Apellis ALS Candidate Fails in Phase 2 Study

Rare Daily Staff

Apellis Pharmaceuticals reported that the phase 2 MERIDIAN study investigating systemic pegcetacoplan for the treatment of amyotrophic lateral sclerosis did not meet its primary endpoint and key secondary efficacy endpoints.

The study found systemic pegcetacoplan was well tolerated and the data were consistent with the established safety profile.

ALS is a devastating neurodegenerative disease that results in progressive muscle weakness and paralysis due to the death of nerve cells, called motor neurons, in the brain and spinal cord. The death of motor neurons leads to the progressive loss of voluntary muscle movement required for speaking, walking, swallowing, and breathing. There are currently no approved treatments that stop or reverse the progression of ALS, which impacts approximately 225,000 patients worldwide.

Pegcetacoplan is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, a part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is under investigation for several rare diseases across hematology, nephrology, and neurology. Pegcetacoplan is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) as EMPAVELI in the United States, Australia, Canada, and Saudi Arabia and in the European Union and the United Kingdom as Aspaveli.

Based on the lack of efficacy, Apellis and Sobi plan to discontinue development of systemic pegcetacoplan for amyotrophic lateral sclerosis (ALS). In April, Apellis and Sobi discontinued treatment in the open-label portion of the study, following a recommendation from an independent data monitoring committee.

“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,” said Jeffrey Eisele, chief development officer of Apellis. “Our hope is that the data generated from this study will continue to support future research and development in ALS.”

The phase 2 MERIDIAN study is a randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of systemic pegcetacoplan in approximately 250 adults with sporadic amyotrophic lateral sclerosis (ALS). Study participants were randomized in a 2:1 ratio to receive pegcetacoplan or placebo while continuing to receive their existing standard of care treatment for ALS for 52 weeks. The primary endpoint of the study is the Combined Assessment of Function and Survival (CAFS) rank scores. Key secondary endpoints include measures of overall function, survival, lung function, and muscle strength. After 52 weeks, all study participants were to receive pegcetacoplan. To reduce the burden on people living with ALS and their caregivers, the study has been designed to minimize the number of in-clinic visits.

The full MERIDIAN dataset is being analyzed, and detailed data is expected to be presented at a future medical meeting.

Apellis and Sobi have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy.

Photo: Jeffrey Eisele, chief development officer of Apellis