Scholar Rock (NASDAQ: SRRK) has announced positive topline results from the phase 3 Sapphire clinical trial (NCT05156320) evaluating the efficacy and safety of apitegromab, an investigational muscle-targeted therapy, in patients with spinal muscular atrophy (SMA).
The study achieved its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement for apitegromab versus placebo in motor function as measured by the gold standard Hammersmith Functional Motor Scale Expanded (HFMSE) in SMA patients on chronic dosing of standard of care therapies. In the main efficacy population (ages 2-12), the mean difference in change from baseline in HFMSE was 1.8 points for all patients receiving apitegromab 10 mg/kg and 20 mg/kg compared to placebo. Patients receiving 20 mg/kg of apitegromab showed a 1.4 point mean difference compared to placebo, and the prespecified analysis of the 10 mg/kg dose showed that patients receiving 10 mg/kg of apitegromab showed an improvement of 2.2 points compared to placebo.
Specifically, 30.4% of patients receiving apitegromab had >3 point improvement in HFMSE versus 12.5% of patients on placebo. Patients receiving apitegromab demonstrated early motor function improvement compared to placebo from the first measured time point at 8 weeks, with the benefit expanding at 52 weeks as measured by HFMSE. Following trial completion, 98 percent of Sapphire patients (185/188) enrolled in the ongoing Onyx open-label expansion study.
In terms of safety, treatment with apitegromab was well-tolerated across all age groups, and there were no clinically relevant differences in the adverse event profile by dose, 10 mg/kg versus 20 mg/kg. No new safety findings were observed in the Sapphire clinical trial, and serious adverse events (SAEs) were consistent with the underlying disease and current standard of care received by patients, with no SAEs assessed as related to apitegromab. There were no study drug discontinuations due to adverse events.
Scholar Rock plans to submit a U.S. Biologics License Application (BLA) and a European Union Marketing Authorisation Application (MAA) in Q1 2025. 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.
"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, M.D., MPH, President and Chief Executive Officer of Scholar Rock. "At Scholar Rock, we are working with urgency to deliver the potentially transformative benefits of apitegromab to children and adults with SMA in the US, Europe, and around the world."
Analyses of the full phase 3 Sapphire data are ongoing, and Scholar Rock plans to present detailed results at an upcoming medical conference in early 2025. Preliminary baseline characteristics from the trial will be presented during a poster presentation at the upcoming 29th Annual Congress of the World Muscle Society on Friday, October 11, 2024, in Prague, Czech Republic.
It's a significant development for patients with SMA and their families, as these positive trial results mark a critical milestone for the SMA community. Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disease that afflicts an estimated 30,000 to 35,000 people in the United States and Europe. The disease is characterized by the loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk, and progressive muscle weakness. The development of a therapy that directly addresses the progressive muscle weakness in SMA represents a significant unmet need in the treatment of the disease. Today the company's shares have moved 315.8% to a price of $30.85. Check out the company's full 8-K submission here.
