Pegcetacoplan to be Discontinued in ALS Following Disappointing Phase 2 Results

Author(s):

In a trial of 250 adults with sporadic ALS, pegcetacoplan failed to meet its primary end point of change in Combined Assessment of Function and Survival rank scores relative to placebo after a 52-week stretch.

Jeffrey Eisele, PhD

According to a recent announcement, the phase 2 MERIDIAN study (NCT04579666) assessing systemic pegcetacoplan (Empaveli; Apellis Pharmaceuticals), an investigational agent in development for amyotrophic lateral sclerosis (ALS), did not meet its primary and secondary end points and thus, will be discontinued.¹

Pegcetacoplan, a targeted C3 therapy designed to regulate excessive activation of the complement cascade, failed to distinguish itself from placebo on the primary end point of change in Combined Assessment of Function and Survival (CAFS) rank scores after 52 weeks of treatment. In addition, the study failed to meet other secondary end points of overall function, survival, lung function, and muscle strength.

"We are disappointed in the outcome of the MERIDIAN study, especially on behalf of the ALS community who has been waiting for new treatments for this complex and unrelenting disease. We would like to sincerely thank the study participants and their caregivers from around the world who contributed to this important research,” Jeffrey Eisele, PhD, chief development officer at Apellis, said in a statement.¹ "Our hope is that the data generated from this study will continue to support future research and development in ALS."

Apellis noted that it will continue to analyze data from the study and present findings at a future medical meeting. Although the therapy was well tolerated in the study, with no new safety findings, those in the open-label portion also discontinued their treatment following a recommendation from an independent data monitoring committee. In total, the trial featured 250 adults with sporadic ALS who had an onset of symptoms within 72 weeks, a total ALS Functional Rating Scale score of at least 30 at screening, and slow vital capacity greater than 60% of the predicted value at screening.

Pegcetacoplan was previously approved in May 2021 as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening blood disease. With the approval, the therapy became the first marketed therapy for PNH that binds to complement protein C3. The effectiveness of pegcetacoplan was evaluated in a study of 80 patients with PNH and anemia who had been taking eculizumab (Soliris; Alexion), a treatment previously approved for PNH. During the 16-week trial, patients on pegcetacoplan had an average increase in their hemoglobin of 2.4 g/dL compared with average decreases of 1.5 g/dL for those on eculizumab.²

Earlier this year, the FDA approved another indication for pegcetacoplan, marketed as Syfovre, as a treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). With that approval, it became the first and only marketed agent for GA, a leading cause of blindness that impacts more than 1 million people in the US and 5 million people worldwide. The safety profile was well demonstrated following nearly 12,000 injections, with the most common adverse events being ocular discomfort, neovascular AMD, vitreous floaters, and conjunctival hemorrhage.³

REFERENCES
1. Apellis reports top-line results from phase 2 MERIDIAN study in ALS. News release. Apellis Pharmaceuticals. May 25, 2023. Accessed June 22, 2023. https://www.globenewswire.com/news-release/2023/05/25/2675976/0/en/Apellis-Reports-Top-Line-Results-from-Phase-2-MERIDIAN-Study-in-ALS.html
2. FDA approves new treatment for adults with serious rare blood disease. News release. FDA. May 18, 2021. Accessed June 22, 2023. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-treatment-adults-serious-rare-blood-disease
3. FDA approves Syfovre (pegcetacoplan injection) as the first and only treatment for geographic atrophy (GA), a leading cause of blindness. News release. Apellis Pharmaceuticals. February 17, 2023. Accessed June 22, 2023. https://investors.apellis.com/news-releases/news-release-details/fda-approves-syfovretm-pegcetacoplan-injection-first-and-only