Regeneron reports positive late-stage results for poze-cemdi in rare blood disorder PNH

Regeneron Pharmaceuticals has reported encouraging results from a phase 3 clinical trial assessing the efficacy of pozelimab combined with cemdisiran (referred to as poze-cemdi) for treating paroxysmal nocturnal haemoglobinuria (PNH), a rare blood disorder. The findings, derived from an exploratory cohort within the ACCESS-1 trial, were showcased at the American Society of Hematology (ASH) annual meeting.

PNH is an uncommon condition that affects approximately 1.5 individuals per million in the United States. It is characterized by a genetic mutation that causes the body's complement system to attack red blood cells, leading to various symptoms such as fatigue, shortness of breath, and potentially fatal blood clots.

Pozelimab is a fully human monoclonal antibody that inhibits the C5 protein, crucial for the activation of the complement system. Cemdisiran, on the other hand, is an investigational siRNA therapeutic designed to lower the levels of circulating C5.

The data from the ACCESS-1 trial revealed that 96% of patients treated with poze-cemdi achieved adequate control of lactate dehydrogenase (LDH)—a biomarker used to gauge the extent of haemolysis—across study visits ranging from week eight to 26. In contrast, 80% of patients receiving AstraZeneca’s standard C5 inhibitor, ravulizumab (Ultomiris), achieved the same control. Moreover, 93% of patients in the poze-cemdi group reached LDH normalization on average, compared to 65% in the ravulizumab group. The trial also showed an 84% reduction in LDH levels from baseline in the poze-cemdi group, compared to a 74% reduction in the ravulizumab group.

After completing the 26-week ACCESS-1 trial, participants had the option to continue into an open-label extension trial (OLE) and receive poze-cemdi. At the beginning of the OLE, 68% of patients treated with ravulizumab had adequate LDH control, which increased to 95% after switching to poze-cemdi. This included four out of five patients who had not achieved LDH control while on ravulizumab.

In addition to the exploratory cohort, a separate registrational cohort is investigating poze-cemdi compared to another AstraZeneca C5 inhibitor, Soliris (eculizumab).

Christopher Patriquin, an investigator in the ACCESS-1 trial from the University of Toronto and University Health Network, commented on the findings, noting that the combination of pozelimab and cemdisiran provided comprehensive, rapid, and sustained inhibition of the terminal complement system throughout the dosing interval. He expressed optimism that if results from the registrational cohort are consistent, the combination could significantly improve treatment outcomes for many PNH patients.