Apellis Pharmaceuticals announced positive topline results from the phase 3 PEGASUS trial of pegcetacoplan (APL-2) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

PNH is a very rare, life-threatening and debilitating disease characterized by complement-mediated hemolysis with or without hemoglobinuria. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that inhibits the complement cascade centrally at C3. It effectively blocks all 3 pathways of complement activation (classical, lectin, and alternative). 

In PEGASUS, the efficacy and safety of pegcetacoplan was evaluated in 80 adult patients with PNH. Patients were randomized to receive either pegcetacoplan 1080mg subcutaneously twice weekly (n=41) or eculizumab (n=39) for 16 weeks. The primary end point was the change from baseline in hemoglobin level to week 16. Key secondary end points included transfusion avoidance, absolute reticulocyte count and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score.

Findings from the study showed that pegcetacoplan met the primary end point, demonstrating superiority to eculizumab with a statistically significant improvement in adjusted means of 3.8g/dL of hemoglobin at week 16 (P <.0001). Patients in the pegcetacoplan and eculizumab treatment arms had an adjusted mean hemoglobin change of 2.4g/dL and -1.5g/dL, respectively, from a baseline of 8.7g/dL at week 16. Additionally, pegcetacoplan was found to be noninferior to eculizimab on key secondary end points. 


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The safety profile of pegcetacoplan was comparable to eculizumab with the most common adverse reactions being injection site reactions (36.6% vs 2.6%), diarrhea (22% vs 0%), headache (7.3% vs 20.5%), and fatigue (4.9% vs 15.4%), respectively.

Full detailed results will be presented at a future scientific meeting.

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“The majority of patients with PNH currently receiving treatment with eculizumab have continuing anemia,” said Peter Hillmen, MB, ChB, PhD, Professor of Experimental Hematology at the University of Leeds and an investigator in the PEGASUS study. “The PEGASUS results show that pegcetacoplan has the potential to become a new standard of care for patients with PNH.”

The Company is currently evaluating pegcetacoplan for the treatment of PNH in the following clinical trials: PRINCE (phase 3), PALOMINO (phase 2a), PADDOCK (phase 1), and PHAROAH (phase 1). Pegcetacoplan is also being investigated for the treatment of geographic atrophy, autoimmune hemolytic anemia, and glomerulopathies.

For more information visit apellis.com.