Scholar Rock announces final top-line results from Phase 1 SRK-015 trial
Scholar Rock announced final top-line results from the Phase 1 clinical trial of its product candidate, SRK-015, a highly specific inhibitor of myostatin activation, in healthy adult volunteers. Consistent with previously announced interim findings, the final results showed target engagement and no apparent safety signals were observed across all tested doses. Detailed results from the Phase 1 trial will be presented at the Cure SMA annual conference. In the single-ascending dose, or SAD, portion of the trial, adverse events, or AEs, were observed in 30% of SRK-015-treated subjects and 50 % of placebo-treated subjects. In the multiple-ascending dose, or MAD, portion of the trial, AEs were observed in 35% of SRK-015-treated subjects and 67% of placebo-treated subjects. There were no discontinuations due to a treatment-related AE, no hypersensitivity reactions and no deaths. A single serious AE of gallstone-induced pancreatitis was observed in an SRK-015-treated subject and was assessed by the trial investigator as unrelated to treatment. Immunogenicity as evaluated by anti-drug antibody testing was negative for all SRK-015 treated subjects in the trial. Target engagement was shown in the Phase 1 trial through increases from baseline in levels of latent myostatin. The levels of target engagement attained a plateau after a single dose of SRK-015 at 3 mg/kg or greater, suggesting target saturation. This plateau was sustained up to Day 84 after a single dose at 20 mg/kg. This durability of effect was further shown in the MAD portion of the trial, during which the plateau was sustained up to at least day 140 after three doses given once every two weeks at 20 mg/kg or 30 mg/kg. In contrast, no meaningful change was observed in the latent myostatin biomarker concentrations in subjects who received placebo. PD was evaluated through a proprietary, exploratory biomarker assay developed by Scholar Rock that measures serum concentrations of latent myostatin. This assay was used previously to measure target engagement in preclinical studies in healthy animals and a mouse model of SMA. Pharmacokinetic, or PK, data. Drug exposure to SRK-015 was dose-proportional and SRK-015's serum half-life was 23-33 days across dose cohorts. In these respects, SRK-015 displayed a PK profile consistent with what is commonly observed for monoclonal antibodies.