A Phase 1b/2 Study of the Anti-Myostatin Adnectin RG6206 (BMS-986089) in Ambulatory Boys with Duchenne Muscular Dystrophy: A 72-Week Treatment Update (P1.6-062)

Objective: To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of the anti-myostatin adnectin RG6206 (BMS-986089) in a Phase 1b/2 study (NCT02515669) in ambulatory boys with Duchenne muscular dystrophy (DMD). Background: Pharmacologic inhibition of myostatin, a negative regulator of muscle growth, has been shown to increase skeletal muscle mass in several species, including humans. Design/Methods: Forty-three ambulatory boys with DMD, aged 5–10 years, were randomized to receive weekly subcutaneous injections of RG6206 (4–50 mg) or placebo during a 24-week double-blind phase (treatment: placebo ratio 3:1). All participants then received RG6206 throughout a 48-week open-label phase. The primary endpoint of this study was safety and tolerability over 24 weeks. Secondary endpoints included the PK of RG6206, frequency and titer of anti-drug antibodies (ADAs), and effect on serum myostatin levels. Exploratory outcomes included timed function tests and dual-energy X-ray absorptiometry imaging of lean body mass (LBM). Results: At 24 weeks’ treatment, the most common adverse events were mild-to-moderate injection site reactions, which resolved without change to study treatment. No clinically significant changes in laboratory values, vital signs, electrocardiogram parameters or echocardiogram were observed. One patient had a positive ADA titer at a single time point; this was not accompanied by hypersensitivity or injection site reactions. RG6206 treatment resulted in a dose-dependent reduction (77–97%) in free myostatin. We will report on the effect of treatment on LBM index in boys with DMD who received RG6206 for 72 weeks compared with boys with DMD in the Collaborative Trajectory Analysis Project who had not received any treatment. Conclusions: No drug-related safety findings leading to withdrawal from the study were identified. In total, 41 patients from this study are now enrolled in a 228-week open-label extension. A Phase 2/3 RG6206 study is actively recruiting (NCT03039686). Disclosure: Dr. Wagner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sarepta, Wave, Fibrogen, Dynacure, Lion, and PTC Therapeutics. Dr. Wagner has received research support from Pfizer, Roche, and Sarepta. Dr. Wong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Wave Life Sciences, and AveXis. Dr. Byrne has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Inc.. Dr. Byrne has received compensation for serving on the Board of Directors of Applied Genetic Technologies Corporation (AGTC). Dr. Byrne has received royalty, license fees, or contractual rights payments from University of Florida. Dr. Tian has received research support from Pfizer, BMS, Roche, Fibrogen, PTC, Sarepta. Dr. Jacobsen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Shire. Dr. Jacobsen holds stock and/or stock options in Shire which sponsored research in which Dr. Jacobsen was involved as an investigator. Dr. Jacobsen holds stock and/or stock options in Shire. Dr. Jacobsen has received research support from Shire. Dr. Tirucherai has nothing to disclose. Dr. Rabbia has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche/Genentech. . Dr. Kletzl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche. Dr. Kletzl holds stock and/or stock options in F. Hoffmann-La Roche which sponsored research in which Dr. Kletzl was involved as an investigator. Dr. Kletzl holds stock and/or stock options in F. Hoffmann-La Roche. Dr. Kletzl has received research support from F. Hoffmann-La Roche. Dr. Dukart has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche. Dr. Dukart holds stock and/or stock options in F. Hoffmann-La Roche which sponsored research in which Dr. Dukart was involved as an investigator. Dr. Ong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche. Dr. Ong holds stock and/or stock options in F. Hoffmann-La Roche. Dr. Yen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann La-Roche. Dr. Sajeev has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Analysis Group, Inc. and Collaborative Trajectory Analysis Project (cTAP). Dr. Signorovitch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Analysis Group Inc. Dr. Ward has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with The Analysis Group Inc. Dr. Bechtold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bristol-Myers Squibb. Dr. Bechtold holds stock and/or stock options in Bristol-Myers Squibb, which sponsored research in which Dr. Bechtold was involved as an investigator. Dr. Krishnan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche and Biogen.