Sarepta Halts Development, Testing of DMD Therapy SRP-5051

Sarepta Therapeutics has discontinued its vesleteplirsen (SRP-5051) development program, a once-promising exon 51–skipping therapy for Duchenne muscular dystrophy (DMD).

According to a recent press release, this decision was informed by current data, ongoing concerns about safety and tolerability, feedback from the FDA, and the rapidly advancing landscape of DMD treatments.¹

Earlier this year, Sarepta reported positive phase 2 data from the MOMENTUM trial (NCT04004065), which was investigating SRP-5051 among boys and young men with DMD amenable to exon 51 skipping.² At both lower (20 mg/kg) and higher (30 mg/kg) doses, SRP-5051 showed encouraging increases in dystrophin expression and exon skipping—key indicators of the therapy’s efficacy. The higher dose cohort saw a 12.2-fold increase in dystrophin production and a 24.6-fold improvement in exon skipping compared with weekly dosing of Sarepta’s older drug, eteplirsen (Exondys 51). At the time, the benefit-risk profile was viewed favorably, even with the observed cases of hypomagnesemia, which were reportedly manageable with supplementation and close monitoring.

However, as the MOMENTUM trial progressed, new safety concerns emerged.³ Although initial cases of hypomagnesemia were manageable, Sarepta noted that in some patients, these low levels of magnesium—which regulates muscle and nerve function, blood sugar levels, and blood pressure, among other functions—persisted even after stopping treatment. Some participants also showed signs of declining kidney function.

The FDA had previously placed a clinical hold on the trial in 2022 after a severe hypomagnesemia case. Although the hold was lifted later that year, allowing the trial to resume with additional safety measures, concerns remained.

“The decision to discontinue this program has no impact on our other approved therapies and/or clinical study programs, including Sarepta’s PMO exon skipping therapies and Sarepta’s gene therapy,” Sarepta said in a letter to the DMD community.⁴ “We believe the concerns are related to the specific cell penetrating peptide used in SRP-5051. There is no evidence of these safety concerns in the PMO program.”

Parent Project Muscular Dystrophy, a leading nonprofit dedicated to advancing DMD research and care, expressed disappointment over the halted development.⁵

“We are grateful to all the families who have participated in clinical trials with vesleteplirsen, and to the Sarepta team for their work to advance therapy development in Duchenne,” the organization said in a news release. “The discontinuation of a trial is always difficult for our community, but we remain hopeful that the data from this trial will inform other potential treatments and that these experiences will lead us to the day that we end Duchenne.”

Participants enrolled in the MOMENTUM trial are being scheduled for final study visits.³

References

1. Sarepta Therapeutics announces third quarter 2024 financial results and recent corporate developments. News release. Sarepta Therapeutics. November 6, 2024. Accessed November 14, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-third-quarter-2024-financial

2. Shaw ML. Positive phase 2 data for SRP-5051 in Duchenne muscular dystrophy. AJMC^®. February 13, 2024. Accessed November 14, 2024. https://www.ajmc.com/view/positive-phase-2-data-for-srp-5051-in-duchenne-muscular-dystrophy

3. Lobo A. Sarepta stops development of exon 51-skipping therapy for DMD. Muscular Dystrophy News Today. November 12, 2024. Accessed November 14, 2024. https://musculardystrophynews.com/news/sarepta-stops-development-exon-51-skipping-therapy-dmd/

4. Community letter: update SRP-5051 program. Sarepta Therapeutics. November 6, 2024. Accessed November 14, 2024. https://www.sarepta.com/community-letter-update-srp-5051-program

5. Sarepta announces discontinuation of SRP-5051 development for Duchenne. News release. Parent Project Muscular Dystrophy. November 6, 2024. Accessed November 14, 2024. https://www.parentprojectmd.org/sarepta-announces-discontinuation-of-srp-5051-development-for-duchenne/