Apellis Announces FDA Acceptance & Priority Review of NDA

Apellis Pharmaceuticals, Inc. recently announced the US FDA has accepted and granted Priority Review designation for the New Drug Application (NDA) for pegcetacoplan for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). The Prescription Drug User Fee Act (PDUFA) target action date is May 14, 2021. The FDA has stated that it is not currently planning to hold an advisory committee meeting to discuss the application.

“For more than a decade, the only treatment options available for PNH have been C5 inhibitors, and many patients still suffer from persistently low hemoglobin, often resulting in debilitating fatigue and frequent transfusions. The NDA priority review takes us one step closer to bringing pegcetacoplan, a targeted C3 therapy with the potential to redefine PNH treatment, to patients in need,” said Federico Grossi, MD, PhD, Chief Medical Officer of Apellis. “The data in the application validate the broad potential of targeting C3, and we continue to advance several registrational studies in serious diseases with few or no treatments.”

The NDA submission is based on results from the head-to-head Phase 3 PEGASUS study, which met its primary endpoint, demonstrating the superiority of pegcetacoplan to eculizumab with a statistically significant improvement in hemoglobin levels at 16 weeks. The data also demonstrated higher normalization rates across key markers of hemolysis and a clinically meaningful improvement in Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score. The safety profile of pegcetacoplan was comparable to eculizumab in the study.

Priority Review designation is granted to marketing applications for medicines that treat a serious condition and if approved, would provide a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition. Pegcetacoplan was previously granted Fast Track designation by the FDA for the treatment of PNH.

Apellis plans to open an early access program (EAP) in the US for pegcetacoplan for patients with PNH who are experiencing ongoing disease activity despite treatment with C5 inhibition. The EAP will be available for a limited time while the FDA is reviewing the pegcetacoplan NDA. EAPs are potential pathways for patients with life-threatening or serious diseases to access investigational therapies outside of clinical trials when no comparable or satisfactory alternative therapy options are available. More information on the EAP is available at https://apellis.com/for-patients/early-access-program/.

The PEGASUS study (APL2-302; NCT03500549) is a multi-center, randomized, active-comparator controlled Phase 3 study in 80 adults with paroxysmal nocturnal hemoglobinuria (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 three 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.

The study was conducted in collaboration with SFJ Pharmaceuticals, who supported the development of pegcetacoplan in PNH. SFJ is a global drug development company, which provides a unique and highly customized co-development partnering model for the world’s top pharmaceutical and biotechnology companies.

Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, 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 across hematology, ophthalmology, nephrology, and neurology. Pegcetacoplan was granted Fast Track designation by the FDA for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and the treatment of geographic atrophy, and received orphan drug designation for the treatment of C3G by the FDA and European Medicines Agency. For additional information regarding our clinical trials, visit https://apellis.com/our-science/clinical-trials.

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, hemoglobinuria, and difficulty breathing (dyspnea). A retrospective analysis shows that, even on eculizumab, approximately 72% of people with PNH have anemia, a key indicator of ongoing hemolysis. The analysis also finds that 36% of patients require one or more transfusions a year and 16% require three or more.

Apellis and Sobi entered a collaboration to develop and commercialize systemic pegcetacoplan in October 2020. The companies have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-US commercialization rights for systemic pegcetacoplan, and Apellis has exclusive US commercialization rights for systemic pegcetacoplan and retains worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy (GA).

Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop transformative therapies for a broad range of debilitating diseases that are driven by excessive activation of the complement cascade, including those within hematology, ophthalmology, and nephrology. For more information, please visit http://apellis.com.