E - Disease Models and Clinical Applications -> Musculo-skeletal Diseases
Two-Year Clinical Outcomes with Fordadistrogene Movaparvovec for Duchenne Muscular Dystrophy (DMD) and Contextualization with External Controls
Type: Oral Abstract Session
Presentation Details
Session Title: Late-Breaking Abstracts 1
Location: Room 515 AB
Start Time: 5/19/2023 8:00
End Time: 5/19/2023 8:15
Background: The safety and efficacy of fordadistrogene movaparvovec (PF-06939926), an adeno-associated virus serotype-9 gene-replacement construct containing a mini-dystrophin transgene, is being assessed for DMD in an ongoing phase 1b trial (NCT03362502). Here, we report the effect of fordadistrogene movaparvovec on motor function at 2 years compared with selected external control groups. Methods: Ambulatory subjects (n=16) with confirmed genetic diagnosis of DMD received a single intravenous dose (2E14 vg/kg) of fordadistrogene movaparvovec. An external control group was generated from a prediction model developed within the cTAP collaboration using large natural history databases, with adjustments for baseline age, steroid use, and ambulatory function profile. A second external control group with similar baseline characteristics was constructed using 2-year data from patients with at least 1 year of treatment randomized to active→placebo, placebo→active, or active→active in a null phase 3 domagrozumab trial. For the second control group, propensity score adjustment was applied to reduce group selection bias and control for known confounding variables. The North Star Ambulatory Assessment (NSAA) was used to assess ambulatory function before and after treatment and compared with the external control groups. Results: At baseline, the mean (standard deviation [SD]) NSAA total score was 25.8 (4.6), and scores were 27.3 (4.1) and 24.8 (4.8) in those aged 6-7 years (n=6) and 8-12 years (n=10), respectively. At 2 years, the mean (standard error [SE]) change from baseline was -2.6 (1.5) with fordadistrogene movaparvovec versus -4.9 (0.5) from the cTAP model (preservation of +2.4; 95% CI [-0.6, 5.4]). For those aged 6-7 years, mean (SE) change at 2 years was +0.5 (1.0) with fordadistrogene movaparvovec versus -2.0 (0.5) from the cTAP model (preservation of +2.5; 95% CI [0.4, 4.7]). For those aged 8-12 years, mean (SE) change was -4.4 (2.1) with fordadistrogene movaparvovec versus -6.7 (0.6) from the cTAP model (preservation of +2.3; 95% CI [-2.0, 6.5]). In the second external control group, the mean (SE) change at 2 years was -3.6 (1.3) (preservation of +4.1; 95% CI [1.0, 7.2]) for those aged 6-7 years, and -4.0 (0.9) (difference of -0.4; 95% CI [-5.2, 3.4]) for those aged 8-12 years. Conclusions: At 2 years, fordadistrogene movaparvovec was associated with clinically meaningful preservation of motor function in subjects with DMD when compared with selected external controls with similar pre-treatment characteristics. As this was a comparison with non-randomized groups or pooled clinical trial data there is the potential for confounding bias. Continued assessment of fordadistrogene movaparvovec is warranted in randomized, placebo-controlled trials. This study was sponsored by Pfizer.
Perry B. Shieh1, Russell J. Butterfield2, Francesco Muntoni3, Eugenio Mercuri4, James Signorovitch5, Pamela F. Schwartz6, Huihua Li6, Michael Binks6, Tara McDonnell6, Kelly Ryan6, Marielle Delnomdedieu6, Qi Shen6, Daniel I. Levy6, Edward C. Smith7
1UCLA, Los Angeles, CA,2University of Utah School of Medicine, Salt Lake City, UT,3Great Ormond Street Institute of Child Health, UCL, London, United Kingdom,4Catholic University, Rome, Italy,5Analysis Group, Boston, MA,6Pfizer Inc, New York, NY,7Duke University School of Medicine, Durham, NC
P.B. Shieh: 1; Commercial Interest i.e. Company X; Alexion. 1; What was received? i.e. Honorarium; Consulting fee. 1; For what role? i.e. Speaker; Consultancy. 2; Commercial Interest i.e. Company X; AveXis. 2; What was received? i.e. Honorarium; Consulting fee. 2; For what role? i.e. Speaker; Consultancy. 3; Commercial Interest i.e. Company X; Biogen. 3; What was received? i.e. Honorarium; Consulting fee. 3; For what role? i.e. Speaker; Consultancy. 4; Commercial Interest i.e. Company X; Catalyst. 4; What was received? i.e. Honorarium; Consulting fee. 4; For what role? i.e. Speaker; Consultancy. 5; Commercial Interest i.e. Company X; CSL Behring. 5; What was received? i.e. Honorarium; Consulting fee. 5; For what role? i.e. Speaker; Consultancy. 6; Commercial Interest i.e. Company X; Genentech. 6; What was received? i.e. Honorarium; Consulting fee. 6; For what role? i.e. Speaker; Consultancy. 7; Commercial Interest i.e. Company X; Grifols. 7; What was received? i.e. Honorarium; Consulting fee. 7; For what role? i.e. Speaker; Consultancy. 8; Commercial Interest i.e. Company X; Pfizer. 8; What was received? i.e. Honorarium; Consulting fee. 8; For what role? i.e. Speaker; Consultancy. 9; Commercial Interest i.e. Company X; PTC Therapeutics. 9; What was received? i.e. Honorarium; Consulting fee. 9; For what role? i.e. Speaker; Consultancy. 10; Commercial Interest i.e. Company X; Sarepta Therapeutics. 10; What was received? i.e. Honorarium; Consulting fee. 10; For what role? i.e. Speaker; Consultancy.
Find This Presentation