Sarepta thinks it may have a more effective DMD drug, but new side effects could be a problem

Sarepta Therapeutics says its RNA therapy for Duchenne muscular dystrophy (DMD) could be more effective than its existing drugs, but a dose-escalation study also dug up some new—and serious—adverse events.

In a trial called Momentum, Sarepta's SRP-5051 improved levels of two critical biomarkers, Sarepta said Monday, but serious side effects cropped up in three of the trial's four participants.

The latest results were another mixed bag for Sarepta's DMD program. After each bump, CEO Doug Ingram has maintained his confidence—which was the case today when he spoke to investors in an early morning call. In a previous trial mishap, Sarepta blamed a lopsided cohort when SRP-9001 failed to beat placebo.

DMD is a rare, incurable disease caused by mutations in the DMD gene that reduce production of a protein called dystrophin, leading to progressive muscle degeneration.

Drug developers have zeroed in on boosting dystrophin production in an attempt to treat the disease, which primarily affects young boys. Sarepta's therapy aims to do just that by patching portions of the gene responsible for telling the body to produce it, referred to as exon skipping. 

RELATED: Sarepta's DMD gene therapy fails phase 2 motor function test, sinking stock

Cambridge, Massachusetts-based Sarepta found evidence in the phase 2 Momentum trial that SRP-5051 increased exon skipping and boosted production of dystrophin. But the therapy, which is administered once a month, also triggered severe adverse events in several patients, according to the "safety experience" portion of a Monday company presentation.

Two patients suffered a critical drop in magnesium levels, called hypomagnesemia, and had to be treated with an IV supplement. Another patient’s potassium levels plummeted. All the patients were treated, and the cases resolved quickly, according to Sarepta. 

Because DMD is fatal and patients have few alternatives, RBC Capital Markets analysts believe the metabolic dysfunctions in the SRP-5051 Momentum trial could be managed and patients could receive preventive treatment to avoid the conditions in the first place. But regulators may take a harder look at the therapy after the side effects emerged.

RBC said regulators may also be skeptical given the small patient pool in the study, which reflected data from just four patients. Another three patients did not have biopsies done because the study was interrupted to investigate the adverse events.

Sarepta did not, however, find any instances of kidney toxicity in any of the patients, which is key, according to RBC. Pfizer, which is developing a DMD gene therapy, did report instances of kidney injury in an early-stage clinical trial, which analysts said in May 2020 could give Sarepta the edge with its DMD program. 

“Net-net, we continue to see upside potential for Sarepta,” RBC said in a note.

The efficacy data revealed in the trial are promising, even suggesting that SRP-5051 could improve on Sarepta’s three approved therapies, according to RBC. Exondys 51, Vyondys 53 and Amondys 45 all spur the same exon skipping-mechanism in particular patients.

RELATED: Pfizer's DMD gene therapy looks good in data refresh, but safety concerns persist

Sarepta said the clinical evidence suggests that exon skipping could ramp up further with longer dosing of SRP-5051. The benefits seen in the trial support continued development even with the newly identified side effects, Sarepta said in its presentation.

“The results today bolster our confidence that SRP-5051 has the potential to profoundly affect the course of disease progression in Duchenne,” said Gilmore O’Neill, M.D., vice president, R&D and chief medical officer for Sarepta.

Part A of the SRP-5051 Momentum trial is now complete, and Sarepta will move on with the pivotal Part B. The next phase will be amended to manage the hypomagnesemia risk, and the company will talk to the FDA before kicking off the study. Ingram said that the earlier trial also established that the 30 mg/kg dose will move forward.