2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Long-term safety and sustained functional benefit in patients with DMD 4 years post-treatment with delandistrogene moxeparvovec: a Phase 1/2a study

Pdf Summary

The study evaluated the long-term safety and functional benefit of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy (DMD). The results showed that a single intravenous administration of delandistrogene moxeparvovec was well tolerated, with no new safety concerns identified. Any treatment-related adverse events occurred within the first 70 days post-infusion and resolved. Functional assessments demonstrated sustained improvement in motor function, even at ages when functional decline is expected in DMD. This suggests long-term expression of the dystrophin protein in target muscles.<br /><br />Delandistrogene moxeparvovec is a gene therapy that aims to compensate for the missing dystrophin protein in DMD by delivering a transgene encoding a modified dystrophin protein called SRP-9001. The primary outcome measure of the study was safety based on the occurrence of adverse events. Additional outcome measures included dystrophin expression in muscle biopsies and changes in motor function as assessed by the North Star Ambulatory Assessment (NSAA) and timed function tests.<br /><br />The study included four patients with DMD, and the data showed that delandistrogene moxeparvovec treatment led to sustained functional improvement over the 4-year follow-up period. The patients showed a mean increase of 7 points in the NSAA total score from baseline to year 4. Additionally, timed function tests, such as time to rise and 100-meter walk/run, also showed improvements.<br /><br />A post hoc analysis compared the 4-year data from Study 101 with data from a propensity-score-weighted external control cohort. The analysis further supported the efficacy of delandistrogene moxeparvovec, with a mean change in NSAA total score of 9.4 points favoring the treated patients compared to the external control cohort.<br /><br />Overall, the study demonstrated that delandistrogene moxeparvovec gene therapy is safe and leads to sustained functional improvement in patients with DMD. These findings provide promising insights into the potential benefits of this therapy for the DMD community.

Asset Subtitle

Submitter Only - Megan Speakman, MA; Presenting Author - Erin O’Rourke, MS, CGC; Co-Author - Jerry R. Mendell, MD; Co-Author - Zarife Sahenk, MD, PhD; Co-Author - Kelly J. Lehman, MSN, CNP; Co-Author - Linda P. Lowes, PT, PhD; Co-Author - Natalie F. Reash, PT, DPT; Co-Author - Megan A. Iammarino, PT, DPT; Co-Author - Lindsay N. Alfano, DPT, PCS; Co-Author - Sarah Lewis, PhD; Co-Author - Kathleen Church, MSW; Co-Author - Richard Shell, MD; Co-Author - Rachael A. Potter, PhD; Co-Author - Danielle A. Griffin, MS; Co-Author - Mark J Hogan, MD; Co-Author - Shufang Wang, PhD; Co-Author - Stefanie Mason, MD, MPH; Co-Author - Eddie Darton, MD, JD; Co-Author - Louise R. Rodino-Klapac, PhD;

Meta Tag

Musculoskeletal system

Therapy

Co-Author Jerry R. Mendell, MD

Co-Author Zarife Sahenk, MD, PhD

Co-Author Kelly J. Lehman, MSN, CNP

Co-Author Linda P. Lowes, PT, PhD

Co-Author Natalie F. Reash, PT, DPT

Co-Author Megan A. Iammarino, PT, DPT

Co-Author Lindsay N. Alfano, DPT, PCS

Co-Author Sarah Lewis, PhD

Co-Author Kathleen Church, MSW

Co-Author Richard Shell, MD

Co-Author Rachael A. Potter, PhD

Co-Author Danielle A. Griffin, MS

Co-Author Mark J Hogan, MD

Co-Author Shufang Wang, PhD

Co-Author Stefanie Mason, MD, MPH

Co-Author Eddie Darton, MD, JD

Co-Author Louise R. Rodino-Klapac, PhD

Presenting Author Erin O’Rourke, MS, CGC

Submitter Only Megan Speakman, MA

Keywords

delandistrogene moxeparvovec

gene therapy

Duchenne muscular dystrophy

long-term safety

functional benefit

motor function

dystrophin protein

SRP-9001

North Star Ambulatory Assessment

timed function tests