Pegcetacoplan fails to improve ALS outcomes in MERIDIAN trial

Study's primary, secondary goals not met; development for ALS to cease

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by Andrea Lobo |

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Apellis Pharmaceuticals’ investigational therapy pegcetacoplan (APL-2) has failed to improve a combined assessment of function and survival in people with amyotrophic lateral sclerosis (ALS), according to top-line data from the MERIDIAN Phase 2 clinical trial.

While the treatment was well tolerated, consistent with its established safety profile, the findings mean MERIDIAN failed to meet its primary goal. Other key secondary goals, including disease progression and changes in muscle strength and lung function, also were not met.

Apellis and Sobi, which owns exclusive rights to the medication outside the U.S., plan to discontinue pegcetacoplan’s development for ALS, based on its lack of effectiveness.

The announcement follows a recent decision to discontinue pegcetacoplan treatment in MERIDIAN’s open-label portion after the trial’s independent data monitoring committee concluded the available results didn’t support its continuation.

“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,” Jeffrey Eisele, PhD, chief development officer at Apellis, said in a company press release. “We would like to sincerely thank the study participants and their caregivers from around the world who contributed to this important research.”

ALS is caused by the progressive damage and loss of motor neurons, the nerve cells that control voluntary movement. The exact mechanisms leading to the disease aren’t fully understood, but inflammation is believed to be a key driver of its progression.

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Main, secondary goals in pegcetacoplan study

Pegcetacoplan is an inhibitor of the complement protein 3 (C3), a component of the complement system. This is a part of the immune system that’s normally involved in fighting infections.

In ALS, high levels of C3 are present at the neuromuscular junctions — the sites where nerve cells communicate with muscles – contributing to inflammation and the death of motor neurons.

The MERIDIAN Phase 2  trial (NCT04579666) was designed to test pegcetacoplan in sporadic ALS patients whose symptoms had started in the past 18 months.

A total of 249 participants were enrolled at dozens of sites in the U.S., Europe, Australia, and Japan. They were randomly assigned to receive pegcetacoplan or a placebo via injections under the skin twice a week for a year. All the participants were able to continue receiving their standard of care treatment for ALS during the trial.

The trial’s main goal was to determine pegcetacoplan’s impact on a combined assessment of function and survival (CAFS), which ranks patients’ clinical outcomes based on survival time and changes in the ALS Functional Rating Scale–Revised (ALSFRS-R) score, a measure of functional decline.

Secondary goals included safety, changes in lung function and muscle strength, and functional decline. The time to death or needing respiratory support as well as the number of patients with suicidal thoughts were also assessed.

The study failed to met its primary and secondary goals, according to the company. Full MERIDIAN data is now being analyzed and is expected to be presented at a future medical meeting.

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