Scholar Rock Presents New Data from Phase 3 SAPPHIRE Trial at 2025 MDA Conference
Scholar Rock, a leading late-stage biopharmaceutical company, has revealed promising new data from its Phase 3 SAPPHIRE trial at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference held in Dallas, Texas. Scholar Rock focuses on advancing innovative treatments for neuromuscular diseases, cardiometabolic disorders, and other serious conditions driven by protein growth factors.
The data shared at the conference sheds light on the efficacy and safety of apitegromab, an investigational muscle-targeted therapy aimed at improving motor function for patients with spinal muscular atrophy (SMA) who are receiving SMN-targeted therapies. The Phase 3 SAPPHIRE trial (NCT05156320) evaluated how apitegromab works in conjunction with existing treatments for SMA, offering hope for a clinically meaningful improvement in motor function for these patients.
Key Findings from the SAPPHIRE Trial
During the 2025 MDA Conference, Scholar Rock presented data from several clinical presentations focused on new analyses, including secondary endpoints, which provided further insights into the treatment’s potential.
In addition to previously announced results from October 2024, the SAPPHIRE trial demonstrated that apitegromab produced consistent and clinically meaningful benefits in motor function across multiple patient subgroups. These subgroups included variations in patient age, background therapy (SMN-targeted treatment), and the timing of SMN-targeted therapy initiation. Furthermore, efficacy was consistently observed across several important motor function outcome measures, including the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and World Health Organization (WHO) motor development milestones.
Dr. Thomas O. Crawford, Professor of Neurology and Pediatrics at Johns Hopkins University and Principal Investigator of the SAPPHIRE trial, emphasized the significance of these results, stating, “While SMN-targeting therapies offer dramatic gains, there remains residual weakness, and functional decline is now evident in many individuals with SMA. The SAPPHIRE trial findings are very exciting because they support the hypothesis that targeting muscle can provide functional improvement for patients with SMA who are already receiving SMN-targeted therapy.”
2025 MDA Conference Data Presentation Highlights
Primary Endpoint (HFMSE) Analysis
The SAPPHIRE trial achieved its primary endpoint with statistically significant and clinically meaningful improvement in motor function as measured by the HFMSE. The analysis demonstrated that patients receiving apitegromab showed an improvement in motor function compared to those receiving a placebo. Specifically, there was a 1.8-point mean improvement in HFMSE for patients receiving apitegromab (10 mg/kg and 20 mg/kg) versus placebo. This result was statistically significant (p=0.0192) across the primary efficacy population (ages 2-12). However, for patients receiving the 20 mg/kg dose, the improvement was smaller and did not reach statistical significance (p=0.1149).
The new analysis of the pooled population (ages 2-21) confirmed that apitegromab consistently improved HFMSE across different pre-specified patient subgroups. These included variations based on the type of SMN-targeted therapy, the age at initiation of SMN therapy, and geographic region.
Secondary Endpoints
The trial also examined secondary endpoints to assess additional motor function improvements. Among patients aged 2-12 receiving either 10 mg/kg or 20 mg/kg of apitegromab, several key findings emerged:
- Improved HFMSE Scores: A greater proportion of patients treated with apitegromab achieved a ≥3-point improvement in HFMSE scores compared to those on placebo (30.4% vs. 12.5%, respectively). This result was statistically significant (p=0.0156).
- Motor Function Consistency: Improvements in motor function were consistently observed across all five-point thresholds of HFMSE (ranging from ≥0 points to ≥4 points) at the 52-week mark.
- Other Motor Function Measures: Apitegromab also demonstrated consistent improvements in additional motor function outcome measures, including the RULM and WHO motor development milestones.
Safety and Pharmacokinetics (PK)
In terms of safety, apitegromab was generally well tolerated by patients across all age groups. No significant safety concerns were raised, and the treatment was consistent with the expected safety profile, with no clinically relevant differences based on dose. Serious adverse events (SAEs) were typically related to the underlying disease or the use of SMN-targeted therapies, with no SAEs directly attributed to apitegromab.
Pharmacokinetic (PK) and pharmacodynamic (PD) analyses revealed similar levels of target engagement for both the 10 mg/kg and 20 mg/kg dose groups, further supporting the consistency of apitegromab’s action across different doses.
Looking Forward: Apitegromab’s Potential in SMA Treatment
Scholar Rock’s CEO, Dr. Jay Backstrom, expressed enthusiasm about the trial’s results, stating, “We are excited to present the SAPPHIRE data at the MDA conference, reinforcing apitegromab’s potential as a transformative muscle-targeted therapy for individuals living with SMA. Progressive muscle weakness continues to significantly impact the daily lives of SMA patients, despite current SMN-targeted treatments. The data from this trial show a clear clinical benefit and demonstrate that apitegromab can provide further improvements in motor function, offering hope for a better quality of life for these patients.”
With these promising results, Scholar Rock is now focused on preparing to commercialize apitegromab in the United States, Europe, and other regions where it could benefit patients with SMA. The SMA community has been calling for additional therapeutic options, and apitegromab’s positive data suggests t
About 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 the Phase 3 SAPPHIRE Trial
SAPPHIRE was a randomized, double-blind, placebo-controlled Phase 3 clinical trial that evaluated the safety and efficacy of apitegromab in nonambulatory patients with Types 2 and 3 SMA who were receiving current standard of care (either nusinersen or risdiplam). SAPPHIRE enrolled 156 patients aged 2-12 years old in the main efficacy population. These patients were randomized 1:1:1 to receive either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo by intravenous (IV) infusion every 4 weeks for 12 months. An exploratory population including 32 patients aged 13-21 years old was also evaluated. These patients were randomized 2:1 to receive either apitegromab 20 mg/kg or placebo every 4 weeks for 12 months.
The SAPPHIRE trial met its primary endpoint for the main efficacy population with a statistically significant 1.8-point improvement (p=0.0192) based on apitegromab combined dose (10 mg/kg and 20 mg/kg) and standard of care (SOC) versus placebo and SOC (Hochberg multiplicity adjustment) as measured by the Hammersmith Functional Motor Scale-Expanded at week 52. Patients receiving 20 mg/kg of apitegromab (n=53) showed a 1.4 point mean difference compared to placebo (p=0.1149). Additional details can be found here.
About Scholar Rock
Scholar Rock is a biopharmaceutical company that discovers, develops, and delivers life-changing therapies for people with serious diseases that have high unmet need. As a global leader in the biology of the transforming growth factor beta (TGFβ) superfamily and named for the visual resemblance of a scholar rock to protein structures, the clinical-stage company is focused on advancing innovative treatments where protein growth factors are fundamental. Over the past decade, Scholar Rock has created a pipeline with the potential to advance the standard of care for neuromuscular disease, cardiometabolic disorders, cancer, and other conditions where growth factor-targeted drugs can play a transformational role.
This commitment to unlocking fundamentally different therapeutic approaches is powered by broad application of a proprietary platform, which has developed novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity. By harnessing cutting-edge science in disease spaces that are historically under-addressed through traditional therapies, Scholar Rock works every day to create new possibilities for patients. Learn more about our approach at ScholarRock.com and follow @ScholarRock and on LinkedIn.
Scholar Rock® is a registered trademark of Scholar Rock, Inc.hat it could become an important new treatment for individuals living with this challenging condition.
