Regeneron announces Phase 3 data of exploratory cohort from ACCESS-1 trial

Regeneron (REGN) Pharmaceuticals announced updated Phase 3 data of an exploratory cohort from the ACCESS-1 trial investigating its first-in-class pozelimab and cemdisiran combination treatment against ravulizumab, a standard-of-care complement factor 5 inhibitor, in patients with paroxysmal nocturnal hemoglobinuria. Results were shared during an oral session at the American Society of Hematology 2024 Annual Meeting and support continued development of poze-cemdi in PNH, including in a separate registrational cohort, as well as in other complement-mediated diseases. Poze-Cemdi is a first-in-class combination of an antibody and an siRNA targeting C5: pozelimab is a fully human monoclonal antibody designed to block the activity of C5, while cemdisiran is an investigational siRNA therapeutic that reduces circulating levels of C5. Patients were naive to complement inhibition, with the primary endpoint of Cohort A being percent change in LDH at 26 weeks. In Cohort A, patients were randomized to receive either poze-cemdi or ravulizumab. The ravulizumab arm generally responded as would be expected based on historical clinical trial data, which indicate that 44% of treated patients did not achieve LDH normalization. Results for those treated with poze-cemdi, compared to ravulizumab, were as follows: 96% achieved adequate LDH control across study visits on average with poze-cemdi, compared to 80% with ravulizumab; 93% achieved LDH normalization across study visitson average with poze-cemdi, compared to 65% with ravulizumab; 84% decrease in LDH from baseline at week 26 with poze-cemdi compared to 74% with ravulizumab; The CH50 profile observed with poze-cemdi demonstrated complete and uninterrupted inhibition of terminal complement, compared to the profile for ravulizumab showing loss of inhibition at the end of the dosing interval; After week 26, all patients who completed ACCESS-1 could enroll in a follow-on OLE trial and receive poze-cemdi, including those who initially received ravulizumab. At the start of the OLE, 68% of patients treated with ravulizumab had adequate LDH control. After switching to poze-cemdi, 95% of patients achieved LDH control. This included 4 of 5 patients who had failed to achieve LDH control while on ravulizumab. The safety profile of poze-cemdi was generally consistent with approved C5 inhibitors. Serious adverse events occurred in two patients receiving poze-cemdi that were considered unrelated to treatment by the investigator. This included one patient who had post-traumatic cellulitis that resolved with treatment while continuing poze-cemdi. The second patient experienced a fever, seizure and hemolytic crisis within one week of the first dose of the combination that also resolved while continuing poze-cemdi; the patient later had a fatal SAE of sepsis and disseminated intravascular coagulation on day 130. In the OLE, among patients who switched to poze-cemdi from ravulizumab, 68% experienced TEAEs, with the most common being non-serious, mild to moderate injection-site reactions. There were also no fatal TEAEs, and no patients discontinued therapy due to an adverse event.