Empaveli Approved for Paroxysmal Nocturnal Hemoglobinuria

Empaveli is a complement inhibitor that binds to complement protein C3 and its activation fragment C3b.

The Food and Drug Administration (FDA) has approved Empaveli™ (pegcetacoplan) for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

Empaveli is a complement inhibitor that binds to complement protein C3 and its activation fragment C3b, thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation. The approval was based on data from the 16-week, randomized, open-label, active comparator-controlled phase 3 PEGASUS study (ClinicalTrials.gov: NCT03500549) that compared the efficacy and safety of Empaveli to eculizumab in 80 adults with PNH. 

Findings from the study showed that Empaveli met the primary endpoint, demonstrating superiority to eculizumab with an adjusted mean increase from baseline in hemoglobin level of 3.84g/dL (95% CI, 2.33-5.34; P <.0001) at week 16. Moreover, Empaveli was found to be noninferior to eculizumab on key secondary endpoints including transfusion avoidance and absolute reticulocyte count.

As for safety, the most common adverse reactions reported with Empaveli (≥10%) included injection site reactions (39%), infections (29%), diarrhea (22%), abdominal pain (20%), respiratory tract infection (15%), viral infection (12%), and fatigue (12%). Use of Empaveli may predispose patients to serious infections, especially those caused by encapsulated bacteria such as Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B (Hib). As such, the product is only available through a restricted program called the Empaveli REMS.

“As the first, FDA-approved targeted C3 therapy, Empaveli has the potential to redefine treatment for adults with PNH, including patients switching from any C5 inhibitor and treatment-naïve patients,” said Cedric Francois, MD, PhD, co-founder and chief executive officer, Apellis. “This approval represents a major scientific advancement as Empaveli ushers in the first new class of complement medicine in almost 15 years.”

Empaveli is supplied as 1080mg/20mL solution in a single-dose vial for subcutaneous infusion. The Company is providing a patient assistance program called ApellisAssist™ to support patients receiving Empaveli.


  1. FDA approves new treatment for adults with serious rare blood disease. [press release]. Silver Springs, MD: US Food and Drug Administration; May 14, 2021. 
  2. Apellis announces U.S. Food and Drug Administration (FDA) approval of Empaveli™ (pegcetacoplan) for adults with paroxysmal nocturnal hemoglobinuria (PNH). [press release]. Waltham, MA: Apellis Pharmaceuticals, Inc.; May 14, 2021.
  3. Empaveli [package insert]. Waltham, MA: Apellis Pharmaceuticals, Inc.; 2021.