Zilucoplan

Ra Pharmaceuticals is developing zilucoplan for generalized myasthenia gravis (gMG), immune-mediated necrotizing myopathy (IMNM), and other tissue-based complement-mediated disorders with high unmet medical need. The product is designed for convenient, subcutaneous (SC) self-administration.

Zilucoplan is a synthetic, macrocyclic peptide discovered using Ra Pharmaceuticals’ 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 Pharmaceuticals announced the successful completion of the Phase 2 clinical trial evaluating zilucoplan for the treatment of gMG, achieving rapid, clinically meaningful, and statistically significant reductions in pre-specified primary and key secondary endpoints for both zilucoplan dose groups tested versus placebo at 12 weeks. In May 2019, Ra Pharmaceuticals presented data Phase 2 open-label long-term extension study, where sustained responses were observed for all four efficacy endpoints after 24 weeks at the 0.3 mg/kg dose of zilucoplan. Placebo patients 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. Treatment with zilucoplan had a favorable safety and tolerability profile in the study, and there were no serious adverse events observed related to treatment with zilucoplan.

In May 2019, Ra Pharmaceuticals reported positive results from the Phase 1 ethno-bridging study in healthy subjects of Japanese and non-Japanese descent, showing that the pharmacokinetic and pharmacodynamic profile of zilucoplan was consistent and similar across both groups. These results support development of zilucoplan for the Japanese market without the need for dose modification.

In September 2018, Ra Pharmaceuticals reported positive results from the Phase 1b, multi-center, open-label, pharmacokinetic 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.

In April 2019, Ra Pharmaceuticals presented pre-clinical data for the poly(D,L-lactic-co-glycolic acid) (PLGA) extended release (XR) formulation of zilucoplan. Weekly SC doses of the PLGA XR formulation of zilucoplan in non-human primates rapidly achieved and maintained target drug concentrations for 14 days, sustaining near complete pharmacodynamic inhibition throughout this period.