Apitegromab Gains FDA Fast Track Designation for FSHD as Phase 2 FORGE Trial Starts

The FDA has granted fast track designation to Scholar Rock’s apitegromab (Isembyld), a muscle-targeting therapy recently approved for the treatment of spinal muscular atrophy (SMA), for patients living with facioscapulohumeral muscular dystrophy (FSHD), coinciding with the start of participant dosing in the phase 2 FORGE trial (NCT07435129).¹

“We are very pleased to receive both Fast Track and Orphan Drug designations for our apitegromab FSHD program, which underscores the urgency of advancing new treatment options for the FSHD community,” David L. Hallal, chairman and chief executive officer at Scholar Rock, said in a statement.¹ “With participant dosing now underway in our Phase 2 FORGE study, we are one step closer to realizing the broader potential of our world-leading myostatin platform and bringing a potentially transformative muscle-targeted therapy to people living with FSHD worldwide.”

Study Design

FORGE is a phase 2 andomized, double-blind, placebo-controlled, multicenter study aiming to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of apitegromab as a monotherapy in adults with genetically confirmed FSHD. The trial, presented at the 2026 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 9-11, in Orlando, Florida, will enroll approximately 60 participants randomized 1-to-1 to receive apitegromab 10 mg/kg or placebo intravenously every 4 weeks for 52 weeks.²

In the phase 2 study, the primary end point is percent change from baseline in total lean muscle volume (LMV) as measured by MRI at 52 weeks. Secondary end points include percent change from baseline in total LMV at Week 24, change from baseline in additional muscle parameters such as muscle fat fraction at 24 weeks and 52 weeks, and safety and tolerability. The company noted that additional exploratory end points will also be assessed.

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The FSHD program is supported by translational preclinical data, which showed that a murine form of apitegromab increased muscle mass, strength, and endurance in mouse models. “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,” Akshay Vaishnaw, MD, PhD, president of eesearch and development at Scholar Rock, said in a statement.¹

“We believe FORGE, which assesses changes in lean muscle volume as well as a range of exploratory functional endpoints, will enable robust evaluation of apitegromab and inform on the drug’s potential to drive meaningful functional outcomes,” Vaishnaw added in a statement.¹

Clinical Context

FSHD is an inherited muscular dystrophy characterized by progressive and often asymmetric weakness affecting the facial, scapular stabilizer, upper-arm, truncal, and lower-extremity muscles. Clinical severity and the rate of progression vary substantially among affected individuals. Some patients develop marked limitations in upper-extremity function or ambulation, whereas others retain comparatively mild function over long periods.³

Management has historically emphasized supportive and multidisciplinary care, including physical and occupational therapy, exercise counseling, pain management, assessment of respiratory involvement when clinically indicated, and orthopedic interventions for selected patients.³ This variability in phenotype and progression complicates therapeutic trial design because detectable changes in function may occur slowly and differ across muscle groups.

Mechanism of Action

Apitegromab is a human monoclonal antibody that inhibits myostatin activation by selectively binding to the pro- and latent forms of myostatin in skeletal muscle. Myostatin, a member of the TGF-β superfamily of growth factors, is produced primarily by skeletal muscle cells. Across multiple species, including humans, absence of the myostatin gene has been linked to increased muscle mass and strength.

Recently, the FDA approved apitegromab-mstn for SMA in adults and pediatric patients 2 years and older who currently receive an SMN2-targeted treatment, becoming the first FDA-approved SMA therapy designed to directly target muscle loss.⁴ The decision was supported primarily supported by data from the phase 3 SAPPHIRE study (NCT05156320), showing that treatment with the apitegromab resulted in a statistically significant difference in change from baseline on the Hammersmith Functional Motor Scale Expanded compared with placebo at 52 weeks.⁵

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REFERENCES
1. Scholar Rock receives FDA Fast Track designation for apitegromab facioscapulohumeral muscular dystrophy (FSHD) program as participant dosing commences in phase 2 FORGE trial. News release. Scholar Rock. September 2, 2026. Accessed September 18, 2026. https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-receives-fda-fast-track-designation-apitegromab
2. Staropoli J, Statland J, Johnson N, et al. Trial design for the Phase 2 FORGE study evaluating apitegromab in adults with facioscapulohumeral muscular dystrophy. Presented at: MDA Clinical & Scientific Conference; March 8-11, 2026; Orlando, Florida. Abstract 308.
3. Tawil R, Van Der Maarel SM. Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2006;34(1):1-15. doi:10.1002/mus.20522
4. Scholar Rock announces FDA approval of Isembyld (apitegromab-mstn), the first and only muscle-targeted treatment for children and adults with spinal muscular atrophy (SMA). Scholar Rock. News release. September 11, 2026. Accessed September 18, 2026. https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-announces-fda-approval-isembyldtm-apitegromab-mstn
5. Crawford TO, Servais L, Mercuri E, et al. Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2025;24(9):727-739. doi:10.1016/S1474-4422(25)00225-X