Scholar Rock: Apitegromab Successful in Phase 3 SMA Study

CAMBRIDGE, MA, USA I October 07, 2024 I Scholar Rock (NASDAQ: SRRK), a biopharmaceutical company in the advanced stages of developing treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases, has announced promising results from its Phase 3 SAPPHIRE clinical trial (NCT05156320). This trial tested the efficacy and safety of apitegromab, an experimental muscle-targeted therapy, in patients with SMA.

The Phase 3 SAPPHIRE trial successfully met its primary endpoint, showing a statistically significant and clinically meaningful improvement in motor function for patients treated with apitegromab compared to those given a placebo. Motor function improvements were measured using the Hammersmith Functional Motor Scale Expanded (HFMSE). Both the 10 mg/kg and 20 mg/kg doses of apitegromab demonstrated similar pharmacological profiles, allowing the statistical analysis to compare these doses combined against the placebo, as well as each dose individually. The prespecified statistical analysis plan, which included a Hochberg multiplicity adjustment, required a rigorous p-value threshold (≤0.025) to achieve statistical significance.

Results indicated that 30% of patients on apitegromab experienced more than a three-point improvement in HFMSE scores, compared to 12.5% of those on placebo. The apitegromab group showed early improvements in motor function as soon as eight weeks into the trial, with benefits growing by the 52-week mark. Notably, 98 percent of the patients from the SAPPHIRE trial (185 out of 188) have enrolled in the ongoing ONYX open-label extension study.

Jay Backstrom, M.D., MPH, President and CEO of Scholar Rock, expressed enthusiasm about the trial results, stating, "We are thrilled that apitegromab met the primary endpoint in our Phase 3 SAPPHIRE clinical study. The results clearly demonstrate robust and clinically meaningful improvement in motor function in patients with SMA."

The safety profile of apitegromab was also favorable. Across all age groups, the therapy was well-tolerated, with no significant differences in adverse events between the 10 mg/kg and 20 mg/kg doses. No new safety concerns were noted, and the serious adverse events observed were consistent with SMA's underlying disease and current standard treatments. Importantly, no SAEs were linked to apitegromab, and there were no discontinuations due to adverse events.

Jing Marantz, M.D., Ph.D., Chief Medical Officer at Scholar Rock, acknowledged the contributions of the trial participants and their families, stating, "The positive Phase 3 SAPPHIRE trial, along with over four years of TOPAZ clinical trial data, clearly demonstrate the potentially transformative benefit of apitegromab to drive clinically meaningful improvements in motor function."

Scholar Rock plans to submit applications to the FDA and the EMA in the first quarter of 2025, following the receipt of Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA, and Priority Medicines (PRIME) and Orphan Medicinal Product designations from the EMA for apitegromab.

Kenneth Hobby, President of Cure SMA, highlighted the significance of these results for the SMA community, emphasizing the need for approved therapies that can support motor function and improve daily living activities for those affected by the disease.

Detailed results from the full Phase 3 SAPPHIRE data are still being analyzed and are expected to be presented at an upcoming medical conference in early 2025. Preliminary baseline characteristics from the trial will be showcased at the 29th Annual Congress of the World Muscle Society on October 11, 2024, in Prague, Czech Republic.

About Apitegromab, it is an investigational monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle, showing promise in improving motor function in SMA patients. Scholar Rock continues to advance its innovative treatments to address critical unmet needs in various serious diseases.