**Regeneron Pharmaceuticals has shared positive data from a phase 3 trial of pozelimab plus cemdisiran (poze-cemdi) in patients with the rare blood disorder paroxysmal nocturnal haemoglobinuria (PNH).**
Results from an exploratory cohort of the ACCESS-1 trial were presented at this year’s American Society of Hematology (ASH) annual meeting and support the continued development of the combination treatment in PNH and other complement-mediated diseases, Regeneron said.
Affecting up to 1.5 people per million in the US, PNH is caused by a genetic mutation that results in the body’s complement system attacking its red blood cells. Patients can experience a range of symptoms, including fatigue, shortness of breath and life-threatening blood clots.
Pozelimab is a fully human monoclonal antibody designed to block the activity of the C5 protein, which is involved in complement system activation, while cemdisiran is an investigational siRNA therapeutic that reduces circulating levels of C5.
Data from ACCESS-1 showed that 96% of poze-cemdi-treated patients achieved adequate lactate dehydrogenase (LDH), a biomarker used to measure the degree of haemolysis, control across study visits (weeks eight to 26) on average, compared to 80% of those randomised to receive AstraZeneca’s standard-of-care C5 inhibitor ravulizumab, marketed under the brand name Ultomiris.
Of the patients in the poze-cemdi group, 93% achieved LDH normalisation across study visits on average, compared to 65% of those in the ravulizumab arm, and an 84% decrease in LDH from baseline was observed for Regeneron’s combination compared to 74% with ravulizumab.
After 26 weeks, all patients who completed ACCESS-1 could enrol in a follow-on open label extension trial (OLE) and receive poze-cemdi. At the start of the OLE, 68% of patients treated with ravulizumab had adequate LDH control, with this rising to 95% after switching to poze-cemdi, including four of five patients who had failed to achieve LDH control while on ravulizumab.
A separate registrational cohort investigating poze-cemdi against another of AstraZeneca’s C5 inhibitors Soliris (eculizumab) is ongoing.
ACCESS-1 trial investigator, Christopher Patriquin, University of Toronto and University Health Network, said: “In this phase 3 exploratory cohort, the complementary mechanisms of pozelimab and cemdisiran enabled complete, rapid, uninterrupted and durable inhibition of terminal complement throughout the dosing interval.”
“This data validates this novel combination approach, and we look forward to results from the registrational cohort, which if repeated, could help transform what may be possible for many people with PNH,” he added.