Apitegromab hits goal of boosting motor function in Phase 3 trial
Scholar Rock’s apitegromab led to motor function improvements over a year of treatment in young adults and children with spinal muscular atrophy (SMA) type 2 or 3 who could sit independently and were on stable standard of care, but unable to walk.
That’s according to top-line data from SAPPHIRE (NCT05156320), a Phase 3 clinical study that’s testing the safety and efficacy of apitegromab when given as an intravenous (into-the-vein) infusion once every four weeks as an add-on to Biogen’s Spinraza (nusinersen) or Roche’s Evrysdi (risdiplam).
After about a year, a greater proportion of patients taking apitegromab had a three-point increase or more on the Hammersmith Functional Motor Scale Expanded (HFMSE), indicating an improvement in motor function, compared with patients on a placebo (30.4% vs. 12.5%). Improvements were seen as early as eight weeks.
“We are thrilled that apitegromab met the primary endpoint in our Phase 3 SAPPHIRE clinical study,” Jay Backstrom, MD, Scholar Rock’s president and CEO, said in a company press release. “The results clearly demonstrate robust and clinically meaningful improvement in motor function in patients with SMA.”
Positive data align with improvements seen in earlier Phase 2 TOPAZ study
These data align with improvements in motor function seen for up to four years in the earlier Phase 2 TOPAZ study (NCT03921528), supporting the company’s plans to file for approval in the U.S. and the European Union in the first quarter of 2025.
“We look forward to submitting our applications,” said Jing Marantz, MD, PhD, chief medical officer at Scholar Rock.
For Marantz, these data show the “potentially transformative benefit of apitegromab to drive clinically meaningful improvements in motor function as measured by HFMSE in a broad SMA population, where motor function would normally be expected to generally decline over time.”
In SMA, a lack of SMN protein causes motor neurons, which are the nerve cells that control voluntary movement, to become damaged and die over time. This results in gradual muscle weakness and loss of muscle mass, leading to problems with breathing, eating, and walking.
“Declining motor function and hopes for reversing losses associated with muscle weakness are significant unmet needs, impacting activities of daily living, from breathing, eating, self-care, to working and social interactions,” said Kenneth Hobby, president of Cure SMA. “We need an approved therapy that can support motor function and further improve daily activities for people with SMA.”
Apitegromab designed to block inactive form of myostatin
Apitegromab is an antibody designed to block myostatin’s inactive form, preventing it from becoming active. Myostatin is a protein that limits muscle growth, so reducing the amount of its active form is expected to increase muscle mass and improve motor function.
The SAPPHIRE study enrolled 188 young adults and children with SMA type 2 or 3, including 156 patients, ages 2-12, in the main group, and 32 patients, ages 13-21, in an exploratory group. In addition to their standard of care, Spinraza or Evrysdi, patients were randomly assigned to receive apitegromab or a placebo via intravenous infusion every four weeks for 52 weeks, or about a year.
On average, patients were 3.2 years old when they were first started on disease-modifying medications for SMA. Over two-thirds (77.6%) were on Spinraza, and most (83.3%) had three copies of SMN2, a back-up gene that allows for production of a small amount of SMN.
Apitegromab was available at a dose of 10 or 20 mg/kg. Data for both doses were analyzed together and separately. Patients ages 2-12, on either dose, showed a 1.8-point increase on the HFMSE compared with those on the placebo. Those receiving the 10 mg/kg dose showed a 2.2-point improvement, while patients on the 20 mg/kg dose showed a 1.4-point improvement, which was not considered statistically significant.
Apitegromab was well tolerated across all ages, with no new safety issues. Serious side effects were related to the disease or the standard of care, but not to apitegromab. No patients stopped treatment, with the majority (98.4%) enrolling in an ongoing open-label expansion study called ONYX (NCT05626855).
These data will be presented at the 29th Annual Congress of the World Muscle Society on Oct. 11 in Prague, Czech Republic.
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