Safety and Efficacy of PF-06939926 Gene Therapy in boys with Duchenne Muscular Dystrophy: Update on data from the Phase 1b Study

Clinical Trials
77
Beth Belluscio MD, PhD, Katherine Beaverson MS, Nicolas Garnier , Kelly Ryan , Tara Moorehead , Florence Yong , Michael Binks
1. Pfizer, 2. Pfizer, 3. Pfizer, 5. Pfizer

Background: Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene that lead to severe reductions in the dystrophin protein, which is critical for the structural integrity of muscle fibers. Although muscle damage is progressive, boys <6 years old typically experience functional improvements due to ongoing development. Beginning at approximately age 6, patients decline in strength and motor skills, losing the ability to walk at 12 years, on average. PF 06939926 is a gene therapy consisting of the adeno-associated virus serotype 9 (AAV9) and mini-dystrophin gene. The ongoing, multicenter, open-label, Phase 1b study is evaluating the safety and tolerability of PF 06939926 in boys with DMD. The study also includes exploratory measures to evaluate muscle health and ambulatory function. (ClinicalTrials.gov Identifier: NCT03362502).
Methods: Ambulatory boys, aged 4–12 years, with a genetic diagnosis of DMD, and receiving a stable, daily regimen of glucocorticoids were included. Two dose levels were investigated. Primary endpoints included adverse events (AEs), abnormal laboratory results and other safety measures. Exploratory efficacy endpoints included change from baseline on the NorthStar Ambulatory Assessment (NSAA) and other measures of function.
Results: Nineteen boys received PF-06939926. The median age was 8.8 years (range, 6.2-13.0), with 12 boys (63%) aged >8.0 years. Median baseline NSAA total score was 27. Three patients had serious AEs (SAEs), previously disclosed, including one of dehydration and two relating to complement activation (acute kidney injury and thrombocytopenia); all resolved within 3 weeks. Ten boys have since been dosed with no new SAEs observed. Analysis of change from baseline in functional parameters compared with a similar cohort of external controls demonstrates improvement, unexpected for this age range.
Conclusions: PF-06939926 continues to demonstrate the potential for substantial benefit with an acceptable safety profile, and is being developed as a novel treatment to address the unmet medical need.