Zilucoplan (RA101495 SC)

Zilucoplan (RA101495 SC) is being developed for convenient self-administered subcutaneous injection for the treatment of paroxysmal nocturnal hemoglobinuria, or PNH. PNH is a rare, chronic life-threatening blood disorder where red blood cells are mistakenly attacked and destroyed by the complement system. Ra Pharma® is currently advancing zilucoplan into a Phase 2 clinical program in PNH patients. The Company is also developing zilucoplan, administered SC, to treat other debilitating complement-mediated diseases such as generalized myasthenia gravis, or gMG, and lupus nephritis, or LN.

Binding Sites

Inhibition of C5 is a clinically validated target for the control and suppression of complement-induced hemolysis in patients with PNH. Currently the only drug approved to treat PNH is eculizumab (Soliris), a humanized monoclonal antibody that acts as a C5 inhibitor and is administered biweekly by intravenous, or IV, infusion by healthcare professionals. However, loss of hemolysis control, or breakthrough hemolysis, has been observed in patients treated with eculizumab, particularly towards the end of its two-week administration cycle.

Ra Pharma believes zilucoplan, when self-administered SC on a more frequent basis, may provide sustained and improved disease control, reducing the risk of breakthrough hemolysis, and offering PNH patients more convenience and flexibility compared with eculizumab.

Zilucoplan has been studied in a Phase 1 randomized, double-blind, placebo controlled clinical trial in healthy volunteers to assess the safety, tolerability, pharmacokinetics, or PK, and pharmacodynamics, or PD, of zilucoplan following single and multiple dose SC administration. The results from this trial, which were presented at the European Hematology Association meeting in 2016, demonstrated, as compared to placebo:

  • highly predictable, dose dependent PK after single and multiple dose SC injections;
  • near-complete suppression of ex vivo hemolysis and complement activity after a single SC dose;
  • maintenance of robust ex vivo hemolysis suppression and complement inhibition with daily SC dosing; and
  • an acceptable safety and tolerability profile with no serious adverse events reported.

Ra Pharma’s global Phase 2 program, consisting of two Phase 2 trials, is designed to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of zilucoplan in patients with PNH, including eculizumab-naïve patients, eculizumab-switch patients, and eculizumab-inadequate responders.