Positive Phase 2 Data for SRP-5051 in Duchenne Muscular Dystrophy

Positive phase 2 data on SRP-5051 (vesleteplirsen; Sarepta Therapeutics) for use among ambulatory and nonambulatory male patients who have Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping show the treatment’s effectiveness at its lower and higher determined doses, according to a press release from Sarepta Therapeutics.¹

Efficacy of the next-generation peptide phosphorodiamidate morpholino oligomer is currently being investigated in part B of the global, multi-ascending-dose Momentum trial.² Part A evaluated SRP-5051 to determine its maximum tolerated dose, with the low and high doses being approximately 20 mg/kg and 30 mg/kg, both administered every 4 weeks.

A young boy in his wheelchair

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To qualify for trial enrollment, patients had to be male, aged 7 to 21 years, and treatment naïve; have a genetic diagnosis of DMD amenable to exon 51 skipping treatment; have a 12-week history of continuous stable corticosteroid dosing or not have received any corticosteroids for at least 12 weeks prior to SRP-5051 administration; not have received any exon-51 skipping treatment in the 4 weeks leading up to their Momentum screening or any gene therapy for DMD; and not have a diagnosis of hypomagnesemia, serum creatinine above the upper limit of normal, or abnormal electrolyte values at screening.³

For those in the 30 mg/kg dose cohort (n = 20), SRP-5051 produced these results:

• 5.17% mean dystrophin expression
• 4.53% mean change from baseline
• 11.11% mean exon skipping, for a 10.07% improvement from baseline

For those in the 20 mg/kg dose cohort (n = 20), SRP-5051 produced these results:

• 2.81% mean dystrophin expression
• 1.60% mean change from baseline
• 2.47% mean exon skipping, for a 2.00% improvement from baseline

Compared with a weekly 30 mg/kg dose of eteplirsen at 24 weeks, the positive changes in dystrophin expression and exon skipping seen with the 30 mg/kg dose of SRP-5051 symbolize 12.2- and 24.6-fold increases, respectively, and the improvements at the 20-mg/kg dose, 4.3- and 4.9-fold increases.

“The dystrophin production delivered by SRP-5051 in the Momentum study is very encouraging. Importantly, with effective supplementation and monitoring, we have not seen additional complications from the hypomagnesemia,” said Eugenio Mercuri, MD, PhD, head of the Neuromuscular Unit, Catholic University, Rome, Italy, and an investigator in the study, in the statement from Sarepta. “The results with SRP-5051 to date suggest it could play an important role in the treatment of Duchenne patients with a confirmed exon 51 amenable mutation.”

Hypomagnesemia, or magnesium deficiency, is 1 of 2 serious treatment-emergent adverse events seen in part B of the Momentum trial; there were 4 cases in addition to the 3 instances of hypokalemia, or lower-than-normal potassium in the blood.

Overall, these newest data from Momentum part b support a favorable benefit-risk profile for SRP-5051.

SRP-5051 is also currently being investigated in an open-label extension study.⁴

References

1. Sarepta Therapeutics announces positive data from part B of MOMENTUM, a phase 2 study of SRP-5051 in patients with Duchenne Muscular dystrophy amenable to skipping exon 51. News release. Sarepta Therapeutics. January 29, 2024. Accessed February 13, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-positive-data-part-b-momentum?_ga=2.113508740.2041392848.1707850235-1441231226.1700256311
2. Two-part study for dose determination of vesleteplirsen (SRP-5051) (part A), then dose efficacy (Part B) in participants with Duchenne Muscular dystrophy amenable to exon 51-skipping treatment (MOMENTUM). ClinicalTrials.gov. Updated December 1, 2023. Accessed February 13, 2024. https://clinicaltrials.gov/study/NCT04004065
3. Momentum (5051-201). Sarepta Therapeutics. Accessed February 13, 2024. https://clinicaltrials.sarepta.com/momentumtrial
4. An open-label extension study for patients with Duchenne muscular dystrophy who participated in studies of SRP-5051 (vesleteplirsen). ClinicalTrials.gov. Updated September 28, 2023. Accessed February 13, 2024. https://clinicaltrials.gov/study/NCT03675126