gene research

NASHVILLE, Tennessee—Positive results from Part A of a phase 2 clinical trial called MOMENTUM, testing the safety and tolerability of the exon 51-skipping treatment SRP-5051 in Duchenne muscular dystrophy (DMD), were reported at the 2022 Muscular Dystrophy Association Clinical & Scientific Conference.

The majority of treatment-emergent events during this part of the trial were mild to moderate and included headache and nausea, according to Darko Stevanovic, MD, PhD, associate medical director and clinical development lead for RNA-targeted therapies at Sarepta Pharmaceuticals, who presented the results.

There was, however, a new safety signal of hypomagnesemia during the trial, but the analysis of all available data indicated it could be monitored and was manageable, he reported.


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Results from the trial also showed that all patients treated with 20 and 30 mg/kg of SRP-5051 experienced an increase in exon skipping and dystrophin production. Immunofluorescence analysis of muscle biopsies from patients treated with 30 mg/kg of treatment demonstrated correct localization of this dystrophin at the sarcolemma.

“If there is one message that should be taken home from this presentation, it is that MOMENTUM Part A results support further investigation of SRP-5051,” Dr. Stevanovic said.

All participants from Part A of the trial are now invited to enroll in part B, which is a dose expansion part.

SRP-5051 is an investigational phosphorodiamidate morpholino oligomer designed to skip exon 51 in the DMD gene. The aim is to restore the reading frame of the gene to allow the production of internally truncated dystrophin protein. 

Read more about exon skipping for DMD

MOMENTUM is an open-label, nonrandomized, 2-part, dose determination, and expansion study. The primary endpoints are adverse events and clinically significant laboratory abnormalities. Secondary endpoints include change from baseline at week 12 in exon skipping levels and dystrophin production, as well as pharmacokinetics. 

The trial started on June 26, 2019, and is estimated to be completed on August 31, 2024. Part 2 of the trial is currently recruiting additional participants in the US, Belgium, Canada, Spain, and the UK. 

References

Campbell C, Mathews K, van de Rijn M, et al. Phase 2 multiple-ascending-dose study of SRP-5051 PPMO in patients with DMD amenable to exon 51 skipping: Part A results. Oral presentation at: 2022 Muscular Dystrophy Association Clinical & Scientific Conference; March 16, 2022; Nashville, TN.

Two-part study for dose determination of SRP-5051 (Part A), then dose expansion (Part B) in participants with Duchenne muscular dystrophy amenable to exon 51-skipping treatment (MOMENTUM). US National Library of Medicine. Last updated February 15, 2022. Accessed March 16, 2022.