RA Pharmaceuticals says Phase 2 trial of zilucoplan meets primary endpoint

Ra Pharmaceuticals announced positive top-line results from the Company’s Phase 2 clinical trial evaluating zilucoplan for the treatment of generalized myasthenia gravis, achieving clinically meaningful and statistically significant reductions in both the primary and key secondary endpoints for both zilucoplan dose groups tested versus placebo at 12 weeks. Zilucoplan dosed at 0.3 mg/kg subcutaneously daily achieved a mean reduction from baseline of 6.0 points in the Quantitative Myasthenia Gravis score and a mean reduction from baseline of 3.4 points in the MG Activities of Daily Living score, with no patients treated with the 0.3 mg/kg dose of zilucoplan requiring rescue therapy. The Phase 2, multi-center, randomized, double-blind, placebo-controlled trial was designed to evaluate the safety, tolerability, and preliminary efficacy of zilucoplan in patients with gMG, regardless of prior therapies, who had a MGFA Disease Class of II-IVa at screening and a QMG score, a physician-administered assessment of MG-related muscle weakness, of greater than or equal to 12 at screening and randomization. The trial enrolled 44 patients in the U.S. and Canada. At the outset of the 12-week treatment period, patients were randomized in a 1:1:1 ratio to receive daily, SC doses of 0.1 mg/kg of zilucoplan, 0.3 mg/kg of zilucoplan, or matching placebo. The pre-specified primary efficacy endpoint was the change in QMG score from baseline to week 12. The key secondary efficacy endpoint was the change in MG-ADL score, a patient-reported outcome measure, from baseline to week 12. Significance testing was pre-specified at a 1-sided alpha of 0.1. All 44 patients completed the 12-week study and, of these, 43 elected to enter a long-term extension to receive active study drug. The pre-specified primary efficacy endpoint of change from baseline to Week 12 in QMG score was met with zilucoplan dosed at 0.3 mg/kg SC daily, resulting in a clinically meaningful and statistically significant improvement over placebo.The key secondary efficacy endpoint of change from baseline to Week 12 in the MG-ADL score was met with zilucoplan dosed at 0.3 mg/kg SC daily, resulting in a clinically meaningful and statistically significant improvement over placebo. QMG and MG-ADL outcomes for the 0.1 mg/kg SC daily dose were similar to but less pronounced than the 0.3 mg/kg SC daily dose, also achieving pre-specified statistical significance on both endpoints. The threshold for statistical significance used in pivotal Phase 3 studies was achieved in a pre-specified analysis of the pooled active arms versus placebo, which showed a placebo-corrected change in MG-ADL at Week 12 = -2.2. Rescue therapy with intravenous immunoglobulin or plasma exchange was required by 3/15 patients in the placebo arm, 1/15 patients in the 0.1 mg/kg zilucoplan arm, and in zero patients in the 0.3 mg/kg zilucoplan arm. Treatment with zilucoplan had a favorable safety and tolerability profile in the study, consistent with previously-completed Phase 1 and Phase 2 studies. The majority of adverse events reported were mild and were not considered by the investigators to be related to study drug. There were no serious AEs observed related to treatment with zilucoplan. Based on these data, Ra Pharma plans to engage with regulatory agencies, including the U.S. Food and Drug Administration, in the first half of 2019 regarding the design of a Phase 3 clinical trial evaluating the 0.3 mg/kg dose of zilucoplan versus placebo in patients with gMG.
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