Sarepta Therapeutics has ceased the development of vesleteplirsen (SRP-5051), an antisense oligonucleotide (ASO) treatment for Duchenne muscular dystrophy (DMD). The decision was influenced by an updated risk-benefit analysis, feedback from the U.S. Food and Drug Administration (FDA), and the evolving therapeutic landscape for DMD.
Vesleteplirsen was designed as an improved version of eteplirsen, targeting exon 51 skipping to enhance dystrophin production in DMD patients. Eteplirsen, Sarepta's first exon-skipping ASO, received FDA approval in 2016 after considerable debate but was rejected by the EMA due to concerns about clinical evidence and cost.
The Phase 2 Momentum trial of vesleteplirsen was placed on hold by the FDA in 2022 after patients experienced hypomagnesemia, leading to muscle weakness, seizures, and irregular heart rhythms. Some patients also showed a decrease in kidney function, as measured by estimated glomerular filtration rate (eGFR).
"Safety is our number one priority," Sarepta stated in a letter to the Duchenne community. "Considerations about long-term safety and tolerability led to the decision to discontinue development of SRP-5051… We recognize this news may be deeply disappointing for the Duchenne community, especially those who have participated in studies of SRP-5051."
Sarepta currently markets three exon-skipping ASOs: eteplirsen (targets exon 51), golodirsen (targets exon 53), and casimersen (targets exon 45). These treatments address DMD symptoms but do not provide a cure. In addition, Sarepta's gene therapy Elevidys (delandistrogene moxeparvovec-rokl) received full FDA approval this summer, although it missed its primary endpoint in a Phase 3 trial.
The company will continue to advance other molecular candidates, including late-stage gene therapies for limb-girdle muscular dystrophy, with a potential submission for approval anticipated next year.
