Muscle gains with apitegromab still seen in TOPAZ, Phase 3 data on way
Should results of a Phase 3 trial of apitegromab, a muscle-directed therapy for spinal muscular atrophy, be positive when released later this year as expected — supporting the add-on therapy being approved — apitegromab could be available to U.S. patients in 2025, Scholar Rock, its developer, announced.
“We look forward to reporting topline data from the Phase 3 SAPPHIRE trial of apitegromab in SMA in the fourth quarter of this year,” Jay Backstrom, MD, president and CEO of Scholar Rock, said in a company press release.
Scholar Rock also released four-year data covering SMA patients who had enrolled in a now-completed Phase 2 study of apitegromab, and who had continued with treatment by entering a long-term extension trial.
“With the only muscle-targeted program to demonstrate clinical proof-of-concept in SMA, our confidence in our lead program apitegromab continues to be supported by the clinical data generated over the past four years” in company-sponsored clinical trials, Backstrom added.
Apitegromab aims to promote better strength, mobility in SMA patients
The Phase 3 SAPPHIRE trial (NCT05156320) has enrolled 188 children and young adults with SMA type 2 or type 3, all without the ability to walk but able to sit independently. Patients are being given monthly infusions of apitegromab or a placebo for one year, on top of treatment with the approved therapies Spinraza (nusinersen) or Evrysdi (risdiplam). The study’s main goal is to assess the impact of apitegromab on motor function measures.
Apitegromab is designed to block the activity of myostatin, a protein that normally acts to limit muscle growth. By inhibiting myostatin, apitegromab aims to promote SMA muscle repair, allowing patients to attain better strength and mobility. The therapy is designed for use with treatments like Spinraza and Evrysdi that target the root cause of SMA, which is a deficit of the SMN protein.
The experimental muscle-strengthening therapy showed proof-of-concept in the Phase 2 and open-label TOPAZ clinical trial (NCT03921528), which tested apitegromab as an add-on to Spinraza for one year in patients ages 2 through 21.
Most enrolled in TOPAZ — 35 of its 58 patients — had lost the ability to walk but could sit independently.
Continuous motor gains seen over 4 years in nonambulatory TOPAZ patients
New four-year data covers the nonambulatory patients who continued with apitegromab in the extension study.
These children and young adults are being assessed with two main measures of motor function: the Hammersmith Functional Motor Scale Expanded (HFMSE), which assesses overall motor function, and the Revised Upper Limb Module (RULM), which specifically assesses the function of the arms and hands.
A total of 33 nonambulatory patients remained in the study over four years. The efficacy analyses, however, excluded 11 who underwent surgery for scoliosis during the trial, since this type of surgery can cause measures of motor function to yield unreliable results.
Continuous improvements were seen in both standardized motor scores over the treatment years. For HFMSE, average scores improved by 3.6 points after one year, 4.2 points at two years, four points at three years, and 5.3 points at four years. For RULM, the average improvement was 1.3 points at one year, 2.3 points at two years, 2.4 points at three years, and 3.6 points at four years.
Focusing only on nonambulatory patients ages 12 and younger suggested even more dramatic improvements: At four years, this age group showed average improvements of 6.4 points on HFMSE and 4.5 points on RULM.
“At 48 months, over 90% of TOPAZ patients with nonambulatory SMA remained on apitegromab treatment on top of SMN therapy and we continued to observe sustained clinical benefit,” Backstrom said.
All who complete the TOPAZ or SAPPHIRE studies have the option of starting or continuing with apitegromab as part of an extension study called ONYX (NCT05626855), which is evaluating the therapy’s long-term safety and efficacy.
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