LB: Fordadistrogene movaparvovec for Duchenne muscular dystrophy: 3-year functional outcomes and changes in thigh and upper-limb muscle volume


Clinical Trials

Poster Number: T431


Perry Shieh, MD, PhD, UCLA, Russell Butterfield, MD PhD, University of Utah, Francesco Muntoni, MD, Great Ormond Street Institute of Child Health, Eugenio Mercuri, MD PhD, Catholic University of the Sacred Heart, James Signorovitch, PhD, Analysis Group, Sarah Sherlock, PhD, Pfizer, Huihua Li, PhD, Pfizer, Heliang Shi, PhD, Pfizer, Codrin Lungu, MD, Pfizer, Inc., Kelly Ryan, RN, MS, Pfizer, Qi Shen, MD, PhD, Pfizer, Inc., Edward Smith, MD, Duke

Background: Fordadistrogene movaparvovec (FM), an AAV9 gene-replacement construct containing a mini-dystrophin transgene, is being evaluated in an ongoing phase 1b study. Here, we present changes in motor function at 3 years (y) vs an external control group, and assess changes in thigh and upper-limb muscle volume and their relationship with changes in motor function.
Methods: Ambulatory participants (N=16) with a confirmed diagnosis of Duchenne muscular dystrophy (DMD) received a single infusion of FM (2E14 vg/kg). Change from baseline (CFB) in North Star Ambulatory Assessment (NSAA) was reported at 3y. A prediction model developed within the cTAP collaboration using large natural history databases was used to generate an external control group for contextualization of NSAA results. Muscle volume was evaluated using magnetic resonance imaging.
Results: At baseline, mean (standard deviation [SD]) age in the clinical trial group was 8.5 (1.7) y and NSAA total score was 25.8 (4.6). Prior to enrollment, 50% of participants were using daily deflazacort and 50% daily prednisone/prednisolone. Mean (SD) NSAA total score was 27.3 (4.1) in participants aged 6 to <8y (n=6) and 24.8 (4.8) in those aged ≥8 to 12y (n=10). At 3y, mean (standard error [SE]) CFB in NSAA overall was -6.4 (2.0) in the FM group vs -7.8 (0.6) in the cTAP group (difference of +1.4 [95% CI: -2.8, 5.5]). In those aged 6 to <8y and ≥8 to 12y, FM was associated with a difference of +3.8 (95% CI: 2.1, 5.6) and -0.1 (95% CI: -5.4, 5.2), respectively. At 3y, the mean (SD) %CFB in thigh muscle volume in the overall population was 4.1% (17.0), and 23.6% (18.8) in upper-limb muscle volume. Correlation between CFB in NSAA and %CFB in thigh muscle volume in the overall population was moderately strong (Spearman correlation=0.60). Participants with CFB in NSAA ≥0 had mean (SD) %CFB in thigh muscle volume of 13.5% (14.4) vs -0.1% (17.1) in participants with CFB in NSAA <0. Additional relationships between muscle volume changes and physical function will be presented. At 3y no new safety signals of concern were observed vs 2y follow-up.
Conclusions: At 3y, a clinically meaningful preservation of motor function was observed in participants with DMD aged 6 to <8y receiving FM vs an external control. Sustained increases in upper-limb muscle volume were observed. CFB in NSAA was moderately strongly correlated with %CFB in thigh muscle volume. This study was sponsored by Pfizer. NCT0336250