Apitegromab improves motor function in spinal muscular atrophy as early as week 8

Key takeaways:

• 30.4% of patients who received apitegromab had a 3-point or more improvement in motor function vs. 12.5% given placebo.
• Apitegromab was also associated with earlier motor function improvement vs. placebo.

Topline results from the phase 3 SAPPHIRE clinical trial showed that an investigational muscle-targeted therapy improved motor function in patients with spinal muscular atrophy compared with placebo as early as week 8.

The benefits were sustained at 1 year, manufacturer Scholar Rock reported in a press release.

According to the company, apitegromab, a fully human monoclonal antibody, led to “significant and clinically meaningful” motor function improvement based on the Hammersmith Functional Motor Scale – Expanded (HFMSE) in patients already receiving standard of care therapies such as nusinersen (Spinraza, Biogen) or risdiplam (Evrysdi, Genentech).

For the randomized, double-blind, placebo-controlled SAPPHIRE study, researchers examined the safety and efficacy of apitegromab in 156 nonambulatory patients aged 2 to 12 years who were diagnosed with types 2 and 3 spinal muscular atrophy (SMA) and prescribed current standard of care medications.

The patients were randomly assigned 1:1:1 to receive either 10 mg/kg apitegromab, 20 mg/kg apitegromab or placebo every 4 weeks by IV infusion for 1 year. Additionally, an exploratory population of 32 patients aged 13 to 21 years was randomly assigned 2:1 to receive either 20 mg/kg apitegromab or placebo.

In the main efficacy population, data showed a mean difference in change from baseline in HFMSE of 1.8 points for all patients receiving apitegromab compared with placebo. The exploratory treatment population scored a mean 1.4-point difference compared with its own placebo group, while a prespecified analysis of patients given the 10 mg/kg dose showed a mean improvement of 2.2 points compared with placebo.

The company further reported that 30.4% of patients who received apitegromab registered an improvement of at least 3 points on the HFMSE compared with 12.5% of patients in the placebo group at week 52.

Those receiving apitegromab showed earlier motor function improvement compared with placebo, a positive outcome that was observed at week 8 and persisted and expanded through week 52, according to the release.

Apitegromab was also well-tolerated across all age groups, the company said. Serious adverse events (SAEs) were consistent with the underlying disease and current standard of care, with no SAEs related to treatment. No discontinuations due to drug-related adverse events were recorded, according to the release.

“We are thrilled that apitegromab met the primary endpoint in our Phase 3 SAPPHIRE clinical study,” Jay Backstrom, MD, MPH, president and CEO of Scholar Rock, said in the release. “The results clearly demonstrate robust and clinically meaningful improvement in motor function in patients with SMA.”

Scholar Rock said it plans to submit a U.S. biologics license application as well as a European Union marketing authorization application during the first quarter of 2025.