Members of the Peripheral and Central Nervous Systems Drugs Advisory Committee concluded that there currently is insufficient clinical evidence for the use of drisapersen (Kyndrisa) for the treatment of Duchenne muscular dystrophy in patients with mutations amendable to exon 51 skipping.
The drug, developed by BioMarin Pharmaceutical, is one of two that are currently in development for the rare neuromuscular disorder.
In its review, the committee expressed concern over the drug’s seemingly insignificant effect on dystrophin levels, which is its main mechanism of action. Even after treatment with drisapersen, dystrophin levels remained within the range seen in untreated patients with Duchenne muscular dystrophy (DMD), the committee noted.
The committee also criticized results from the drug’s 3 controlled studies, calling the results “inconsistent.” They also highlighted concerns over the drug’s safety profile, including a severe risk of renal injury, thrombocytopenia, vascular injury, and dermal toxicity.
Stopping short of recommending that drisapersen not be approved, the committee recommended that BioMarin conduct additional studies in children aged 5 years and younger to establish positive findings on clinically meaningful endpoints. Once efficacy is established, the drug’s benefit-risk needs to be reassessed with consideration for patients’ risk tolerance, disease stage, and severity.