Jun Ho Jang, MD, PhD, Professor, Division of Hematology-Oncology at Samsung Medical Center, discusses results from an open-label extension study testing pozelimab plus cemdisiran combination therapy in patients with paroxysmal nocturnal hemoglobinuria (PNH), who previously received the combination therapy or received ravulizumab.
PNH is an acquired disorder that leads to the premature death and impaired production of blood cells. It can occur at any age, but is usually diagnosed in young adulthood. People with PNH have recurring episodes of symptoms due to hemolysis, which may be triggered by stresses on the body such as infections or physical exertion. This results in a deficiency of various types of blood cells and can cause signs and symptoms such as fatigue, weakness, abnormally pale skin, shortness of breath, and an increased heart rate. People with PNH may also be prone to infections and thrombosis or hemorrhage, and are at increased risk of developing leukemia. It is caused by acquired, rather than inherited, genetic changes in the PIGA gene.
Recently, data was presented at the 2025 American Society of Hematology (ASH) meeting on the safety and efficacy of pozelimab plus cemdisiran versus ravulizumab in patients with PNH. Pozelimab is a monoclonal antibody that inhibits C5 activation, and cemdisiran is a silencing RNA that reduces circulating C5; the combination of pozelimab and cemdisiran is being investigated for its ability to achieve complete, durable inhibition of C5.
The data presented was derived from an exploratory arm of a follow-in open-label extension study (NCT05744921) where patients who received pozelimab plus cemdisiran in the parent study continued on the combination therapy (legacy-combo) and patients who received ravulizumab in the parent study were switched to the combination therapy (legacy-rav).
A total of 44 patients enrolled in the study, 19 legacy-combo and 22 legacy-rav, and received treatment until week 36. At week 36, mean percent change from baseline in lactate dehydrogenase (LDH) was 6.4 for patients who received legacy-combo and -19.7 for patients who received legacy-rav. Following the first dose of combo in this study, 21 of 22 patients in each arm maintained adequate control of LDH, including 3 patients in the legacy-rav arm who had not achieved adequate control of hemolysis in the first transition visit of the parent study.
All patients who received legacy-rav achieved and maintained CH50 levels of 0 U/mL from baseline to week 24, a mean change from baseline of -15 U/mL. 61.4% of patients achieved TA, defined as not requiring a red blood cell transfusion based on post-baseline hemoglobin values, at week 36.
Breakthrough hemolysis was experienced by one patient in each arm, both associated with a complement-activating condition. 16 and 17 patients experienced an extension-emergent adverse event in the legacy-combo and legacy-rav arms, respectively. The most common adverse event was headache. Serious treatment-emergent adverse events were experienced by 2 and 3 patients in the legacy-combo and legacy-rav arms, respectively. There were no adverse events leading to permanent study discontinuation or death.
For more information, click here.
To learn more about PNH and other rare hematologic conditions, visit https://checkrare.com/diseases/hematologic-disorders/