Sarepta Therapeutics has announced positive data from the previously halted second part of a Phase II study investigating vesleteplirsen in patients with Duchenne muscular dystrophy (DMD).
Sarepta Therapeutics’s executive vice president Dr Louise Rodino-Klapac says that the favourable data from the Momentum study (NCT04004065) will help in discussing the next steps with the FDA.
At a high dose of vesleteplirsen (30mg/kg) every four weeks, patients achieved a mean dystrophin expression of 5.17%, and mean exon skipping of 11.11% at 28 weeks. This is compared to a 2.81% mean dystrophin expression and mean exon skipping of 2.47% in the low-dose cohort (20mg/kg) every four weeks.
In the high-dose cohort, changes from baseline represented a 12.2-fold increase in dystrophin expression and a 24.6-fold increase in exon skipping compared to a weekly 30mg/kg dose of the current standard of care (SoC) Exondys 51 (eteplirsen) at 24 weeks. The low-dose cohort changes represent a 4.3-fold increase in dystrophin expression and a 4.9-fold increase in exon skipping compared to Exondys 51.
There were seven serious, treatment-emergent adverse events (TAEs) in the second part of the study; four serious events of hypomagnesemia and three serious cases of hypokalemia. Hypomagnesemia is a known adverse event (AE) which has been identified in earlier studies.
In June 2022, the FDA halted part two of Sarepta’s trial due to the serious AE of hypomagnesemia. In September, the trial continued after Sarepta changed the protocol and agreed to provide supplemental magnesium.
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There were no treatment-related discontinuations during the trial.
The global, Phase II, multi-ascending dose trial of vesleteplirsen enrolled patients with DMD amenable to exon 51-skipping treatment aged between eight and 21 years.
Patients in the trial were infused every four weeks, and investigators assessed dystrophin protein levels in skeletal muscle tissue. The study also assessed safety and tolerability. The second part of the study enrolled 40 patients, both ambulant and non-ambulant, across 25 sites in the US, Canada, and Europe.
Vesleteplirsen is a next-generation peptide phosphorodiamidate morpholino oligomer (PPMO) treatment.
Both Exondys 51 and vesleteplirsen skip exon 51 in the dystrophin gene which can assist around 13% of DMD patients.
Sarepta has faced hurdles in DMD trials
Sarepta has faced a rocky road in its trials of various DMD treatments but has a number of candidates in the pipeline and on the market.
Exondys 51, which is also marketed by Sarepta, received accelerated approval by the FDA as the first drug to treat DMD. This came despite calls from the Peripheral Central Nervous System Drugs Advisory Committee of the FDA to not approve the treatment, citing that several studies failed to meet their primary endpoints.
Sarepta suffered a recent hit with its DMD gene therapy after receiving accelerated approval for Elevidys in June 2023. Just a few months later, the company announced negative Phase III results showing the candidate failed to improve muscle function compared to a placebo.
GlobalData predicts a sales forecast for vesleteplirsen of $183m in 2027. The total market value for DMD in the same year is predicted to be $6.9bn.
GlobalData is the parent company of the Clinical Trials Arena.