Pegcetacoplan: First Approval

• Published in: Drugs (New York, N.Y.) N.Y.), 2021-08, Vol.81 (12), p.1423-1430
• Main Author: Hoy, Sheridan M.
• Format: Article
• Language: English
• Subjects: AdisInsight Report; Adults; Agreements; Amyotrophic lateral sclerosis; Anemia; Anemia, Hemolytic, Autoimmune - drug therapy; Autoimmune hemolytic anemia; Collaboration; Complement; Complement activation; Complement C3 - antagonists & inhibitors; Complement C3b - antagonists & inhibitors; Complement component C3; Complement component C3b; Complement Inactivating Agents - pharmacology; Complement Inactivating Agents - therapeutic use; Complement system; Drug dosages; Eye diseases; Geographic Atrophy - drug therapy; Glomerulonephritis - drug therapy; Hemoglobin; Hemoglobinuria, Paroxysmal - drug therapy; Hemolysis; Humans; Infusion pumps; Internal Medicine; Macular degeneration; Medicine; Medicine & Public Health; Patients; Peptides; Peptides, Cyclic - pharmacology; Peptides, Cyclic - therapeutic use; Pharmaceuticals; Pharmacology/Toxicology; Pharmacotherapy; Streptococcus infections
• ISSN: 0012-6667; 1179-1950
• DOI: 10.1007/s40265-021-01560-8

Pegcetacoplan (Empaveli™) is a PEGylated pentadecapeptide developed by Apellis Pharmaceuticals for the treatment of complement-mediated diseases. It binds to complement component 3 (C3) and its activation fragment C3b, controlling the cleavage of C3 and the generation of the downstream effectors of complement activation and thus both C3b-mediated extravascular haemolysis and terminal complement-mediated intravascular haemolysis. Pegcetacoplan is the first C3-targeted paroxysmal nocturnal haemoglobinuria (PNH) therapy to be approved (in May 2021) in the USA, where it is indicated for the treatment of adults with PNH, including those switching from C5 inhibitor therapy with eculizumab and ravulizumab. A regulatory assessment of pegcetacoplan for the treatment of PNH is currently underway in the EU and Australia. Pegcetacoplan is also being investigated as a therapeutic option in other complement-mediated diseases, including age-related macular degeneration, C3 glomerulopathy and autoimmune haemolytic anaemia. The recommended dosage regimen of pegcetacoplan is 1080 mg twice weekly, administered as a subcutaneous infusion via an infusion pump with a ≥ 20 mL reservoir. This article summarizes the milestones in the development of pegcetacoplan leading to this first approval for the treatment of adults with PNH.