Alexion to Initiate Phase 3 Trial of Ultomiris for Familiar, Sporadic ALS Patients

In the coming months, Alexion Pharmaceuticals will launch a pivotal Phase 3 clinical trial to test its complement system inhibitor Ultomiris (ravulizumab) in people with amyotrophic lateral sclerosis (ALS) whose motor symptoms began in the prior three years.

The CHAMPION-ALS trial — which follows an investigational new drug application submitted to the U.S. Food and Drug Administration in late 2019 — is expected to recruit 350 patients with familial or sporadic ALS and to begin in the first quarter of 2020.

“We’ve made great progress advancing ALS research in recent years, but there is still more work to be done to ensure patients benefit from these advances in the form of new treatments,” said Calaneet Balas, CEO and president of The ALS Association, said in a press release. “It’s great that Alexion, which has an established record of bringing new treatments to patients with devastating rare diseases, is joining the fight against ALS.”

Ultomiris is a monoclonal antibody designed to bind and inhibit the activity of the C5 protein, preventing overactivation of the complement system — a set of more than 20 blood proteins forming part of the body’s innate immune defenses.

Ultomiris is approved in the U.S. for two serious blood disorders — paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome — caused by an abnormal complement system, and evidence points to a potential benefit in ALS patients, as proteins of the complement system have been implicated in disease onset and progression of motor symptoms.

“Based on preclinical data and the significant role complement activation is known to play in other neuromuscular diseases, we believe Ultomiris has the potential to inhibit complement-mediated damage in people with ALS, which may slow disease progression,” said John Orloff, MD, executive vice president and head of research and development at Alexion.

CHAMPION-ALS is a pivotal clinical trial expected to determine whether Ultomiris prevents disease progression in ALS, potentially leading to its approval for this indication.

The trial will include people whose first motor symptoms began within three years of enrollment, have a percent predicted slow vital capacity — a standard measure of respiratory function — of at least 65%, and are not dependent on respiratory support.

Participants will be recruited at approximately 90 clinical trial sites across North America, Europe, and Asia-Pacific, and be randomly assigned to Ultomiris or a placebo in a 2:1 ratio — for each patient given a placebo, two will receive Ultomiris.

Treatment will be delivered intravenously (into-the-vein) every eight weeks for a total of 50 weeks, after which all patients will receive Ultomiris in a two-year open-label extension phase. Patients will be allowed to continue to receive their standard of care treatment for ALS.

CHAMPION-ALS’s primary goal is to determine the changes in ALS Functional Rating Scale Revised within the 50-week study period. Secondary objectives include the time patients live without needing ventilation assistance, respiratory capacity, muscle strength, and levels of neurofilament light chain, which is a marker of disease severity.

“Given the significant need for new and improved treatments for ALS, we are committed to advancing this clinical program with urgency,” said Orloff. “We thank the ALS community for their involvement in designing this Phase 3 program and look forward to continue close collaboration as we move it forward.”