Scholar Rock Reports Preliminary Pharmacokinetic and Pharmacodynamic Data from TOPAZ Phase 2 Trial of SRK-015 for the Treatment of SMA

25 November 2019

Scholar Rock announced preliminary pharmacokinetic (the effect the body has on the drug) and pharmacodynamic (the effect the drug has on the body) results from the TOPAZ Phase 2 trial of SRK-015 for the treatment of patients with SMA. 

SRK-015 is an experimental therapy directed at the muscle, that aims to reverse or restrict the atrophy and weakness experienced by SMA patients. SRK-015 works by specifically inhibiting an important protein called myostatin, which can restrict the growth and function of muscles. By targeting myostatin, SRK-015 can potentially release the breaks on muscle cell growth leading to an increase in muscle size and function.

SRK-015 is now in a Phase 2 trial called TOPAZ, which is evaluating the safety and efficacy of SRK-015, dosed intravenously every four weeks over a 12-month treatment period.  The trial is anticipated to enrol approximately 55 patients with SMA Type 2 or Type 3 in Europe and the U.S. across three distinct cohorts:

  • Cohorts 1 & 2: Patients treated with 20 mg/kg of SRK-015
  • Cohort 3: Patients randomised to either 20 mg/kg or 2 mg/kg

The primary objectives of the cohorts are to assess safety and measure motor function through clinically meaningful outcome measures validated in SMA, such as the Hammersmith Functional Motor Scale Expanded (HFMSE) in non-ambulatory SMA and the Revised Hammersmith Scale (RHS) in ambulatory SMA.

The preliminary pharmacokinetic and pharmacodynamic analysis of the TOPAZ trial includes data from 29 patients across the three cohorts. These patients had received one dose of SRK-015 and were evaluated for four weeks as of the data cut-off.

The preliminary results demonstrated:

  • Presence of latent myostatin in patients with SMA, further supporting the relevance of this drug target in SMA
  • Robust and dose-dependent engagement between SRK-015 and latent myostatin
  • No clinically significant safety signals had been observed as of the data cut-off for this preliminary analysis.
  • An interim efficacy and safety analysis is planned on a subset of patients with at least six months of treatment exposure. These interim results are expected in the first half of 2020.

Further information:

The press release

More about the trials: