Dosing Begins in Phase 2 Study of Pegcetacoplan in ALS Patients

A first patient has been dosed in the Phase 2 trial investigating pegcetacoplan (APL-2), Apellis Pharmaceuticals‘ candidate therapy for amyotrophic lateral sclerosis (ALS), the company and the Swedish Orphan Biovitrum (Sobi) announced.

The potentially pivotal trial, called MERIDIAN (NCT04579666), is currently enrolling patients at the Austin Neuromuscular Center. It aims to recruit 228 adults with sporadic ALS and symptom onset within the last 18 months at the Texas site, with other centers expected to be added.

“We are delighted that the first patient in the Phase 2 clinical study has been dosed as there is an urgency for a treatment for patients with ALS,” Ravi Rao, head of R&D and chief medical officer at Sobi, said in a press release. “In collaboration with Apellis, we look forward to evaluating the potential of pegcetacoplan in patients with ALS.”

The complement system, a group of proteins in the blood that form part of the immune system, is believed to participate in the onset and progression of multiple diseases.

In ALS patients, excessive levels of a key component of that system, called the complement protein 3 (C3), is found at neuromuscular junctions — the place where neurons and muscle fibers communicate to control movement. Those high levels are believed to trigger the inflammatory responses that contribute to the death of motor neurons.

Pegcetacoplan is an inhibitor of the C3 protein, designed to lower inflammation at neuromuscular junctions and so preserve motor neurons, which are lost over the course of ALS.

“Based on the suspected role of C3 in ALS, we are working urgently to understand whether pegcetacoplan, a targeted C3 therapy, has the potential to slow disease progression and make a difference for the ALS community,” said Federico Grossi, MD, PhD, chief medical officer of Apellis.

“We designed the MERIDIAN study based on significant feedback from the community, and we are dedicated to continuing our partnership to one day bring a meaningful therapy to families living with ALS,” Grossi added.

In the trial, patients are being randomly assigned to either pegcetacoplan or a placebo, both administered as under-the-skin (subcutaneous) injections twice weekly for one year. All enrolled may continue taking their current standard of care ALS treatments.

Patients who complete the trial’s first year can then join its open-label second year, where all will receive pegcetacoplan.

MERIDIAN’s primary goal is to determine whether pegcetacoplan outperforms placebo at preserving physical function and extending survival — assessed via a combined score of physical function and survival — over one year of treatment.

Secondary measures, some of whose assessments reach out two years, include safety and the proportion of patients with suicidal thoughts, as well as changes in lung function, muscle strength, and quality of life.

MERIDIAN is a potentially registrational, or pivotal trial, meaning its results may be used to support a regulatory request for pegcetacoplan’s approval as a disease treatment.

“ALS patients have a very high unmet need. They expect more and better treatment options,” said Bashar Al-Nakhala, chief operations officer of the ALS Therapeutic Development Institute. “We are pleased that Apellis and Sobi have joined the ALS clinical development community with our shared goal of halting the devastating progression of ALS.”