New Pivotal Data Demonstrate Superiority of Apellis’ Pegcetacoplan to Eculizumab in Improving Hemoglobin Levels, Independent of Prior Transfusions, in PNH

Waltham, Massachusetts, UNITED STATES

  • 71% of pegcetacoplan-treated patients achieved LDH normalization vs. 15% of eculizumab-treated patients

  • 73% of pegcetacoplan-treated patients achieved a clinically meaningful improvement in FACIT-fatigue score vs. 0% of eculizumab-treated patients
  • Detailed results from positive head-to-head Phase 3 PEGASUS study in patients with paroxysmal nocturnal hemoglobinuria (PNH) presented in oral session at 25th Congress of the European Hematology Association
  • NDA and MAA submissions planned in H2 2020. Conference call scheduled today at 8:30 a.m. ET

WALTHAM, Mass., June 12, 2020 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company pioneering targeted C3 therapies, today presented detailed results from the Phase 3 PEGASUS study, which in January showed superiority (p<0.0001) for pegcetacoplan over eculizumab in improving hemoglobin levels in adults with paroxysmal nocturnal hemoglobinuria (PNH). New data from the pivotal study showed 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. The results were presented in a scientific oral presentation at the 25th Congress of the European Hematology Association (EHA).

Pegcetacoplan met the study’s primary endpoint for efficacy, demonstrating superiority to eculizumab with a statistically significant improvement in adjusted means of 3.8 g/dL of hemoglobin at week 16 (p<0.0001), 53% higher than the eculizumab arm.

  • In patients with low or no transfusion requirements, pegcetacoplan-treated patients (n=20) had an adjusted mean hemoglobin increase of 2.97 g/dL vs. eculizumab-treated patients (n=16) who had a mean change of -0.01 g/dL from the 8.9 g/dL baseline.
  • In patients with high transfusion requirements, pegcetacoplan-treated patients (n=21) had an adjusted mean hemoglobin increase of 2.11 g/dL vs. eculizumab-treated patients (n=23) who had a mean change of -4.02 g/dL from the 8.5 g/dL baseline.1

“The PEGASUS results showed that pegcetacoplan, our targeted C3 therapy, demonstrated a substantial improvement over C5 inhibition in PNH,” said Federico Grossi, M.D., Ph.D., 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.”

Data presented at EHA demonstrated that pegcetacoplan reduced transfusion requirements consistently across the study population. Overall, 85% of pegcetacoplan-treated patients were transfusion-free over 16 weeks vs. 15% of eculizumab-treated patients. In patients with low or no transfusion requirements, 85% of pegcetacoplan-treated patients were transfusion-free compared to 31% of eculizumab-treated patients. In patients with high transfusion requirements, 86% of pegcetacoplan-treated patients were transfusion-free compared to 4% 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:

  • 78% of pegcetacoplan-treated patients achieved reticulocyte normalization vs. 3% of eculizumab-treated patients.
  • 71% of pegcetacoplan-treated patients achieved LDH normalization vs. 15% of eculizumab-treated patients.
  • 73% of pegcetacoplan-treated patients achieved at least a three-point improvement in FACIT-fatigue score vs. 0% of eculizumab-treated patients. A three-point improvement in FACIT-fatigue score is generally considered to be clinically meaningful.2

“Even with current treatments, the anemia and relentless fatigue caused by C3-driven extravascular hemolysis continue to be a significant problem for people living with PNH,” said Peter Hillmen, M.B., Ch.B., Ph.D., Professor of Experimental Hematology at the University of Leeds and an investigator in the PEGASUS study. “These results demonstrate that pegcetacoplan controls both extravascular and intravascular hemolysis, and has the potential to become a new standard of care for PNH.”

As previously reported, the safety profile of pegcetacoplan was comparable to eculizumab in this study. Seven of 41 patients (17%) in the pegcetacoplan group experienced a serious adverse event (SAE), and 6 of 39 patients (15%) 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 (NDA) to the U.S. Food and Drug Administration and a Marketing Authorization Agreement (MAA) to the European Medicines Agency for pegcetacoplan for the treatment of PNH in the second half of 2020.

Conference Call and Webcast
Apellis will host a conference call and webcast with Dr. Peter Hillmen to discuss the results of the PEGASUS Phase 3 clinical study on June 12 at 8:30 a.m. ET. To access the conference call, please dial (866) 774-0323 (local) or (602) 563-8683 (international) at least 10 minutes prior to the start time and refer to conference ID 7291583. A live audio webcast of the event and accompanying slides may also be accessed through the “Events and Presentations” page of the “Investors and Media” section of the company’s website at A replay of the webcast will be available for 30 days following the event.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH is a rare, chronic, life-threatening blood disorder characterized by the destruction of oxygen-carrying red blood cells through extravascular and intravascular hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue and difficulty breathing (dyspnea). Retrospective studies show that, even on eculizumab, approximately 70% of people with PNH have low hemoglobin levels,3,4 and 36% require one or more transfusions a year.3

About the PEGASUS Study
The PEGASUS study (APL2-302; NCT03500549) 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. Participants must have been on eculizumab (stable for at least 3 months) with a hemoglobin level of <10.5 g/dL at the screening visit. During the four-week run-in, patients were dosed with 1080 mg of pegcetacoplan twice weekly (n=41) in addition to their current dose of eculizumab. During the 16-week randomized, controlled period, patients were randomized to receive either 1080 mg of pegcetacoplan twice weekly or their current dose of eculizumab (n=39). All participants completing the randomized controlled period entered the open-label pegcetacoplan treatment period. Normalization rates for hematological parameters in the study were based on the upper and lower limits provided by the study’s central lab.

About Pegcetacoplan (APL-2)
Pegcetacoplan is an investigational, 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 paroxysmal nocturnal hemoglobinuria (PNH), geographic atrophy (GA), cold agglutinin disease, and C3 glomerulopathy. Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of PNH and the treatment of GA. For additional information regarding our clinical trials, visit

About Apellis
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. By pioneering targeted C3 therapies, we aim to develop best-in-class and first-in-class therapies for a broad range of debilitating diseases that are driven by uncontrolled or excessive activation of the complement cascade, including those within hematology, ophthalmology, and nephrology. For more information, please visit

Apellis Forward-Looking Statement
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the implications of preliminary clinical data. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether the company’s clinical trials will be fully enrolled and completed when anticipated; whether preliminary or interim results from a clinical trial will be predictive of the final results of the trial; whether results obtained in preclinical studies and clinical trials will be indicative of results that will be generated in future clinical trials; whether pegcetacoplan will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of the company’s clinical trials will warrant regulatory submissions and whether pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for GA, PNH, CAD, C3G or any other indication when expected or at all; whether, if Apellis’ products receive approval, they will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on April 29, 2020 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Media Contact:
Mark Dole

Investor Contact: 
Sam Martin / Maghan Meyers
Argot Partners /

1 Based on the pre-specified analysis, hemoglobin levels following transfusions were excluded. This was done to isolate the impact of the treatment from that of transfusions, which can otherwise artificially increase hemoglobin levels. This explains why a drop in hemoglobin levels can be observed in patients with high transfusion requirements in the eculizumab group.

2 Cella D, et al. J Pain Symptom Manage. 2002;24(6):547-561. 2. Nordin A, et al. BMC Med Res Methodol. 2016;16:62.

3 Risitano AM, Marotta S, Ricci P, et al. (2019) Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT. Front. Immunol. 10:1157. doi: 10.3389/fimmu.2019.01157.

4 McKinley C. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130:3471.