Scholar Rock Advances Apitegromab Development for FSHD with FDA Fast Track and Orphan Drug Designations
Scholar Rock (NASDAQ: SRRK), a global biopharmaceutical company focused on developing therapies for rare, severe, and debilitating neuromuscular diseases, has announced important regulatory and clinical development progress for apitegromab, its investigational muscle-targeted therapy for people living with facioscapulohumeral muscular dystrophy (FSHD).
The U.S. Food and Drug Administration (FDA) has granted both Fast Track Designation and Orphan Drug Designation to apitegromab for the potential treatment of people with FSHD. At the same time, Scholar Rock confirmed that participant dosing has begun in the Phase 2 FORGE clinical trial, an important step in the company’s effort to evaluate the therapeutic potential of apitegromab in this progressive neuromuscular disorder.
The developments strengthen Scholar Rock’s broader strategy of leveraging its expertise in myostatin biology to develop treatments designed to improve muscle health and physical function in patients affected by serious neuromuscular diseases.
Advancing a Potential Therapy for FSHD
FSHD is a hereditary and progressive neuromuscular disease characterized by muscle atrophy, weakness, and deterioration in physical function over time. The disease can substantially affect mobility and the ability to perform everyday activities, creating a significant burden for patients and their families.
Despite ongoing research into the underlying biology of FSHD, treatment options remain limited, underscoring the need for new therapeutic approaches that could preserve or improve muscle function. Scholar Rock is investigating whether targeting muscle biology through inhibition of myostatin activation could offer a differentiated approach to addressing the consequences of the disease.
Apitegromab is an investigational fully human monoclonal antibody designed to inhibit the activation of myostatin. Myostatin is a naturally occurring protein involved in regulating muscle growth. By selectively interfering with myostatin activation, apitegromab is being developed with the goal of promoting muscle growth and potentially improving physical capabilities.
The company believes this mechanism could be particularly relevant to diseases in which progressive muscle loss and weakness are major contributors to functional decline.
FDA Fast Track and Orphan Drug Designations
The FDA’s decision to grant Fast Track and Orphan Drug designations represents an important milestone for Scholar Rock’s FSHD program.
Fast Track Designation is intended for investigational therapies that are being developed to treat serious or life-threatening conditions and that have the potential to address significant unmet medical needs. The designation is designed to facilitate communication between developers and the FDA and can help support an accelerated development and review process for eligible therapies.
For Scholar Rock, the designation recognizes the potential importance of advancing new treatment options for individuals living with FSHD. Although Fast Track status does not guarantee approval or establish the efficacy or safety of apitegromab, it provides a regulatory framework intended to support efficient development of therapies addressing serious unmet medical needs.
Apitegromab has also received Orphan Drug Designation for FSHD. Orphan Drug Designation is generally intended to support the development of therapies for rare diseases and conditions affecting relatively small patient populations. The designation can provide certain incentives intended to encourage pharmaceutical development in areas where commercial and scientific challenges may otherwise limit investment.
Together, the two designations highlight the company’s focus on advancing apitegromab through clinical development for a rare neuromuscular condition.
Phase 2 FORGE Trial Begins Participant Dosing
Alongside the regulatory announcement, Scholar Rock reported that participant dosing is now underway in the Phase 2 FORGE clinical trial.
FORGE is designed as a randomized, double-blind, placebo-controlled, multicenter study intended to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of apitegromab when administered as a monotherapy in adults with genetically confirmed FSHD.
The study is expected to enroll approximately 60 participants. Patients will be randomized in a one-to-one ratio to receive either apitegromab at a dose of 10 mg/kg or placebo. Treatment will be administered intravenously once every four weeks over a 52-week period.
The trial is registered as NCT07435129 and is designed to provide researchers with clinical data across multiple measures of muscle composition, treatment response, safety, and potentially functional benefit.
The primary endpoint of the FORGE study is the percentage change from baseline in total lean muscle volume (LMV), measured by magnetic resonance imaging (MRI) at Week 52.
The use of MRI-based lean muscle volume as the primary measure is intended to provide an objective assessment of changes in muscle tissue during treatment. Changes in muscle composition and volume can offer important information when evaluating therapies designed to influence muscle growth or preservation.
Additional Measures of Muscle Health and Treatment Response
In addition to the primary endpoint, the FORGE study will assess several secondary and exploratory measures.
One secondary endpoint will evaluate the percentage change from baseline in total lean muscle volume at Week 24. This earlier assessment could provide information regarding the timing and trajectory of potential treatment-related changes in muscle volume.
The study will also evaluate additional muscle parameters, including muscle fat fraction, at Weeks 24 and 52. Measuring muscle fat fraction can provide additional information about changes in muscle composition and may help researchers better understand the biological effects of treatment.
Safety and tolerability will also be assessed throughout the study. As with any investigational therapy, monitoring safety is a fundamental component of clinical development and will help determine the overall benefit-risk profile of apitegromab in adults with FSHD.
Exploratory endpoints will further assess potential treatment effects and may provide additional insight into whether changes in muscle characteristics translate into meaningful functional outcomes for patients.
Scientific Rationale for Apitegromab in FSHD
Scholar Rock’s decision to investigate apitegromab in FSHD is supported by translational preclinical research and findings from previous scientific literature.
According to the company, preclinical studies using the FLExDUX4 mouse model of FSHD demonstrated that a murine form of apitegromab increased muscle mass, strength, and endurance.
The FLExDUX4 model is considered an important preclinical model for investigating FSHD biology and potential therapeutic approaches. Results from such models can provide researchers with evidence regarding whether a particular mechanism may have the potential to influence disease-relevant biological or functional characteristics.
Scholar Rock has also pointed to evidence suggesting that anabolic stimuli may result in muscle hypertrophy and improved motor function in FSHD. Based on this scientific rationale, the company believes that enhancing muscle-related biology through myostatin pathway modulation could potentially have meaningful implications for individuals affected by the disease.
However, preclinical findings do not necessarily predict clinical efficacy in humans. The FORGE trial is therefore an important step in determining whether the effects observed in experimental models can be translated into measurable benefits for people living with FSHD.
Company Leadership Highlights Development Potential
David L. Hallal, Chairman and Chief Executive Officer of Scholar Rock, described the FDA designations as an important recognition of the need for new treatment options for the FSHD community.
Hallal also emphasized that the start of participant dosing in FORGE brings the company closer to evaluating the broader potential of its myostatin platform in another serious neuromuscular disease.
The company views the FSHD program as part of its larger effort to apply its expertise in myostatin biology to diseases in which muscle weakness and loss of function have a substantial impact on patients.
Akshay Vaishnaw, M.D., Ph.D., President of Research and Development at Scholar Rock, highlighted the preclinical evidence supporting the program. He noted that the company’s findings from the FlexDux4 model, together with prior scientific literature, provide a rationale for investigating the potential of anabolic stimulation in FSHD.
Vaishnaw also emphasized the design of the FORGE study, which combines assessments of lean muscle volume with a range of exploratory functional endpoints. According to Scholar Rock, this approach is intended to provide a broad evaluation of apitegromab and help determine whether changes in muscle characteristics may translate into meaningful functional outcomes.
A Potentially Important Step in FSHD Drug Development
The initiation of dosing in FORGE marks a transition for apitegromab from preclinical investigation into a dedicated clinical study in FSHD. The trial will generate human clinical data that could help determine the potential of myostatin inhibition as a treatment strategy for this rare and progressive disease.
The combination of objective MRI-based measures, muscle composition assessments, safety evaluations, and exploratory functional outcomes could provide a comprehensive picture of the investigational therapy’s effects.
For the FSHD community, the development of new treatment approaches remains an important priority because progressive muscle weakness can significantly affect independence, mobility, and quality of life. Therapies capable of increasing or preserving functional muscle could potentially address an important component of the disease burden.
At this stage, apitegromab remains investigational, and its safety and efficacy for FSHD have not been established. Results from the Phase 2 FORGE study will be important in determining whether the preclinical rationale and biological mechanism translate into clinically meaningful outcomes in patients.
With FDA Fast Track and Orphan Drug designations now secured and participant dosing underway, Scholar Rock is continuing to advance apitegromab through clinical development. The company expects the FORGE trial to provide important evidence regarding the therapy’s effects on muscle volume, muscle composition, safety, and potential functional outcomes.
The progress also reinforces Scholar Rock’s broader commitment to developing therapies based on its expertise in myostatin biology. As the FORGE study progresses, its findings could help define the potential role of apitegromab in FSHD and contribute to the ongoing search for innovative treatment options for people living with rare neuromuscular diseases.
bout Apitegromab
Apitegromab is an investigational fully human monoclonal antibody inhibiting myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. It is the first muscle-targeted treatment candidate in spinal muscular atrophy (SMA) to demonstrate clinical success in a pivotal Phase 3 clinical trial.
Myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species, including humans. Scholar Rock believes that its highly selective targeting of pro- and latent forms of myostatin with apitegromab may lead to a clinically meaningful improvement in motor function in patients with SMA.
The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab for the treatment of SMA. Apitegromab has not been approved for any use by the FDA or any other regulatory agency.
About Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and debilitating hereditary neuromuscular disease characterized by muscle atrophy, weakness, and functional decline. The disease typically affects muscles of the face, shoulders, upper arms, trunk, and lower extremities, often resulting in impaired mobility, reduced independence, chronic pain, fatigue, and diminished quality of life.
The symptoms of FSHD can vary in both presentation and severity. The diagnosed prevalence of FSHD is estimated to be 1 in 20,000 individuals, suggesting there are approximately 40,000 people living with FSHD in the United States and European Union. However, the disease is underdiagnosed. There are currently no approved therapies for the treatment of FSHD.
About Scholar Rock
Scholar Rock is a late-stage biopharmaceutical company focused on developing and commercializing apitegromab for children and adults with spinal muscular atrophy (SMA) and other rare, severe and debilitating neuromuscular diseases. As a global leader in myostatin biology, a field focused on proteins that regulate muscle mass, the biopharmaceutical company is named for the visual resemblance of a scholar rock to protein structures.
Our commitment to unlock fundamentally different treatment approaches is powered by broad application of a proprietary platform, which has developed novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity. Scholar Rock works every day to create new possibilities for patients through its highly innovative anti-myostatin program, including opportunities in additional rare neuromuscular diseases. Learn more atScholarRock.comand follow @ScholarRock on X and on LinkedIn.