The FDA's decision in June 2024 to expand the approval of delandistrogene moxeparvovec-rokl (ELEVIDYS), a gene therapy for Duchenne muscular dystrophy (DMD), has ignited controversy due to concerns over efficacy and the process behind the approval. The expanded approval now includes ambulatory individuals four years of age and older with a confirmed mutation in the DMD gene, as well as accelerated approval for wheelchair-dependent individuals in the same age group.
DMD is a rare and devastating genetic condition primarily affecting males, with an incidence of approximately 1 in 5,000 live male births. The disease leads to progressive muscle weakness and wasting, typically causing gait disturbances by age five and wheelchair dependence by age 13.
The initial accelerated approval of ELEVIDYS in June 2023 for ambulatory children aged four to five was already met with skepticism. The subsequent expansion, particularly to include non-ambulatory patients, has amplified these concerns. A pivotal randomized clinical trial designed to confirm the gene therapy's clinical benefit failed to meet its primary endpoint, which assessed motor function improvement compared to placebo in ambulatory males with DMD.
ELEVIDYS, an adeno-associated virus vector-based gene therapy, comes with a hefty price tag of $3.2 million for a single intravenous infusion, making it one of the most expensive drugs globally. Furthermore, patients receiving ELEVIDYS may develop antibodies to the adeno-associated virus vector, potentially precluding them from receiving other gene therapies in the future.
Critics, including some within the FDA, argue that the expanded approval was based on "convoluted reasoning" rather than robust scientific evidence. They suggest that the FDA should have maintained the accelerated approval for specific patient subgroups with promising but inconclusive evidence of benefit, while requiring the manufacturer to conduct additional placebo-controlled trials.
The controversy surrounding ELEVIDYS highlights the challenges of balancing the urgent need for treatments for rare diseases with the necessity of upholding rigorous scientific standards in drug approval processes. The FDA's decision has prompted calls for a review of its internal procedures to ensure the integrity of the approval process and maintain public trust.
