Scholar Rock Presents Comprehensive Phase 3 SAPPHIRE Trial Data at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference
Scholar Rock, a late-stage biopharmaceutical company committed to advancing groundbreaking treatments for neuromuscular diseases, cardiometabolic disorders, and other serious conditions influenced by protein growth factors, has announced the presentation of new efficacy and safety data from its Phase 3 pivotal SAPPHIRE trial (NCT05156320). The findings will be showcased in multiple clinical presentations at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Dallas, Texas.
The Phase 3 SAPPHIRE trial was designed to assess the efficacy and safety of apitegromab, an investigational muscle-targeted therapy developed to enhance motor function in individuals with spinal muscular atrophy (SMA) who are receiving SMN-targeted treatments. Apitegromab’s potential to provide clinically meaningful improvement in motor function has positioned it as a promising therapeutic candidate within the SMA treatment landscape.
Key Highlights from the SAPPHIRE Trial Presentations at the 2025 MDA Conference
Scholar Rock’s latest presentations at the MDA conference bring forth a wealth of new data, including detailed secondary endpoint analyses. In addition to meeting the trial’s primary endpoint—an achievement initially reported in October 2024—apitegromab exhibited a strong and consistent benefit in motor function across multiple pre-specified patient subgroups. These subgroups were categorized by factors such as patient age, SMA background therapy, and age at initiation of SMN-targeted therapy.
Moreover, efficacy results remained consistent across various standardized patient outcome measures of motor function, including the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and World Health Organization (WHO) motor development milestones. The consistency of these findings reinforces apitegromab’s potential to address an unmet need in SMA treatment.
Expert Insights on SAPPHIRE Trial Results
Dr. Thomas O. Crawford, Professor of Neurology and Pediatrics at Johns Hopkins University and Principal Investigator of the SAPPHIRE trial, highlighted the importance of these findings:
“While SMN-targeted therapies have been revolutionary for SMA treatment, they do not fully restore lost motor function. Many patients continue to experience residual weakness and functional decline, impacting their ability to perform everyday activities and maintain independence. The SAPPHIRE trial results suggest that targeting muscle directly with apitegromab offers significant functional benefits, complementing existing SMN-targeted therapies. Most importantly, the observed improvements were consistent across multiple validated clinical metrics used to evaluate SMA patient outcomes.”
Detailed Findings from the SAPPHIRE Trial Data Presentation
Primary Endpoint: HFMSE Analysis
- The Phase 3 SAPPHIRE trial met its primary endpoint by demonstrating statistically significant and clinically meaningful improvements in motor function among SMA patients receiving apitegromab in combination with standard-of-care therapies (nusinersen or risdiplam).
- Patients in the main efficacy population (ages 2-12) treated with apitegromab (10 mg/kg and 20 mg/kg) showed a mean difference in HFMSE score improvement of 1.8 points compared to placebo (p=0.0192).
- Among those receiving the 20 mg/kg dose, the mean difference was 1.4 points compared to placebo (p=0.1149), further supporting the therapy’s dose-responsive effect.
- New analysis in a broader pooled population (ages 2-21) reinforced the treatment’s efficacy across various subgroups, including type of SMN-targeted therapy and age at SMN therapy initiation, as well as across different geographic regions.
Secondary Endpoints: Additional Motor Function Improvements
- For children ages 2-12 receiving apitegromab at either dosage, further improvements were observed across secondary endpoints:
- A greater proportion of apitegromab-treated patients achieved a clinically meaningful improvement of ≥3 points in their HFMSE scores compared to placebo (odds ratio of 3.0, nominal p-value = 0.0256).
- Specifically, 30.4% of apitegromab-treated patients achieved this ≥3-point improvement, compared to 12.5% of patients in the placebo group (nominal p-value = 0.0156).
- Consistent benefits were seen across all HFMSE improvement thresholds (≥0 to ≥4 points) over 52 weeks of treatment.
- Improvements were also evident in other motor function outcome measures, including:
- Revised Upper Limb Module (RULM)
- World Health Organization (WHO) motor development milestones
Safety and Pharmacokinetics (PK) Profile of Apitegromab
- Apitegromab was well-tolerated across all age groups, aligning with its established safety profile.
- No clinically significant differences were observed between the 10 mg/kg and 20 mg/kg dose groups in terms of safety outcomes.
- Serious adverse events (SAEs) were consistent with the underlying disease and existing SMN-targeted therapies, with no SAEs attributed to apitegromab treatment.
- PK and pharmacodynamic (PD) data confirmed consistent target engagement at both tested dose levels.
Scholar Rock’s Vision for Apitegromab Commercialization
Dr. Jay Backstrom, President and CEO of Scholar Rock, emphasized the broader implications of these findings:
“The SAPPHIRE data represent a pivotal milestone in the journey to bring apitegromab to market. Despite advances in SMN-targeted treatments, progressive muscle weakness continues to limit many individuals with SMA. The SMA community has long expressed a need for additional therapeutic options that further enhance motor function. The consistency of benefit seen across key outcome measures underscores the transformative potential of apitegromab. We are now prioritizing efforts to bring this therapy to patients in the U.S., Europe, and additional global markets where there is a pressing need for improved SMA treatment options.”
