Abstract Details

Title Phase 1/2a Trial of SRP-9001 in Patients with Duchenne Muscular Dystrophy: 3-Year Safety and Functional Outcomes

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S23 - Therapeutics for Muscle Diseases (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Background

The investigational gene transfer therapy SRP-9001 is being developed to achieve targeted skeletal and cardiac muscle expression of a shortened functional micro-dystrophin protein.

Objective

This Phase 1/2a, single-dose, open-label clinical trial (NCT03375164) evaluates the safety of systemic gene transfer of rAAVrh74.MHCK7.micro-dystrophin (SRP-9001) in patients with Duchenne muscular dystrophy (DMD).

Design/Methods

Four ambulatory patients with DMD (4–7 years old) were enrolled. Patients were given an intravenous infusion of SRP-9001 at a dose of 2.0x10¹⁴ vg/kg (supercoiled qPCR, linear plasmid standard equivalent of 1.33x10¹⁴ vg/kg) and prednisone (1 mg/kg/day) 1 day pre- to 30 days post-gene delivery. The primary outcome measure is safety. The secondary outcome measures include micro-dystrophin expression quantified by immunofluorescence and western blot in pre- and post-muscle biopsy (Week 12 post-infusion). Key efficacy outcome measures include change in the North Star Ambulatory Assessment (NSAA) and timed function tests (100m, 4-Stair Climb, and Time to Rise).

Results

Three-year data demonstrated that SRP-9001 was linked to an acceptable safety profile. Treatment-related adverse events (AEs) were mild to moderate, occurred mostly in the first 90 days of treatment, and all resolved. No serious AEs, study discontinuations, or AEs associated with clinical complement activation were reported. All patients demonstrated a clinically meaningful improvement on NSAA (mean change [standard deviation] from baseline to Year 3: +7.5 points [3.42]). Patients treated with SRP-9001 generally maintained muscle strength (Time to Rise and 4-Stair Climb) and showed improvement in ambulation ability (100m) from baseline to Year 3.

Conclusions

The observed safety profile and the enduring response following gene transfer provides proof-of-concept for the continuation of clinical trials assessing SRP-9001 using single-dose gene transfer therapy in patients with DMD. We present the latest long-term (3-year) safety and functional data from this study.

This study was funded by Sarepta Therapeutics, Inc.

Authors/Disclosures
Jerry R. Mendell, MD, FAAN (The Research Institute at Nationwide Children's Hospital) PRESENTER	Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics . The institution of Dr. Mendell has received research support from Sarepta.
Zarife Sahenk, MD, PhD, FAAN (The Research Institute at Nationwide Childrens.org)	Dr. Sahenk has nothing to disclose.
Kelly Lehman, MSN, CNP (Nationwide Children's Hospital- The Research Institute)	Ms. Lehman has nothing to disclose.
	No disclosure on file
Linda P. Lowes, PT PhD	The institution of Ms. Lowes has received research support from Sarepta Therapeutics.
Natalie Reash (Nationwide Children's Hospital)	No disclosure on file
Megan Iammarino, PT (Nationwide Children'S Hospital)	Dr. Iammarino has nothing to disclose.
Lindsay N. Alfano, PT (Nationwide Children'S Hospital)	Ms. Alfano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ATOM International, Ltd (Amicus Therapeutics, Catabasis, Genethon, Italfarmaco, NS Pharma, Pfizer, PTC Therapeutics). Ms. Alfano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta Therapeutics. The institution of Ms. Alfano has received research support from Novartis Gene Therapies. The institution of Ms. Alfano has received research support from Sarepta Therapeutics. The institution of Ms. Alfano has received research support from Audentes Therapeutics/Astellas Gene Therapies. Ms. Alfano has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Sarah E. Lewis (Sarepta Therapeutics)	Mrs. Lewis has received personal compensation for serving as an employee of Sarepta Therapeutics . Mrs. Lewis has stock in Sarepta Therapeutics.
Kathleen Church	No disclosure on file
Richard Shell	No disclosure on file
Rachael Potter	No disclosure on file
Danielle A. Griffin	Ms. Griffin has stock in Sarepta Therapeutics. Ms. Griffin has received intellectual property interests from a discovery or technology relating to health care.
Eric Pozsgai	Eric Pozsgai has received personal compensation for serving as an employee of Sarepta Therapeutics. Eric Pozsgai has received stock or an ownership interest from Sarepta Therapeutics.
Mark Hogan (Nationwide Children’s Hospital)	No disclosure on file
	No disclosure on file
Kathryn A. Giblin, MD	Dr. Giblin has received personal compensation for serving as an employee of Sarepta Therapeutics. Dr. Giblin has received stock or an ownership interest from Sarepta Therapeutics. Dr. Giblin has received intellectual property interests from a discovery or technology relating to health care.
Louise R. Rodino-Klapac (Sarepta Therapeutics)	Ms. Rodino-Klapac has received personal compensation for serving as an employee of Sarepta Therapeutics, Inc.. Ms. Rodino-Klapac has received stock or an ownership interest from Sarepta Therapeutics. Ms. Rodino-Klapac has received intellectual property interests from a discovery or technology relating to health care.