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The purpose of SMA Europe is to provide a framework to stimulate collaboration and accelerate translational research pathways in SMA and promote patient care.

  1. Scholar Rock announces results from TOPAZ phase 2 trial in Type 2 and 3 SMA

    Scholar Rock announces results from TOPAZ phase 2 trial in Type 2 and 3 SMAWhat is apitegromab?

    Apitegromab (SRK-015) is a muscle-directed therapy that aims to reverse or restrict the muscle atrophy and weakness experienced by people living with SMA. The drug is an antibody that very specifically targets an important protein called myostatin, which restricts muscle mass and strength. Scholar Rock believes that by preventing the activation of myostatin, a clinically meaningful increase in muscle mass and strength will be achieved.

    The European Medicines Agency (EMA) granted apitegromab Priority Medicines (PRIME) designation, recognising unmet medical needs of people living with SMA.

    What is TOPAZ?

    Topaz is a clinical trial which assesses the safety and efficacy of apitegromab in people living with Type 2 and Type 3 SMA. Enrolment was completed in January 2020 and the 12 month data announced by Scholar Rock yesterday, demonstrate proof-of-concept for its therapeutic potential.

    What were the key findings from this 12-month top-line analysis?

    • Cohort 1: 23 Individuals aged 5 to 21 with ambulatory Type 3 SMA were given 20 mg/kg of apitegromab every four weeks as a monotherapy, or in conjunction with nusinersen:
      • A mean change from baseline in motor function tests (Revised Hammersmith Scale (RHS)) of a 0.3-point decline was observed.
      • The majority of patients across the cohort maintained or improved their motor function, as reflected by a >0-point change from baseline in RHS score and 22% of patients attained a >3-point increase from baseline.
      • These results suggest a potential clinical effect in certain people in this population.
    • Cohort 2: 14 individuals aged 5 to 21 with Type 2 and non-ambulatory Type 3 who had started nusinersen treatment at the age of 5 years or older, were given 20 mg/kg of apitegromab every four weeks.
      • A mean change from baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) of a 0.6-point improvement was observed.
      • The majority of patients (64%) attained a >1-point increase from baseline and 29% of patients attained a >3-point increase from baseline.
      • These results support the potential durability of the improvements in motor function observed at the six-month interim analysis.
    • Cohort 3: 17 children aged 2 years or older with Type 2 SMA who had started treatment with nusinersen before age 5 years were given two doses of apitegromab (20 mg/kg and 2 mg/kg) in conjunction with nusinersen:
      • 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, were observed.
      • Across the full cohort, 59% of patients attained a >5-point increase and 35% of patients attained a >10-point increase from baseline.
      • These results demonstrate further improvements in motor function beyond what had been observed at the six-month interim analysis.
      • A dose response continued to be observed based upon clinical efficacy (HFMSE improvements) and pharmacodynamics (target engagement).
    • Safety: The five most frequently reported treatment-emergent adverse events were headache, pyrexia, upper respiratory tract infection, cough, and nasopharyngitis. As of these 12-month top-line results, no safety signals for apitegromab have been identified.

    What next?

    Based on these results, a phase 3 trial initiation is expected by the end of 2021.

    More information