RARE Daily

Apellis Releases New Data Demonstrating Superiority of Its Experimental PNH Drug to Soliris

June 15, 2020

Rare Daily Staff

Apellis Pharmaceuticals presented positive new data from the pivotal phase 3 study of its experimental targeted therapy pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria that showed it beat Alexion’s Soliris in several measures. 

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, life-threatening blood disorder associated with abnormally low hemoglobin levels due to the destruction of oxygen-carrying red blood cells, or hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue and difficulty breathing.

Pegcetacoplan is an experimental, targeted C3 inhibitor designed to regulate excessive complement activation, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b. Apellis is evaluating pegcetacoplan in several clinical studies including PNH, geographic atrophy (GA), and C3 glomerulopathy. Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of PNH and the treatment of GA.

The PEGASUS study is a multi-center, randomized, open-label, active-comparator controlled phase 3 study in 80 adults with PNH. The primary objective of this study was to establish the efficacy and safety of pegcetacoplan compared to eculizumab.

Apellis released detailed results from the study in January that showed that pegcetacoplan was superior to the currently approved therapy eculizumab (Soliris) in increasing levels of hemoglobin by a mean adjusted level of 3.8 g/dL at week 16, 53 percent higher than the eculizumab arm.

At that time the company noted retrospective studies that showed approximately 70 percent of people with PNH being treated with Soliris continued to have have low hemoglobin levels, and 36 percent required one or more transfusions a year.

The new data from PEGASUS show that pegcetacoplan’s effect was seen consistently across the study population, both in patients who had low or no transfusion requirements (fewer than four transfusions in the 12 months before study entry) and high transfusion requirements (four or more transfusions). Pegcetacoplan also demonstrated a robust response across several key hematologic and clinical measures for PNH with 71 percent of pegcetacoplan-treated patients achieving LDH normalization compared to 15 percent of eculizumab-treated patients.

The results were presented in a scientific oral presentation at the 25th Congress of the European Hematology Association.

“The PEGASUS results showed that pegcetacoplan, our targeted C3 therapy, demonstrated a substantial improvement over C5 inhibition in PNH,” said Federico Grossi, chief medical officer of Apellis. “These data reinforce the potential for pegcetacoplan to elevate the standard of care in PNH, and we are in discussions with regulatory authorities to bring pegcetacoplan to the PNH community as quickly as possible.”

The data also demonstrated that pegcetacoplan reduced transfusion requirements consistently across the study population. Overall, 85 percent of pegcetacoplan-treated patients were transfusion-free over 16 weeks versus 15 percent of eculizumab-treated patients. Pegcetacoplan also showed higher normalization rates in key markers of hemolysis and clinically meaningful improvements in FACIT-fatigue score compared to eculizumab at 16 weeks.

The safety profile of pegcetacoplan was comparable to eculizumab in this study. Seven of 41 patients (17 percent) in the pegcetacoplan group experienced a serious adverse event (SAE), and 6 of 39 patients (15 percent) in the eculizumab group experienced SAEs. No cases of meningitis and no deaths were reported in either treatment group.

Apellis plans to submit a New Drug Application to the U.S. Food and Drug Administration and a Marketing Authorization Agreement to the European Medicines Agency for pegcetacoplan for the treatment of PNH in the second half of 2020.


Photo: Federico Grossi, chief medical officer of Apellis


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