Plain language summary: treatment of paroxysmal nocturnal hemoglobinuria with pegcetacoplan for 48 weeks (PEGASUS study)

Abstract

What is this summary about?

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, serious blood disease, characterized by uncontrolled activation of the complement system that causes hemolysis (destruction of red blood cells). The complement component 5 (C5) inhibitor eculizumab was the first approved treatment for PNH. The PEGASUS trial compared eculizumab with pegcetacoplan, a new complement component 3 (C3) inhibitor. Because C3 is activated before C5, blocking C3 would also block C5; thus, a C3 inhibitor might prevent hemolysis more completely than a C5 inhibitor in patients with PNH. During the first 16 weeks of PEGASUS, patients received either pegcetacoplan or eculizumab; results were published separately. This summary describes results of the following 32 weeks of PEGASUS, during which all patients received pegcetacoplan to evaluate if pegcetacoplan continued to be effective and safe for up to 48 weeks.

What were the results?

Pegcetacoplan continued to be effective in participants who received it throughout the study and improved symptoms in participants who switched from eculizumab. The most common adverse events (side effects) were skin irritation at the injection site, hemolysis, nasopharyngitis (runny nose and sore throat), and diarrhea. Adverse events were serious and related to pegcetacoplan in 4 of 77 (5%) patients; all patients recovered from these events.

What do the results mean?

Pegcetacoplan improved symptoms and was well tolerated for up to 48 weeks by most patients in PEGASUS, suggesting that adult patients with PNH may benefit from long-term pegcetacoplan treatment.

Tweetable abstract

The PEGASUS study found that after 16 weeks, pegcetacoplan increased hemoglobin better than eculizumab did in adults with PNH. During the PEGASUS open-label period, pegcetacoplan continued to be effective and was well tolerated by most patients for up to 48 weeks.

Keywords: :

• anemia
• complement
• hemolysis
• paroxysmal nocturnal hemoglobinuria (PNH)
• pegcetacoplan

Acknowledgments

Thank you to the participants, their caregivers, the institution staff, and the study investigators for their participation in and valuable contributions to the PEGASUS study. Participants in clinical studies belong to a community of people who take part in clinical research around the world. They help researchers answer important health questions and find medical treatments for patients. The authors also thank Temitayo Ajayi for her work as an author on the original study.

Financial disclosure

This plain language summary was prepared by Apellis Pharmaceuticals, Inc., and Swedish Orphan Biovitrum AB. RPdL is a consultant for Novartis, Pfizer, Amgen, Alexion, Apellis, and Swedish Orphan Biovitrum; has received honoraria from Novartis, Pfizer, Amgen, Alexion, Apellis, and Swedish Orphan Biovitrum; has received research funding from Novartis, Pfizer, Amgen, and Alexion; and has received grants from Alexion, Amgen, Novartis, and Pfizer. JS is a consultant for Novartis, Alexion, and Apellis; has received honoraria from Takeda, Pfizer, Novartis, Prevail Therapeutics, and Alexion; is a member of the speakers bureau at Takeda, Pfizer, Novartis, and Alexion; and reports membership on an entity's board of directors or advisory committees at Prevail Therapeutics and Alexion. IW is a consultant for Alexion, Apellis, BioCryst, Novartis, and Sanofi Genzyme; has received honoraria from Alexion, Apellis, BioCryst, Novartis, and Sanofi Genzyme; and is a member of the speakers bureau at Alexion. AR reports receiving personal fees from Alexion, Apellis, Kira, Novartis, Roche, Swedish Orphan Biovitrum, Sanofi, Bioverativ, and Grifols; and has received grants from Roche. BH has received honoraria from and is an advisory board member at Novartis, Roche, Alexion, Apellis, and Swedish Orphan Biovitrum. JP is a consultant for and has received honoraria from Blueprint Medicines, Amgen, F. Hoffmann-La Roche, MSD, Bristol Myers Squibb, Alexion, Novartis, Pfizer, Gilead, Boehringer Ingelheim, Swedish Orphan Biovitrum, and Apellis; and has received honoraria from Swixx BioPharma. KU has received grants from Alexion, Apellis, Chugai, and Novartis; and reports receiving personal fees from Novartis, Chugai, and Alexion. MG is a consultant for BioCryst and Regeneron; has received honoraria from Alexion and Swedish Orphan Biovitrum; is an advisory board member at Novartis, BioCryst, Alexion, Amgen, and Swedish Orphan Biovitrum; and reports educational work sponsored by Apellis with an unrestricted grant paid to Medscape. J-JK reports membership on an entity's board of directors or advisory committees at AbbVie, Novartis, Bristol Myers Squibb, and AOP Health (previously AOP Orphan). CdC is a consultant for Apellis; has received honoraria from Novartis, Alexion, BioCryst, and Apellis; and has received research funding from Alexion and Apellis. HN declares no competing interests. MA-A was an employee of Apellis at the time of the study. PD reports being a founder, chief scientific officer, and current equity holder at Apellis. CF reports current employment and current equity holder at Apellis. AR is a consultant for Novartis and Amyndas; reports membership on an entity's board of directors or advisory committees at Novartis, Alexion, Samsung, BioCryst, Achillion, Roche, Sanofi, and Apellis; and has received grants from Alexion, Novartis, Alnylam, and Rapharma. PH is a consultant for Alexion, Apellis, AbbVie, AstraZeneca, Janssen, and Roche; has received research funding from Alexion, Apellis, AbbVie, Gilead, Janssen, Pharmacyclics, and Roche; and is a member of the speakers bureau at Alexion, Apellis, AbbVie, AstraZeneca, Janssen, and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

Additional writing and editing assistance, including preparation of a draft plain language summary under the direction and guidance of the authors, incorporation of author feedback, and submission, was provided by Catherine Champagne, PhD (Kay Square Scientific, Newtown Square, PA, USA). This support was funded by Apellis Pharmaceuticals and Swedish Orphan Biovitrum.

Data sharing statement

The study is complete. However, some patients are participating in an ongoing, long-term, open-label, extension study to evaluate the efficacy and safety of pegcetacoplan for up to 4 years. Access to patient-level data with qualified external researchers may be available upon request once the extension study is complete and data are published.