Rare Daily Staff

Days after the U.S. Food and Drug Administration approved Apellis Pharmaceuticals’ Empaveli, the first and only targeted C3 therapy, for treatment of adults with paroxysmal nocturnal hemoglobinuria, Apellis and partner Swedish Orphan Biovitrum reported positive top-line results from the phase 3 PRINCE study evaluating the efficacy and safety of Empaveli in treatment naïve adults with PNH, meaning they had not received a complement inhibitor within three months before entering the study.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, life-threatening blood disorder caused by an acquired mutation, which leads to uncontrolled complement activation and the destruction of red blood cells through intravascular and extravascular hemolysis. According to a retrospective and a cross-sectional study of patients treated with C5 inhibitors, at least 72 percent had persistently low hemoglobin and at least 36 percent required one or more transfusions a year.

Results from the phase 3 PRINCE study in treatment naïve patients showed that Empaveli was statistically superior on the co-primary endpoints of hemoglobin stabilization and reduction in lactate dehydrogenase (LDH) compared to standard of care, which did not include complement inhibitors, at Week 26.

Eighty six percent of Empaveli-treated patients achieved hemoglobin stabilization compared to none of the patients on standard of care. Hemoglobin stabilization was defined as an avoidance of greater than 1 g/dL decrease in hemoglobin levels in the absence of transfusions.

Mean LDH in the Empaveli treated group decreased by 90 percent from baseline, which is within the normal range, compared to a 14 percent reduction on standard of care from baseline.

“The positive PRINCE data showed that Empaveli provided clinically meaningful improvements across multiple measures that are important for patients and build on our recent FDA approval of Empaveli in PNH,” said Federico Grossi, chief medical officer, Apellis. “Combined with previous studies, these results emphasize the potential of Empaveli to provide disease control for all adults with PNH regardless of prior treatment.”

EMPAVELI also achieved statistical superiority on several secondary endpoints, including improvements in hemoglobin levels and transfusion avoidance, compared to standard of care, which did not include complement inhibitors, as 91 percent of treated patients were transfusion free compared to 22% on standard of care.

The safety profile of Empaveli was consistent with previous studies.

“The PRINCE study results reinforce the efficacy and safety profile of Empaveli in PNH,” said Ravi Rao, head of research and development and chief medical officer at Sobi. “Our hope is to contribute to an improvement of care and to make a difference in the lives of people with this rare blood disease.”

Empaveli (pegcetacoplan) is the first and only approved therapy targeting C3, the central protein in the complement cascade. The drug acts proximally in the complement cascade controlling both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis. It carries a black box warning about serious infection caused by encapsulated bacteria and is available only through a restricted program under a REMS, in which prescribers must enroll in the program and must counsel patients about the risk of serious infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria.

Photo: Ravi Rao, head of research and development and chief medical officer at Sobi

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