Sarepta May Have a Smooth Road to DMD Gene Therapy Approval


Competitors REGENXBIO and Capricor Therapeutics both have gene therapy candidates in clinical trials.

Sarepta’s road to approval for treating Duchenne muscular dystrophy (DMD) with its gene therapy delandistrogenemoxeparvovec (SRP-9001) may be smoothed out after the company revealed that the FDA would not be requiring an advisory committee meeting prior to the PDUFA date of May 29, 2023.1

“2023 may be the most event eventful year in Sarepta’s event-filled history,” Doug Ingram, president and chief executive officer, Sarepta, said in a recent earnings call.1 “They confirmed they saw no significant safety issues with the program to be able to identify any significant clinical issues or major deficiencies and then determined that they didn't need an AdComm. That's where we are right now.”

Sarepta submitted the biologics license application for the therapy in September 2022. The therapy yielded clinical improvements and biomarker expression in over 80 treated patients with DMD so far in the phase 1/2 Study SRP-9001-101 (NCT03375164), the phase 2 SRP-9001-102 study (NCT03769116), and the phase 1 ENDEAVOR study (SRP-9001-103; NCT04626674) and is now being evaluated in the phase 3 EMBARK study.

Most recently, data from the ENDEAVOR study as of July 2022 showed with follow-up of up to 4 years post-treatment, participants treated with the adeno-associated virus (AAV) therapy demonstrated an improvement of 4 points on the North Star Ambulatory Assessment (NSAA) from pre-therapy baselines in 20 participants at 52 weeks, as well as a 3.8-point (unadjusted means) and 3.2-point (least squared means) improvement compared to a propensity-weighted external control group (<.0001).2

READ MORE: Upcoming FDA Decisions for Rare Diseases in 2023

Longer follow-up data from 4 patients from Study SRP-9001-101 showed a 7-point improvement above pre-treatment baselines on the NSAA, a 9.9-point unadjusted means and a 9.4-point least squared means versus a propensity-weighted external control (= .0125) at 4 years. An integrated analysis of 52 patients across studies SRP-9001-101, SRP-9001-102 (NCT03769116), and ENDEAVOR also showed that at 1 year, patients treated with SRP-9001 at the target dose improved 3.1 points (unadjusted means) and 2.4 points (least squared means) on NSAA versus propensity-weighted external control (<.0001).

“Every hour of every day, this ruthless disease, Duchenne, robs thousands of children in the United States of muscle as it steals their future from them. Sarepta’s BLA submission for an accelerated approval of SRP-9001 is a significant milestone in our quest to intervene with urgency on behalf of the children we serve,” Ingram said in a previous statement.“If approved, SRP-9001 will be the first gene therapy available for Duchenne patients. We are enormously grateful to the courageous families who have participated in the SRP-9001 trials and to the participating clinical investigators and experts who have guided us and played a crucial part in reaching this milestone.”

Trailing behind Sarepta are Capricor Therapeutics’ CAP-1002, an investigational allogeneic cardiosphere-derived cell therapy, and RGX-202, REGENXBIO’s investigational AAV gene therapy, which are both in clinical trials for treating DMD. CAP-1002 recently demonstrated long-term improvements from the HOPE-2 study (NCT03406780) open-label extension in Performance of the Upper Limb, cardiac MRI assessments, and left ventricular ejection fraction (LVEF) findings.4 Meanwhile, REGENXBIO began recruiting patients with DMD in the phase 1/2 AFFINITY DUCHENNE clinical trial (NCT05693142) in January 2023.5

1. Sarepta Therapeutics fourth quarter and full-year 2022 earnings call. News release. Sarepta Therapeutics. February 28, 2023.
2. Sarepta Therapeutics’ investigational gene therapy SRP-9001 for Duchenne muscular dystrophy demonstrates significant functional improvements across multiple studies. News release. Sarepta Therapeutics, Inc. July 6, 2022.
3. Sarepta Therapeutics submits biologics license application for SRP-9001 for the treatment of ambulant patients with Duchenne muscular dystrophy. News release. Sarepta Therapeutics. Septemebr 29, 2022.
4.Capricor Therapeutics announces positive 18-month results from ongoing HOPE-2 open label extension study of CAP-1002 in Duchenne muscular dystrophy patients. News release. Capricor Therapeutics. January 25, 2023. Accessed January 25, 2023.
5. REGENXBIO announces phase I/II trial of RGX-202, a novel gene therapy candidate for Duchenne muscular dystrophy, is active and recruiting patients. News release. REGENXBIO Inc. January 23, 2023.
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