Another ALS Hopeful Falls Short as Alexion Halts Phase III Trial

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Alexion, the unit within global pharmaceutical firm AstraZeneca that focuses on finding treatments for rare diseases, has announced that it is halting clinical trials for a drug they previously thought would address ALS.

In a statement, the group said that the Phase III trial of Ultomiris (ravulizumab) lacked efficacy when it was used on adults diagnosed with amyotrophic lateral sclerosis (ALS). The Independent Data Monitoring Committee (IDMC) recommended its stoppage after looking at interim analyses. There were no new safety findings observed during the study and all the data had remained consistent throughout. 

The CHAMPION-ALS Phase III trial was a randomized, double-blind, placebo-controlled global trial to assess the safety and efficacy on Ultomiris across a broad spectrum of ALS cases. The study involved 382 participants with either sporadic or familial ALS whose disease onsets were within the 36 months before the trial commenced. The recipients reportedly had a slow vital capacity of at least 65 percent and did not need respiratory support. 

The participants received Ultomiris or placebo on a 2:1 basis every eight weeks from the initial dose and were conducted in 90 sites across Asia, Europe, and North America. The primary endpoint was a change in ALS functional rating scale-revised (ALSFRS-R) score. 

Ultomiris is the first and only long-acting C5 complement inhibitor that 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, it could lead the body to attack its own healthy cells. The drug is approved in the U.S., the EU, and Japan to treat adults and children ages one month and older who are diagnosed with paroxysmal nocturnal haemoglobinuria (PNH). It was also approved in the U.S. for atypical hemolytic uraemic syndrome (aHUS) for various candidate profiles. 

As a result of the decision to stop the CHAMPION-ALS trial, enrolled patients will immediately discontinue the medication and complete any necessary follow-ups. Data will be kept as a reference for ongoing research. 

"We are disappointed by this outcome and what it means for patients with this devastating disease. We would like to thank the entire ALS community as well as investigators and healthcare professionals who dedicated their time and expertise to this trial," said Gianluca Pirozzi, MD, Ph.D., Senior Vice President and Head of Development and Safety at 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."

ALS is a neurological disease that shows a progressive degeneration of motor neurons in the brain and spinal cord, leading to severe disability, paralysis, and death. Patients diagnosed with ALS might lose the ability to eat, speak, move, and breathe. The average life expectancy from the onset of symptoms is two to five years. To date, currently approved medications can only slow the progression of the disease, with only supportive and palliative interventions. It has no cure.

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