Phase 3 apitegromab topline data in SMA types 2, 3 due by year’s end

Treatment targets myostatin, a protein involved in suppressing muscle growth

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Scholar Rock remains on track to report topline results later this year from its ongoing Phase 3 clinical trial of apitegromab in children and young adults with spinal muscular atrophy (SMA) types 2 or 3.

Apitegromab is an antibody that targets myostatin, a protein involved in suppressing muscle growth. This should boost muscle strength and improve patients’ motor function.

“In 2023, Scholar Rock made significant progress across our industry-leading antimyostatin pipeline, and we are poised for a transformational year ahead. We remain on track to release topline data for our Phase 3 SAPPHIRE trial of apitegromab in spinal muscular atrophy in the fourth quarter of 2024, which if successful, will be the foundation of our neuromuscular franchise,” Jay Backstrom, MD, Scholar Rock’s president and CEO, said in a company financial update.  “As the only company to show clinical proof of concept in SMA with our selective antimyostatin approach, we are well positioned to further extend our leadership with a potential launch in SMA … in 2025.”

SMA is marked by a lack of the SMN protein, which causes motor nerve cells, which control muscle movement, to die. As a result, people with SMA develop muscle weakness and wasting.

Myostatin is mainly present in skeletal muscles, those used for movement. It limits muscle growth to maintain a healthy muscle mass. Apitegromab blocks myostatin’s transformation to an active form, which should increase muscle mass production in SMA and improve patients’ motor function.

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Topline results of apitegromab

The Phase 3 SAPPHIRE trial (NCT05156320) enrolled up to 204 patients, ages 2 -21, with SMA type 2 or 3 who were unable to walk, but could sit independently, in more than 50 sites in the U.S. and Europe. All were being treated with Spinraza (nusinersen) or Evrysdi (risdiplam). Its primary goal is to compare apitegromab’s effectiveness in boosting motor function against a placebo after a year of treatment using the Hammersmith Functional Motor Scale Expanded (HFMSE).

The SAPPHIRE trial follows positive data from the proof-of-concept Phase 2 TOPAZ trial (NCT03921528), which assessed the safety and efficacy of apitegromab in 58 children and young adults, ages 2-21, with SMA type 2 or 3. Participants received two doses of apitegromab, 2 and 20 mg/kg.

One year of treatment with apitegromab, either alone or as an add-on to Spinraza, led to clinically meaningful improvements in motor function, as assessed by the HFMSE, in some patients. These gains were mainly seen in patients who were younger when they started therapy. The higher dose led to greater benefits, including in those who weren’t able to walk.

Those who completed both SAPPHIRE and TOPAZ were eligible to enter the ONYX study, which is evaluating apitegromab’s long-term safety and efficacy. The study is ongoing, according to Scholar Rock, which announced it will launch a Phase 2 proof-of-concept trial with apitegromab as an adjunctive therapy to treat obesity the middle of this year.