Sarepta Therapeutics has announced the discontinuation of its vesleteplirsen program, a next-generation exon-skipping drug intended as a successor to Exondys 51 (eteplirsen) for Duchenne muscular dystrophy (DMD). The decision, revealed during the company's third-quarter results update, reflects a strategic reassessment of the program's risk-benefit profile in light of FDA feedback and the shifting therapeutic landscape for DMD.
Vesleteplirsen (formerly SRP-5051) was designed to improve upon Exondys 51 by increasing tissue penetration and exon-skipping potency, thereby boosting dystrophin protein production, which is deficient in individuals with DMD. Exondys 51 is an exon-skipping therapy applicable to approximately 13% of the DMD population.
The development of vesleteplirsen encountered significant hurdles, including a clinical hold imposed by the FDA in 2021. This hold was a consequence of hypomagnesaemia observed in a clinical trial participant, a condition characterized by very low magnesium levels that can lead to muscle weakness, tremors, seizures, and irregular heart rhythms.
Sarepta's portfolio of exon-skipping therapies, including Exondys 51, Vyondys 53 (golodirsen), and Amondys 45 (casimersen), has been a key revenue driver for the company. However, the recent FDA approval and expanded label for Elevidys (delandistrogene moxeparvovec), Sarepta's gene therapy for DMD, is rapidly changing the company's revenue dynamics. The expanded label allows for the treatment of both ambulatory and non-ambulatory boys aged four and above with DMD, without an upper age limit.
In the third quarter, Elevidys generated $181 million in revenue, while the combined sales of Exondys 51 and its sister exon-skipping drugs totaled $249 million. Sarepta also reported approximately $10 million in royalties from Roche related to ex-US sales of Elevidys. Overall, Sarepta's revenues increased to $428 million, up from $332 million in the same quarter of the previous year. According to Sarepta CEO Doug Ingram, the rise in revenue indicates that the gene therapy is not cannibalizing sales of its exon-skipping drugs.
Sarepta is also advancing other R&D programs, including two gene therapy candidates for limb-girdle muscular dystrophy, with one slated for filing by mid-2025.
