Scholar Rock Holding Corporation announced positive top-line results from its Phase 3 SAPPHIRE clinical trial, revealing that apitegromab met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in motor function in patients with spinal muscular atrophy (SMA). The trial's success has paved the way for Scholar Rock to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) and a marketing authorization application (MAA) to the European Medicines Agency (EMA) in the first quarter of 2025. If approved, the company anticipates a U.S. commercial launch in the fourth quarter of 2025.
The SAPPHIRE trial (NCT05156320) evaluated the efficacy and safety of apitegromab, a muscle-targeted therapy, in SMA patients already receiving standard of care treatments like nusinersen or risdiplam. The study included 156 patients aged 2-12 years in the main efficacy population and an exploratory population of patients aged 13-21 years.
Key Findings from the SAPPHIRE Trial
The primary endpoint, measured by the Hammersmith Functional Motor Scale Expanded (HFMSE), revealed a mean difference of 1.8 points (p = 0.0192) relative to placebo in the combined apitegromab groups. A pre-specified analysis of the 10 mg/kg dose group showed an even greater improvement of 2.2 points (p = 0.0121) on HFMSE compared to placebo.
Notably, 30% of patients receiving apitegromab experienced a greater than three-point improvement in HFMSE compared to only 12.5% of those on placebo. This clinically meaningful benefit was observed as early as eight weeks after treatment initiation and sustained through 52 weeks.
Safety and Tolerability
Apitegromab was well-tolerated, with a safety profile consistent with previous studies. There were no study discontinuations due to adverse events, and 98% of participants who completed the trial enrolled in the ongoing ONYX open-label extension study.
Expert Commentary
"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," said Jay Backstrom, MD, MPH, President and Chief Executive Officer of Scholar Rock.
Kenneth Hobby, President of Cure SMA, added, "These encouraging trial results mark a critical milestone for the SMA community. Declining motor function and hopes for reversing losses associated with muscle weakness are significant unmet needs, impacting activities of daily living... We need an approved therapy that can support motor function and further improve daily activities for people with SMA."
Apitegromab's Mechanism of Action
Apitegromab is a monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle. This mechanism aims to increase muscle mass and improve motor function in SMA patients.
Market Impact and Future Plans
Following the announcement of the positive results, Scholar Rock's stock price surged. The company is also investigating apitegromab in a Phase 2 trial for obesity, exploring its potential to preserve lean muscle mass during weight loss.
With regulatory submissions planned for Q1 2025, Scholar Rock is poised to potentially transform the treatment landscape for SMA, offering a new muscle-targeted approach to improve motor function and quality of life for patients.
