Scholar Rock Announces Apitegromab Achieves Primary Endpoint in Phase 3 SAPPHIRE Study for Spinal Muscular Atrophy Patients

Scholar Rock Announces Positive Phase 3 Results for Apitegromab in SMA Trials

Scholar Rock (SRRK), a late-stage biopharmaceutical company dedicated to developing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases linked to protein growth factors, has shared encouraging topline results from the Phase 3 SAPPHIRE clinical trial. This trial assessed the efficacy and safety of apitegromab, a muscle-targeted investigational therapy, in patients with SMA.

The trial achieved its primary endpoint, showing a statistically significant and clinically meaningful improvement in motor function for patients receiving apitegromab compared to those on placebo. This was evaluated using the Hammersmith Functional Motor Scale Expanded (HFMSE) standard among SMA patients who were receiving standard care therapies (such as nusinersen or risdiplam). The statistical analysis plan had predetermined that both the 10 mg/kg and 20 mg/kg doses of apitegromab would be assessed against placebo.

Key findings from the efficacy analysis include:

• In the main efficacy group (ages 2-12), patients treated with apitegromab (both doses combined) showed an average improvement of 1.8 points in HFMSE compared to placebo. For those on the 20 mg/kg dosage, the mean difference was 1.4 points, while the 10 mg/kg group exhibited a notable improvement of 2.2 points.
• Pharmacokinetic and pharmacodynamic data indicated similar levels of target engagement for both dosage groups.

The benefits of apitegromab were consistent across age groups, showing that 30% of treated patients improved by more than 3 points in HFMSE compared to only 12.5% in the placebo group. Improvements in motor function began as early as 8 weeks into treatment and were sustained at 52 weeks. Following the trial, a significant majority of participants chose to enroll in the ongoing ONYX open-label expansion study.

Dr. Jay Backstrom, President and CEO of Scholar Rock, expressed excitement over the results: “Our Phase 3 SAPPHIRE clinical study has demonstrated robust and clinically meaningful improvements in motor function in patients with SMA. We are committed to making apitegromab available to those in need as quickly as possible.”

Apitegromab was found to be well-tolerated among participants, with no significant differences in adverse events between dosing groups. No new safety concerns were identified, aligning with findings from the previous Phase 2 TOPAZ trial, which had a long-term treatment extension. Serious adverse events encountered were consistent with the patients’ underlying condition, and none were attributed to the therapy.

Dr. Jing Marantz, Chief Medical Officer at Scholar Rock, acknowledged the contributions of trial participants. “The positive results from SAPPHIRE, alongside over four years of data from the TOPAZ trial, underline the potential of apitegromab to offer meaningful improvements for a wide SMA population historically expected to decline over time.”

The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug, and Rare Pediatric Disease designations to apitegromab, while the European Medicines Agency (EMA) has offered similar designations. The company plans to submit regulatory applications for both the U.S. and EU in early 2025.

Kenneth Hobby, President of Cure SMA, noted the significance of these developments for the SMA community: “These results signify a critical milestone for those living with SMA, addressing some of the most pressing needs associated with the condition.”

Scholar Rock also indicated that further analyses of the complete Phase 3 SAPPHIRE data are ongoing, with plans to present detailed results at a medical conference in early 2025. Initial baseline characteristics from the trial will be shared at the upcoming Congress of the World Muscle Society in October 2024.

Upcoming Conference Presentation
Scholar Rock is set to present preliminary baseline characteristics from the SAPPHIRE trial:

Title: Apitegromab in Spinal Muscular Atrophy: Baseline Characteristics of Participants in Phase 3 SAPPHIRE Study
Presentation Type: Poster Presentation
Presenter: Thomas O. Crawford, M.D., Professor of Neurology and Pediatrics, Johns Hopkins University
Date and Time: Friday, October 11, 2024, at 3:45 PM CET
Location: Prague, Czech Republic