Regeneron (REGN) Completes Enrollment in Phase 3 ACCESS-1 Trial of PNH Combination Therapy 'Pozelimab/Cemdisiran' and Aims for Data Readout Later This Year
A New Paradigm to Overcome the Limitations of Existing C5 Inhibitors
Current standard treatments for Paroxysmal Nocturnal Hemoglobinuria (PNH), such as eculizumab and ravulizumab (C5 inhibitors), have limitations in adequately controlling intravascular hemolysis in some patients. Regeneron's Phase 3 ACCESS-1 trial specifically targets this refractory patient population, focusing on demonstrating the synergistic effect of a combination therapy. By combining two drugs with different mechanisms of action, the trial aims to address the incomplete C5 inhibition observed with single-agent therapy, garnering significant attention from the scientific and market communities.
'Dual C5 Inhibition' Synergy Mechanism of siRNA and Monoclonal Antibody
This combination therapy involves administering cemdisiran, an siRNA therapeutic that inhibits the production of C5 protein, and pozelimab, a human monoclonal antibody (mAb) that directly binds to and neutralizes circulating C5 protein. Cemdisiran fundamentally blocks the synthesis of C5 protein in the liver, while pozelimab binds to and completely neutralizes the remaining C5 protein in the circulation. This dual C5 inhibition mechanism is considered an innovative therapeutic approach that can induce more potent and sustained C5 inhibition compared to single-agent antibody therapy.
Superior Hemolysis Inhibition Effect Compared to the Control Drug Demonstrated in the Exploratory Cohort
According to the recently released data from the ACCESS-1 exploratory cohort, the combination therapy of pozelimab and cemdisiran demonstrated superior lactate dehydrogenase (LDH) level control compared to ravulizumab. In particular, the significant reduction in hemolysis observed in patients who switched to this combination therapy after failing to achieve LDH control with ravulizumab is a clinically significant achievement. This suggests that the combination therapy may offer a potential alternative for patients with severe PNH who are exposed to chronic anemia and the risk of thrombosis due to lack of response to standard treatments.
Patient Enrollment Completed in the Registration Cohort and Data Readout Expected by the End of 2026
Regeneron announced that patient enrollment and registration for the ACCESS-1 registration cohort, which uses eculizumab as a control, were successfully completed in April 2026. The company plans to obtain the data readout for the registration cohort, which will serve as the basis for FDA approval, and submit it to regulatory authorities by the end of 2026. The success of this trial will be a critical commercial milestone for Regeneron, determining whether it can enter the next-generation complement therapy market and reshape the area currently dominated by AstraZeneca.
Strengthening Regeneron's Rare Disease Portfolio Through Securing Exclusive Rights
In addition, in June 2024, Regeneron fully amended and restated the C5 license agreement with Alnylam Pharmaceuticals (ALNY), securing global exclusive rights to both cemdisiran monotherapy and combination therapy. This rights acquisition, with an upfront payment of $10 million, allows Regeneron to reduce its dependence on external partnerships and strengthen its independent pipeline for the development and commercialization of rare disease therapies. As a result, the combination of pozelimab and cemdisiran will be a key growth driver for Regeneron, establishing a long-term and independent revenue model in the high-value complement-mediated disease area.
The global PNH treatment market is estimated at $4.6 to $5 billion as of 2025, dominated by AstraZeneca's (AZN) Ultomiris (ravulizumab) and Soliris (eculizumab). The combination therapy of pozelimab and cemdisiran is demonstrating strong Phase 3 clinical data, positioning it to move beyond a niche market and potentially become a mainstream treatment by targeting patients who are refractory to existing C5 inhibitors. In the short term, the Phase 3 registration trial data, expected to be released in late 2026, will be a key catalyst for determining the value of Regeneron's (REGN) rare disease pipeline. In the medium to long term, if the dual C5 inhibition mechanism (siRNA and monoclonal antibody combination) is proven, it could transform the treatment paradigm for complement-mediated diseases and establish a superior clinical position compared to competitors. The acquisition of global exclusive rights to cemdisiran from Alnylam (ALNY) in June 2024 is expected to significantly contribute to maximizing Regeneron's margins and securing independent market dominance in the commercialization phase.
Source: ClinicalTrials.gov (api_ct)