Ultomiris (ravulizumab-cwvz) is an antibody-based medication that was being developed by Alexion Pharmaceuticals as a potential therapy for amyotrophic lateral sclerosis (ALS). However, after a Phase 3 clinical trial indicated that Ultomiris was not effective in treating ALS, Alexion in 2021 discontinued its development for the neurological disorder.
While top-line results of the ALS trial were not originally expected until mid-2022, an independent data monitoring committee recommended the study be stopped early due to the lack of Ultomiris’ efficacy in a pre-specified interim analysis.
In the U.S., the therapy is approved to treat atypical hemolytic uremic syndrome, known as aHUS, and paroxysmal nocturnal hemoglobinuria, two diseases in which the immune system erroneously attacks red blood cells. With both these disorders, the treatment works by blocking the activity of the complement cascade, a part of the immune system.
How does Ultomiris work?
The complement cascade refers to a group of immune proteins in the blood. Normally, these proteins float around in the blood in an inactive state, but in response to certain inflammatory stimuli — for example, an infectious bacteria — the proteins become activated, triggering an inflammation and clotting response that can help to repel the infectious invader.
However, abnormal activity of complement has been implicated in the development and progression of ALS and other neuromuscular diseases.
Ultomiris contains an antibody that is injected into the bloodstream and that stops a complement protein called C5, thereby blocking the activation of the complement cascade.
Ultomiris in clinical trials
Alexion launched the Phase 3 clinical trial, called CHAMPION-ALS (NCT04248465), in early 2020. The trial, conducted at 95 sites around the globe, enrolled 382 people with ALS who were not dependent on ventilatory support and had been diagnosed in the previous three years.
Participants were randomly assigned to receive Ultomiris or a placebo once every eight weeks, or about every two months, given along with their standard of care treatments.
The CHAMPION-ALS trial had originally been planned to run for a total of 50 weeks, or just short of one year, followed by an extension study. Its main goal was to test whether the treatment slowed the rate of disease progression, as assessed by changes in ALS Functional Rating Scale-Revised.
However, the trial’s data monitoring committee — an outside group of experts tasked with ensuring the integrity of trial data and safety of participants — recommended that the trial be stopped early in August 2021, after an analysis of interim data from the trial indicated that the treatment was not effective at slowing disease progression. No new findings related to the safety of Ultomiris were noted.
Last updated: Oct. 4, 2021
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