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A - Viral Vector Development -> AAV Vectors – Clinical Studies

Results of One Year Follow-Up After Treatment With Fordadistrogene Movaparvovec (PF-06939926) for Duchenne Muscular Dystrophy (DMD) in A Phase 1b, Open-label Study

Type: Oral Abstract Session

Presentation Details
Session Title: Late-Breaking Abstracts II
Location: Ballroom C
Start Time: 5/18/2022 8:00
End Time: 5/18/2022 8:15

Background: Fordadistrogene movaparvovec (PF-06939926) is an adeno-associated virus serotype-9 (AAV9) gene-replacement construct containing a truncated dystrophin transgene (mini-dystrophin), which aims to restore functional protein to cardiac and skeletal muscle. We present 1 year data from ambulatory participants in a phase 1b, multicenter, single-arm, open-label trial (NCT03362502). Methods: Ambulatory boys with a genetic diagnosis of DMD and receiving a stable, daily glucocorticoid regimen were eligible. Fordadistrogene movaparvovec was administered as a single intravenous infusion, at low- or high-dose. Mini-dystrophin expression and distribution in biceps biopsies were analyzed by liquid chromatography-mass spectrometry (LCMS) and immunofluorescence (IF), respectively. Functional endpoints included change from baseline in the North Star Ambulatory Assessment (NSAA) and other measures of motor and respiratory function. Results: Nineteen ambulatory boys received fordadistrogene movaparvovec (n=3 low-dose; n=16 high-dose). Median age at gene therapy infusion was 8.8 yrs (range: 6.2-13.0 yrs); median baseline NSAA total score was 27 (range 17-32). Three treatment-related serious adverse events occurred (dehydration, acute kidney injury, thrombocytopenia) as previously reported; all resolved within 15 days. For participants in the high-dose group, mean dystrophin/mini-dystrophin levels were 22% and 40% of normal at 2 and 12 months, respectively (measured via LCMS). Dystrophin-positive fibers were 39% and 62% at 2 and 12 months, respectively (measured via IF). A consistent trend towards improved function was seen at 1-year following treatment with fordadistrogene movaparvovec compared with the decline observed in the external control cohort (placebo trial participants of similar age, weight, baseline function, stable steroid use) (Table). Conclusion: Preliminary results indicate that fordadistrogene movaparvovec has an acceptable safety profile in this population, provides for substantial expression of mini-dystrophin that increases (on average) between 2 and 12 months, and has the potential to benefit ambulatory DMD patients across a range of functions.



Russell J. Butterfield1, Perry B. Shieh2, Florence Yong3, Michael Binks3, Tara G. McDonnell3, Kelly A. Ryan3, Marielle Delnomdedieu3, Beth A. Belluscio3, Srividya Neelakantan3, Daniel I. Levy3, Pamela F. Schwartz3, Edward C. Smith4

1University of Utah School of Medicine, Salt Lake City, UT,2University of California at Los Angeles (UCLA), Los Angeles, CA,3Pfizer Inc, New York, NY,4Duke University School of Medicine, Durham, NC
  R.J. Butterfield: 1; For what role? i.e. Speaker; received support from, and/or has served as a paid consultant for, AavantiBio, AveXis, Capricor Therapeutics, Catabasis, PTC Therapeutics, Sarepta Therapeutics, Pfizer, Biogen, Scholar Rock, and Accel.

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