Ra Pharma® is developing zilucoplan for generalized myasthenia gravis (gMG) and other complement-mediated disorders with high unmet medical need. The product is designed for convenient, once-daily subcutaneous self-administration.

Zilucoplan is a synthetic, macrocyclic peptide discovered using Ra Pharma’s powerful proprietary drug discovery technology. The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.


In December 2018, Ra Pharma announced positive top-line results from the Company’s Phase 2 clinical trial evaluating zilucoplan for the treatment of gMG. 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. The trial enrolled a total of 44 patients. 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 primary efficacy endpoint was the change in QMG score, a physician-administered assessment of MG-related muscle weakness, from baseline to week 12. The key secondary efficacy endpoint was the change in MG Activities of Daily Living, or 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. Zilucoplan achieved clinically meaningful and statistically significant reductions in both the primary and key secondary endpoints at both dosage levels. At week 12, zilucoplan dosed at 0.3 mg/kg SC daily achieved a mean reduction from baseline of 6.0 points in the QMG score (placebo-corrected change = -2.8; p=0.05) and a mean reduction from baseline of 3.4 points in the MG-ADL score (placebo-corrected change = -2.3; p=0.04), in each case resulting in a clinically meaningful and statistically significant improvement over placebo.

In February 2018, Ra Pharma announced data from the Company’s global Phase 2 program in PNH, in which zilucoplan achieved consistent, sustained, and near-complete inhibition of C5. In treatment-naïve patients, zilucoplan met the primary endpoint, demonstrating a rapid, robust, and sustained reduction in lactate dehydrogenase (LDH) from baseline to the mean of weeks 6-12 and near-complete suppression of complement activity. In transfusion-independent eculizumab switch patients, patients were maintained an overall stable mean LDH level, with one patient withdrawing early due to breakthrough hemolysis and reverting to eculizumab without complications.

In September 2018, Ra Pharma reported positive results from the Phase 1b, multi-center, open-label, pharmacokinetic (PK) study of zilucoplan in patients with renal disease. The trial enrolled 16 patients, eight with severe renal impairment matched with eight healthy control subjects. The PK profile of zilucoplan was consistent across both groups, with exposures similar in renally-impaired patients and healthy volunteers. These results support the expansion of zilucoplan into complement-mediated renal disorders without the need for dose adjustment.