy.

These steps, however, did not establish the clinical impact, including whether there is improvement in the children’s motor function. As a condition of approval, the FDA is requiring Sarepta Therapeutics to complete a Phase 3 study to confirm the drug’s benefits. The trial is underway with 126 patients, and the results should be released by the end of the year.

“The agency will review data from this trial as soon as possible to consider whether further actions, such as a revised indication or withdrawal of Elevidys [do mercado]may be necessary,” the FDA said.

What is Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy is a genetic disease that affects mostly males, with approximately 1 case in every 5,000 boys.

It is caused by a lack of a protein called dystrophin, which helps connect muscle cells to their surroundings, and the first symptoms appear around age 3.

Without enough dystrophin in the muscles, they become more rigid, with impaired movement and cardiac and respiratory function. Over time, the person loses the ability to walk and even breathe on their own.

There is no cure, but surgeries and the use of corticosteroids have helped alleviate some symptoms and contributed to increasing the lifespan of patients. Today, some of them even live to be 40 years old.

How does the new therapy work?

The gene responsible for dystrophin production is the largest in the human genome, with about 2.3 million nitrogenous bases. Due to its size, it is not possible to transport it in gene therapy vectors —viruses modified in the laboratory that carry genes inside cells—, but the researchers found a plan B.

Martinez explains that some patients have a milder version of the disease known as Becker muscular dystrophy. In them, the gene responsible for dystrophin is smaller than the standard.

Scientists spent years researching which parts of this gene were essential to maintain muscle activity and created a version capable of being transported and producing a protein with part of the function of the original dystrophin.

The novelty of the work helps to explain the price predicted by the company. “It is fully understandable that this therapy is not cheap because it is something revolutionary and that helps to make possible several other studies”, says Martinez, “but even so, the value indicated is frightening”.

According to the neurologist, if the therapy has proven its effectiveness, it is expected that the international community will apply pressure to make it cheaper. “It’s something that needs to be discussed between agencies, the medical community, health systems and laboratories,” he says.

“We recently had negotiations in Brazil for the incorporation of Zolgensma, for spinal muscular atrophy”, exemplifies Martinez. With the negotiations, the price was agreed at R$ 5.14 million per therapy, with payments in five equal installments over four years. “It’s a win with a hint of ‘Oh my God, where is this going?’ but it’s a win.”