Duchenne muscular dystrophy and the accelerated approval debate
No paediatric disease has tested the FDA’s accelerated approval pathway like Duchenne. The arguments over dystrophin, function and risk are far from settled.
In brief
Duchenne muscular dystrophy has tested FDA accelerated approval like no other disease, from eteplirsen to micro-dystrophin gene therapy.
Duchenne muscular dystrophy (DMD) is a genetic disease, overwhelmingly affecting boys, caused by mutations in the gene for dystrophin, a protein that protects muscle fibres. Without it, muscles degenerate. Children typically lose the ability to walk by their early teens, and heart and breathing muscles are affected later.
Exon skipping and the surrogate question
In 2016 the FDA granted accelerated approval to eteplirsen, an antisense drug that skips exon 51 of the dystrophin gene, allowing some patients to make a shortened but partly functional protein. The approval was based on small increases in dystrophin measured in muscle biopsies, and it was controversial within the agency itself. Further exon-skipping drugs targeting other exons followed.
The central dispute was whether small increases in dystrophin were reasonably likely to predict clinical benefit. Confirmatory trials were required to answer it.
Gene therapy
In 2023 the FDA granted accelerated approval to delandistrogene moxeparvovec, a gene therapy delivering a shortened “micro-dystrophin” gene, for ambulatory boys aged four and five. In 2024 the label was broadened following further review, despite a confirmatory trial that missed its primary endpoint. In 2025, reports of deaths from acute liver failure in treated patients led to restrictions and renewed scrutiny of the therapy’s risks.
Other approaches
Not all recent approvals involve gene correction. Vamorolone, a modified steroid intended to retain anti-inflammatory benefit with fewer side effects, and givinostat, a histone deacetylase inhibitor, were approved in 2023 and 2024 respectively.
The wider lesson
DMD shows the tension at the heart of rare paediatric drug development. Families facing a relentless disease press for access to anything that might help. Regulators must weigh that urgency against the risk of approving therapies whose benefit is uncertain and whose risks are not fully known. Each DMD decision has become a reference point in that debate.
