RA Pharmaceuticals announces gMG phase 2, long-term data at AAN meeting
Ra Pharmaceuticals announced the presentation of data from the Company's Phase 2 clinical trial evaluating zilucoplan for the treatment of generalized myasthenia gravis , including data from the open-label, long-term extension study, at the 2019 American Academy of Neurology Annual Meeting, in Philadelphia, PA, from May 4-10, 2019. The 0.3 mg/kg dose of zilucoplan consistently achieved rapid, sustained, and near-complete complement inhibition. The 0.1 mg/kg dose of zilucoplan achieved rapid, sustained, but sub-maximal complement inhibition. Based on the pharmacokinetic, pharmacodynamic, and efficacy results, the 0.3 mg/kg dose of zilucoplan was selected for evaluation in the upcoming pivotal Phase 3 trial. As previously reported, the pre-specified primary efficacy endpoint of change from baseline to week 12 in Quantitative Myasthenia Gravis 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 Activities of Daily Living 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 0.3 mg/kg dose of zilucoplan led to rapid, statistically significant, and clinically meaningful reductions in additional pre-specified secondary endpoints, the MG Composite and the 15-item MG Quality of Life revised scale, versus placebo at week 12. 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. Sustained responses were observed for all four efficacy endpoints after 24 weeks at the 0.3 mg/kg dose of zilucoplan. Placebo subjects crossing over to the 0.3 mg/kg dose of zilucoplan after 12 weeks experienced rapid, clinically meaningful, and statistically significant improvements for all four efficacy endpoints from weeks 12 to 24, with changes from week 12 to week 24. Based on feedback provided by the U.S. Food and Drug Administration, Ra Pharma plans to initiate a single, 12-week, pivotal, Phase 3, randomized, double-blind, placebo-controlled trial evaluating the efficacy of a once-daily, SC self-administered dose of 0.3 mg/kg of zilucoplan versus placebo. The trial is expected to enroll approximately 130 patients with gMG who are acetylcholine receptor-antibody-positive, regardless of their prior therapies. The primary endpoint will be the change in the MG-ADL score from baseline to week 12. Following completion of the Phase 3 clinical trial, patients will have the option to enroll into an open-label, long-term extension study.