Omoprubart heading to pivotal stage of testing
Canbridge shares positive Phase 1/2 trial data of potential PNH therapy
Treatment with the experimental complement-blocking therapy omoprubart reduced markers of hemolysis, or blood cell destruction, in people with paroxysmal nocturnal hemoglobinuria (PNH).
Those findings, from preliminary data of a Phase 1/2 study, were announced by its developer, China-based Canbridge Pharmaceuticals, which now is planning to launch a pivotal trial to test the therapy.
“Based on the strength of these data, we plan to advance omoprubart to a pivotal trial in PNH in China and will meet shortly with the CDE to discuss our next steps,” James Xue, PhD, founder, chairman, and CEO of Canbridge, said in a press release.
Omoprubart, also known as CAN106, is an antibody-based therapy designed to block the activation of the complement cascade, a part of the immune system that drives hemolysis in PNH. The experimental therapy specifically targets a complement protein called C5.
The C5 protein also is targeted by AstraZeneca’s Soliris (eculizumab), which is currently the only complement-blocking medication available in China. After an initial set of infusions, given as a loading dose, Soliris is administered via an into-the-vein infusion every other week.
Canbridge is running an open-label Phase 1/2 study (NCT05539248) testing omoprubart in people with PNH who have not previously received complement-blocking therapy. The study enrolled a total of 16 patients, who were divided into three groups. All were treated with omoprubart, but with different dosing regiments.
The first group included four patients who received infusions of omoprubart at a dose of 12 mg/kg on day one, 16 mg/kg on day eight, and 20 mg/kg on day 15 and every four weeks thereafter. The four patients in group 2 were given 30 mg/kg of omoprubart on day one, 40 mg/kg on day eight and every four weeks thereafter.
All patients in these two groups have so far been followed for at least 26 weeks (about half a year). Preliminary data showed that treatment with omoprubart led to significant reductions in lactate dehydrogenase (LDH), a marker of hemolysis. LDH levels dropped by 49% in group 1 and by 73% in group 2. In both groups, mean levels of hemoglobin — the protein that red blood cells use to carry oxygen through the bloodstream — increased by about 2 g/dL.
For patients in group 1 who have been on omoprubart for at least one year, mean hemoglobin levels rose by 4 g/dL since the study’s start.
“We are particularly encouraged by the increased hemoglobin levels seen in the trial, which could decrease or eliminate blood transfusions, often used chronically in PNH patients, and reduce the burden on the healthcare system,” Xue said.
The third group included eight patients who were given 60 mg/kg of omoprubart on day one, then 80 mg/kg on day 15 and every eight weeks thereafter. Patients in this group have been followed for at least 13 weeks. Preliminary data showed that LDH levels decreased by 81%, while hemoglobin levels rose by a mean of 1 g/dL.
Pharmacological data indicated the therapy blocked C5 activation as designed, and safety data suggested it was generally well tolerated. All reported side effects were considered to be mild or moderate and resolved with time, and there were no serious safety problems reported.
Overall, omoprubart showed “comparable efficacy and safety” to Soliris, while requiring notably less frequent infusions, Xue said. “We look forward to further developing this first potentially long-acting PNH treatment in China, where patients do not have ready market access to anti-C5 antibody treatment.”
Xue said these positive data in PNH also “provide proof-of-concept for the use of omoprubart in additional indications, as complement blockade in PNH is a bellwether for other complement-mediated diseases.”