FDA Approval and Drug Profile

The U.S. FDA approved Apellis Pharmaceuticals (APLS)' Empaveli (pegcetacoplan) on May 14, 2021, for the treatment of adult paroxysmal nocturnal hemoglobinuria (PNH). Empaveli is the first C3 inhibitor for PNH, binding to complement proteins C3 and C3b to inhibit both intravascular and extravascular hemolysis. It is administered subcutaneously at 1,080mg twice weekly. The FDA applied Priority Review, Fast Track, and Orphan Drug designation, and did not refer the drug to an advisory committee (AdComm) as it deemed no external advisory input necessary for efficacy and safety concerns. Approval was granted under full marketing authorization, and a Risk Evaluation and Mitigation Strategy (REMS) including vaccination and restricted distribution is in place due to the risk of serious encapsulated bacterial infections.

Differentiation Proven by PEGASUS Trial

Approval was based on the Phase 3 PEGASUS trial, a randomized open-label study involving 80 adults with persistent anemia despite eculizumab therapy. At 16 weeks, the average hemoglobin level increased by 2.4g/dL in the Empaveli group, while it decreased by 1.5g/dL in the Soliris (eculizumab) group, demonstrating the clinical superiority of C3 inhibition over C5. The transfusion avoidance rate was 85% for Empaveli and 15% for Soliris, providing evidence not only of symptom improvement but also of reduced transfusion resources and patient burden. However, since C3 inhibition broadly affects the infection defense system, management of pneumococcal, meningococcal, and Haemophilus influenzae B vaccines is a critical condition for commercial adoption.

Competitive Landscape and Market Potential

The current standard of care includes Alexion, a subsidiary of AstraZeneca (AZN), C5 inhibitors Soliris and Ultomiris (ravulizumab-cwvz), approved on December 21, 2018. Novartis (NVS)' oral Factor B inhibitor Fabhalta (iptacopan) was approved on December 5, 2023, and Alexion's oral Factor D inhibitor Voydeya (danicopan) was approved on March 29, 2024, for adjunctive therapy in patients with extravascular hemolysis during C5 treatment. The global PNH treatment market is estimated at approximately USD 4.5 billion in 2024, with high-cost chronic complement inhibition therapies forming a significant market despite the disease's rarity. Empaveli's U.S. net product sales reached USD 102.4 million in 2025, up from USD 98.1 million in 2024, but the convenience of oral monotherapy Fabhalta is a direct competitive constraint on market share expansion.

Global Rights and Transaction Structure

Apellis retains U.S. rights, while Swedish Orphan Biovitrum (STO:SOBI) holds exclusive commercialization and co-development rights for the full-acting pegcetacoplan outside the U.S. In Europe, it was approved by the EMA under the brand name Aspaveli on December 13, 2021, and in Japan, Empaveli received PMDA approval in March 2023. The 2020 agreement included an upfront payment of USD 250 million, development cost reimbursement up to USD 80 million, regulatory and commercial milestones up to USD 915 million, and tiered royalties in the high-teens to high-twenties range on non-U.S. sales. This structure allows Apellis to maintain U.S. sales economics while leveraging Sobi's rare disease distribution network to share international market entry costs and execution risks.