Benzinga | Apr 6, 2021 07:02AM EDT

Scholar Rock Announces 12-Month Top-Line Results From TOPAZ Phase 2 Clinical Trial Evaluating Apitegromab In Patients With Type 2 And Type 3 Spinal Muscular Atrophy

Scholar Rock (NASDAQ:SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, today announced positive top-line data from the TOPAZ Phase 2 clinical trial evaluating apitegromab (SRK-015) in patients with Type 2 and Type 3 spinal muscular atrophy (SMA).

"These top-line 12-month data provide further support towards establishing apitegromab as a potential first muscle-directed therapy for patients with SMA," said Yung Chyung, M.D., Chief Medical Officer of Scholar Rock. "The findings also offer important insights into myostatin biology and our scientific approach of targeting the latent forms of growth factors. We look forward to advancing the development and investigation of apitegromab as we plan to initiate a pivotal trial in SMA by the end of 2021 and explore its potential in additional disease areas."

Key findings from the 12-month top-line analysis include:

* Cohort 1: 5-21 years of age, ambulatory Type 3, 20 mg/kg dose monotherapy and in conjunction with nusinersen: Observed a mean change from baseline in Revised Hammersmith Scale (RHS) of a 0.3-point decline. Majority of patients across the cohort (57%, 13/23 of patients) maintained or improved their motor function, as reflected by a >0-point change from baseline in RHS score, and 22% of patients (5/23) attained a >3-point increase from baseline. Results suggest potential clinical effect in certain patients in this population. Cohort 2: 5-21 years of age, Type 2 and non-ambulatory Type 3 who initiated nusinersen ?5 years old, 20 mg/kg dose: Observed a mean change from baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) of a 0.6-point improvement. Majority of patients (64%, 9/14 of patients) attained a >1-point increase from baseline and 29% of patients (4/14) attained a >3-point increase from baseline. Results support the potential durability of the improvements in motor function observed at the six-month interim analysis. Cohort 3: ?2 years of age, Type 2 who initiated nusinersen <5 years of age: Observed a mean change from baseline in HFMSE of 7.1-point and 5.3-point improvements in the 20 mg/kg dose and the 2 mg/kg dose arms, respectively. Across the full cohort, 59% of patients (10/17) attained a >5-point increase and 35% of patients (6/17) attained a >10-point increase from baseline. Results demonstrate further improvements in motor function beyond what had been observed at the six-month interim analysis. Dose response continued to be observed based upon clinical efficacy (HFMSE improvements) and pharmacodynamics (target engagement). No safety signals for apitegromab were identified as of the 12-month top-line analysis. The five most frequently reported treatment-emergent adverse events (TEAEs) were headache, pyrexia, upper respiratory tract infection, cough, and nasopharyngitis. All 57 patients who completed the 12-month TOPAZ trial have opted into the extension period. "These 12-month results from the Phase 2 apitegromab TOPAZ trial have built upon the previously announced exciting 6-month interim results," said Thomas Crawford, M.D., Professor of Neurology at the Johns Hopkins School of Medicine and Lead Investigator of the TOPAZ trial. "There looks to be promising potential for a muscle-directed therapy that will complement the unmet need still evident, and likely emerging, in many individuals with SMA who receive SMN-enhancing therapies. Though much work remains to be done, I believe the results are wonderful news for the SMA community, and I am enthusiastic about the potential that apitegromab may offer for further meaningful functional improvements." Detailed summary of the TOPAZ 12-month top-line results by cohort Apitegromab is a selective inhibitor of the activation of latent myostatin. The TOPAZ Phase 2 proof-of-concept trial enrolled 58 patients with Type 2 and Type 3 SMA across 16 study sites in the United States and Europe. The trial evaluated the safety and efficacy of intravenous apitegromab dosed every four weeks (Q4W) over a 12-month treatment period. Four patients (one in Cohort 2 and three in Cohort 3) each missed three consecutive doses of apitegromab over the course of the 12-month treatment period due to COVID-19-related site access restrictions and are excluded from the prespecified intent-to-treat primary analysis. Cohort 1: This open-label, single-arm cohort enrolled 23 patients with ambulatory Type 3 SMA. Patients were treated with 20 mg/kg of apitegromab either as a monotherapy or in conjunction with an approved SMN upregulator therapy (nusinersen).The primary objectives of Cohort 1 were to assess safety and the mean change from baseline in RHS following 12 months of treatment. In Cohort 1 (pooled population), the mean change from baseline in RHS score was a 0.3-point decline. The Cohort 1 efficacy data suggest a potential clinical effect of apitegromab in certain patients in this population, as 57% of patients observed a maintenance or improvement in RHS score (>0-point change from baseline) and 22% of patients achieved at least a 3-point increase in RHS score from baseline.