Rare Daily Staff

AstraZeneca’s rare disease subsidiary Alexion said it had decided to discontinue the CHAMPION-ALS phase 3 trial of Ultomiris across in a broad population of adults with amyotrophic lateral sclerosis due to a lack of efficacy.

The decision is based on the recommendation of the Independent Data Monitoring Committee, following their review of data from a pre-specified interim analysis. No new safety findings were observed, and the data were consistent with the established safety profile of Ultomiris.

“We are disappointed by this outcome and what it means for patients with this devastating disease,” said Gianluca Pirozzi, senior vice president, head of Development and Safety, Alexion. “We continue to be confident in the potential of targeting C5 for complement-driven diseases and remain fully committed to our efforts to serve the rare disease community.” 

Amyotrophic lateral sclerosis (ALS) is a rare, fatal neurodegenerative disease that affects motor neurons (a type of nerve cell that controls voluntary movements) in the brain and spinal cord.

When the nerve cells die, the brain can no longer initiate and control muscle movement, which results in severe disability, paralysis and eventually death. People with ALS may lose the ability to speak, eat, move and breathe. The rate of progression between individuals is variable and the natural history generally reflects progressive worsening over time until death occurs. The average life expectancy from symptom onset is between two and five years. Currently approved medications may slow disease progression, but ALS management is mostly supportive, palliative and symptom based.

Patients who enrolled in the trial will discontinue study medication and complete any necessary follow-up evaluations. Data from the trial will be provided to inform ongoing research.

The CHAMPION-ALS phase 3 trial was a randomized, double-blind, placebo-controlled multicenter global trial designed to evaluate the efficacy and safety of Ultomiris across a broad ALS population. The trial enrolled 382 adults with sporadic or familial ALS who had disease onset (in the form of first motor symptoms) within the prior 36 months, demonstrated a slow vital capacity (SVC) of at least 65 percent predicted, and were not dependent on respiratory support. The primary endpoint was change in ALS functional rating scale-revised (ALSFRS-R) score. Trial participants were randomized on a 2:1 basis to receive Ultomiris or placebo every eight weeks following an initial loading dose. The trial was conducted at approximately 90 clinical trial sites across North America, Europe, and Asia.

Ultomiris is a long-acting C5 complement inhibitor that offers immediate, complete, and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. It is approved in the United States for the treatment of adults and children (one month of age and older) with paroxysmal nocturnal hemoglobinuria (PNH), as well as in the European Union and Japan as a treatment for adults with PNH. It is also approved in the United States for atypical hemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy in adult and pediatric (one month of age and older) patients, in the European Union for the treatment of adults and children with a body weight of at least 10 kg with aHUS, as well as in Japan for adults and children with aHUS.

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