Extension Period Findings Support Potential of Doublet Regimen in PNH

The combination of pozelimab, a monoclonal antibody targeting complement component C5, and cemdisiran, an N-acetylgalactosamine-conjugated small interfering RNA, was well tolerated and achieved long-term control of intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH) who switched from eculizumab in an open-label, single-arm, phase II study extension.

The study’s authors, led by Richard Kelly, MD, of the St. James University Hospital in Leeds, United Kingdom, noted that eculizumab and other complement component C5 inhibitors are typically administered intravenously, whereas pozelimab and cemdisiran are combined in a small volume subcutaneous maintenance regimen that can be self-administered.

Doublet PNH Therapy Maintains Response in Phase II Extension

The 52-week, open-label extension period enrolled all five patients who completed the initial 32-week treatment period, and all five completed the extension study. All participants were older adults with PNH that swapped from eculizumab maintenance to pozelimab 400 mg and cemdisiran 200 mg.

Over the extension period, no patients had breakthrough hemolysis or lactate dehydrogenase levels greater than 1.5-times the upper limit of normal, including two patients who swapped from higher doses of eculizumab.

The researchers reported that four out of five patients were transfusion-free, though one patient received a blood transfusion after being hospitalized for an acute complement-activating condition. The transfused patient experienced two serious and severe treatment-emergent adverse events, respiratory infection followed by acute hemolysis that did not meet the study’s breakthrough hemolysis criteria. Investigators judged these events were not related to the study treatment.

Overall, “findings support the ongoing development of pozelimab and cemdisiran combination therapy,” Dr. Kelly and colleagues suggested.

Reference

Kelly RJ, Houghton N, Munir T. 52-week open-label extension data from a phase 2 study evaluating the safety and efficacy of pozelimab and cemdisiran combination therapy in patients with paroxysmal nocturnal hemoglobinuria who switched from eculizumab. Abstract #2716. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.