A new open-label phase 3 extension study (ACCESS-EXT) is set to evaluate the long-term safety, tolerability, and efficacy of pozelimab and cemdisiran combination therapy in patients with paroxysmal nocturnal hemoglobinuria (PNH).

The ACCESS-EXT trial is not yet recruiting but aims to enroll 300 participants who will receive subcutaneous pozelimab and cemdisiran every 4 weeks.

The study encompasses 2 treatment arms: PNH transition patients (PNH patients who completed treatment/protocol requirements [as applicable] in the parent studies [R3918-PNH-2021 {NCT05133531} or R3918-PNH-2022 {NCT05131204}]) and component 5 (C5) polymorphism patients (patients who were not treated in the parent studies but who present with a documented C5 polymorphism that renders them refractory to eculizumab/ravulizumab therapy).

Patients entering with a C5 polymorphism must have active disease and a lactate dehydrogenase (LDH) level of at least 2 times the upper limit of normal at the screening visit, and their PNH diagnosis must be confirmed by high-sensitivity flow cytometry testing.

Read more about PNH experimental therapies

The primary outcome measures of ACCESS-EXT are the incidence and severity of treatment-emergent serious adverse events, the incidence and severity of treatment-emergent adverse events of special interest, treatment-emergent adverse events leading to permanent treatment discontinuation, and the percent change in LDH level from baseline.

In addition, the trial aims to evaluate the long-term effects of pozelimab and cemdisiran combination therapy on measures of intravascular hemolysis, transfusion parameters, hemoglobin levels, fatigue, physical function, change in global health status, complement activation, serum concentration of total pozelimab, plasma concentrations of cemdisiran and total C5 protein, and immunogenicity of pozelimab and cemdisiran.

Patients who had significant protocol deviations in the parent study, developed any new condition, or experienced worsening of an existing condition that would compromise participation in the study will be excluded from the trial.

Moreover, the following exclusion criteria apply to participants entering with a C5 polymorphism: prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening (excludes prior eculizumab or ravulizumab); receipt of an organ transplant or a history of bone marrow transplantation or other hematologic transplant; no documentation of meningococcal vaccination within 5 years prior to enrollment; positive hepatitis B surface antigen or hepatitis C virus RNA during screening; known human immunodeficiency virus (HIV) with a history of opportunistic infections in the last year; known hereditary complement deficiency; and a documented history of active and uncontrolled systemic autoimmune disease, liver cirrhosis, or liver disease with evidence of impaired liver function.

The ACCESS-EXT trial is sponsored by Regeneron Pharmaceuticals.


A study to examine the long-term safety, tolerability, and effectiveness of pozelimab and cemdisiran combination therapy in adult patients with paroxysmal nocturnal hemoglobinuria (ACCESS-EXT). ClinicalTrials.gov. February 27, 2023. Accessed March 1, 2023.