The U.S. Food and Drug Administration granted fast-track status for Scholar Rock’s apitegromab (Isembyld) as a treatment for facioscapulohumeral muscular dystrophy (FSHD). This status begins as participant dosing starts in the phase-2 FORGE trial.
David L. Hallal, chairman and chief executive officer at Scholar Rock, said in a statement, “We are very pleased to receive both Fast Track and Orphan Drug designations for our apitegromab FSHD program, which shows the urgency of advancing new treatment options for the FSHD community.”
Study Design
The FORGE trial is a phase 2 randomized, double-blind, placebo-controlled, multicenter study. It aims to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of apitegromab as a monotherapy in adults with genetically confirmed FSHD.
The trial will enroll approximately 60 participants randomized 1-to-1 to receive apitegromab 10 mg/kg or placebo intravenously every 4 weeks for 52 weeks. The primary end point uses percent change from baseline in total lean muscle volume (LMV) as measured by MRI at 52 weeks.
Clinical Context
FSHD is a hereditary muscular dystrophy marked by progressive and frequently asymmetric muscle weakness in the face, shoulder stabilizers, upper arms, trunk, and lower limbs. The extent of the condition and its progression rate differ significantly among individuals.
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Historically, treatment has centered on supportive and multidisciplinary care, encompassing physical and occupational therapy, exercise guidance, pain control, evaluation of respiratory function when necessary, and surgical options for certain cases.
Mechanism of Action
Apitegromab is a human monoclonal antibody that blocks myostatin activation by attaching specifically to the pro- and latent forms of myostatin found in skeletal muscle tissue. Myostatin belongs to the TGF-β family of growth factors and is mainly produced by skeletal muscle cells.
The FDA recently approved apitegromab-mstn for use in SMA patients, both adults and children aged 2 and above, who are already receiving an SMN2-targeted therapy. This approval was largely based on results from the phase 3 SAPPHIRE trial, which demonstrated a statistically significant improvement in the Hammersmith Functional Motor Scale Expanded score compared to placebo at 52 weeks.
Akshay Vaishnaw, MD, PhD, president of research and development at Scholar Rock, said, “Our preclinical data from the FlexDux4 model and prior literature suggest that, in people living with FSHD, anabolic stimuli can result in muscle hypertrophy and improved motor function. Apitegromab therefore holds important potential to impact this disease.”
