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Jun 10, 2023

Apellis stops dosing of pegcetacoplan in ALS trial after data review

No safety concerns, but results don't support continuing MERIDIAN study

No safety concerns, but results don't support continuing MERIDIAN study

by Patricia Inácio, PhD | May 10, 2023

Apellis Pharmaceuticals has discontinued treatment with pegcetacoplan (APL-2), its investigational therapy for amyotrophic lateral sclerosis (ALS), in the open-label stage of the MERIDIAN trial.

The decision follows a review of trial data by an independent data monitoring committee, which concluded that the available results did not support treatment continuation. No safety concerns were behind the committee's decision.

The company now will continue to examine the full dataset from the randomized part of MERIDIAN, which was completed by all participants. Top-line results are expected in the coming months, and the data will help inform the next steps for pegcetacoplan in ALS, Apellis said in a press release announcing its first quarter results.

Pegcetacoplan is an inhibitor of the complement protein 3, known as C3, a key component of the complement system.

This system is a part of the body's immune system, which is normally involved in fending off infections. However, an abnormal complement activation is linked with excessive inflammatory responses, which underlie multiple health conditions.

In ALS, high levels of C3 are present in the neuromuscular junctions, the sites where nerve cells and muscles communicate. This contributes to chronic inflammation and the death of motor neurons, the cells that control voluntary movement and are progressively lost in ALS.

The MERIDIAN Phase 2 trial (NCT04579666), which began dosing in late 2020, was designed to test pegcetacoplan in sporadic ALS patients whose symptoms had started less than 18 months before enrollment.

A total of 249 participants were included and randomly assigned to receive 1,080 mg of pegcetacoplan or a placebo, given via under-the-skin (subcutaneous) injections twice a week for one year. All were allowed to continue on their current ALS treatments.

The trial's main goal was to determine the impact of pegcetacoplan on a combined assessment of survival and changes in ALS Functional Rating Scores Revised (ALSFRS-R) scores, indicative of functional declines.

Secondary goals included measures of safety, and changes in physical ability, muscle strength, and lung function, as well as time to death or the need for ventilatory support. The proportion of patients with suicidal thoughts also was assessed.

Those who completed the trial's randomized part could then join an open-label extension part, in which all received pegcetacoplan for one year. However, the data gathered so far has led the trial's monitoring committee to recommend treatment discontinuation in that part.

MERIDIAN was registered as a potentially registrational trial. That means its results could potentially be used to support a request to regulatory agencies asking for the approval of pegcetacoplan for ALS.

"We want to thank all the people living with ALS and their caregivers who participated in the study and appreciate the partnerships built with the broader ALS community. We are committed to continuing our work together as we analyze the data generated from this study," Apellis stated.

"A decision on next steps for the program will be made following the planned analysis of the full data," the company added.