Benzinga | May 3, 2021 08:52AM EDT

Sarepta Therapeutics Reports Clinical Results From Phase 2 MOMENTUM Study Of SRP-5051 In Patients With Duchenne Muscular Dystrophy Amenable To Skipping Exon 51; Delivered Mean Exon Skipping Of 10.79% And Mean Dystrophin Expression Of 6.55%

* Results suggest a highly potent next-generation treatment that could offer greater efficacy with less frequent dosing

* SRP-5051 dosed monthly at 30 mg/kg delivered mean exon skipping of 10.79% and mean dystrophin expression of 6.55%, consistently higher than the other SRP-5051 dosing cohorts at 12 weeks and weekly eteplirsen at 24 weeks

* Sarepta's predictive model indicates that SRP-5051 at 30 mg/kg will achieve greater than 10% dystrophin with monthly chronic dosing



Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced positive results from Part A of the MOMENTUM study (Study 5051-201), a global, Phase 2, multi-ascending dose clinical trial of SRP-5051, its next-generation peptide phosphorodiamidate morpholino oligomer (PPMO) treatment for patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping.

In biopsies taken at a median of 12 weeks and after only three doses, resultsfrom Part A of MOMENTUM study found that the 30 mg/kg of SRP-5051 dosed monthly resulted in 18 times the exon skipping and eight times the dystrophin production as eteplirsen, dosed weekly for 24 weeks. Exon-skipping and dystrophin production in the 30 mg/kg cohort were also consistently higher than the 20 mg/kg cohort of MOMENTUM. Hypomagnesemia was identified in patients taking SRP-5051. Cases have resolved with magnesium supplementation and an analysis of all available data indicate that the hypomagnesemia is monitorable and manageable.

"We are pleased to report strong, dose-dependent exon-skipping and dystrophin expression results with monthly dosing of SRP-5051 -- in ambulant and non-ambulant patients. Even at an early timepoint of 12 weeks and after as few as only three doses, these data confirm the potential of Sarepta's next-generation PPMO platform to be a step order improvement over our current PMO platform, and to profoundly impact the course of Duchenne. While we saw exceptional expression after only a few initial doses, our models predict that we will exceed dystrophin expression levels of 10% of normal or greater over time with SRP-5051," said Doug Ingram, president and chief executive officer, Sarepta. "We are excited to have chosen our target dose for further development. Part A of MOMENTUM is now complete and Sarepta will work with great urgency to discuss the results with regulatory agencies and gain their insights, including the development path to support an accelerated approval of SRP-5051 in the United States."

Results from the 30 mg/kg dose cohort:

* In biopsies taken at a median of week 12, 30 mg/kg of SRP-5051 dosed monthly resulted in mean exon skipping of 10.79% (n=4). Exon skipping was measured by digital drop polymerase chain reaction (ddPCR). This correlates to >4x increase in exon skipping compared to the 20 mg/kg cohort of SRP-5051 at 12 weeks (mean exon skipping of 2.57%, n=2) and an 18x increase in exon skipping compared to a weekly 30 mg/kg dose of eteplirsen at 24 weeks (mean exon skipping of 0.59%, n=16). At a median of week 12, 30 mg/kg of SRP-5051 resulted in mean dystrophin production of 6.55% of normal. Dystrophin expression was measured by western blot. This is twice the dystrophin expression compared to the 20 mg/kg cohort at week 12 (mean expression of 3.06%) and eight times that of the eteplirsen comparison group (mean expression of 0.82%). There were three serious, treatment-emergent adverse events in two patients in the 30 mg/kg cohort, including two cases of hypomagnesemia. The events were asymptomatic and have resolved with magnesium supplementation. Markers of kidney function have generally been normal and not shown any consistent relationship to the hypomagnesemia. Predictive modeling for dystrophin accumulation that includes assumptions of known turnover of dystrophin in the muscle and an analysis of data generated with the PPMO platform indicates that SRP-5051 at 30 mg/kg is likely to deliver greater than 10% dystrophin over time with monthly dosing. Full results will be presented at a future medical meeting. About MOMENTUM (Study SRP-5051-201) MOMENTUM is a multi-arm, ascending dose study designed to identify the maximum tolerated dose of SRP-5051, infused monthly. The study will enroll up to 24 patients, both ambulant and non-ambulant, between the ages of 7 to 21 at sites in the U.S., Canada, Australia and European Union. The primary endpoint is safety, and secondary and exploratory endpoints include exon-skipping, dystrophin expression and tissue concentration. More information can be found on www.clinicaltrials.gov.