AstraZeneca is ending a phase 3 trial of Ultomiris, which was being evaluated as a treatment for amyotrophic lateral sclerosis (ALS). The pharmaceutical company acquired the C5 inhibitor after buying Alexion’s rare disease franchise. This early finish was recommended by an independent committee, which pointed out that Ultomiris was not meeting efficacy endpoints.
Ultomiris for ALS
This C5 inhibitor was investigated in the phase 3 Champion-ALS trial, with a planned top-line readout for the first half of 2022. Unfortunately, the trial ended much earlier than expected when a review by an independent committee revealed issues with efficacy.
Originally, Alexion believed that Ultomiris would be able to reduce the neuroinflammation that characterizes ALS, as it focuses on the complement system. Theoretically, this would allow ALS patients to live longer. However, when put to the test in a proof-of-concept study, the drug failed to prove its efficacy.
Ultomiris and Other Indications
While Ultomiris has failed to prove itself as a treatment for ALS, it has already received approval for other indications. At the time of this article, the drug has been approved for the treatment of atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH).
Additionally, it’s still being evaluated for other rare conditions, such as myasthenia gravis (MG) and neuromyelitis optica spectrum disorder (NMOSD). In fact, a phase 3 trial investigating Ultomiris for MG has already met its endpoint in comparison to placebo, and results from the NMOSD study are expected by the end of next year.
About ALS
Amyotrophic lateral sclerosis (ALS) is a progressive, neurological disease in which nerve cells in the brain stem, brain, and spinal cord deteriorate. Due to this deterioration, muscles weaken, and people lose control of them along with their voluntary movement. In the late stages of ALS, the muscles necessary for breathing weaken, resulting in death.
There are two forms of this disease: sporadic and familial. The former is the most common, with 90-95% of cases falling into this category. In the familial form of the disease, it is known that a mutated gene is inherited from parents, but it is still not fully understood and only accounts for 5-10% of cases. Otherwise, the cause of ALS is unknown. Researchers believe that there is a connection between frontotemporal dementia and ALS. Another theory is that exposure to certain substances or toxins leads to the development of ALS.
Symptoms of ALS vary between individuals. They also worsen as the disease progresses. Symptoms begin with difficulty with small movements and everyday things like walking. At the onset of the disease, people may trip and feel weakness in their arms, hands, and legs. As it progresses, people experience difficulties with speaking and swallowing, slowed and slurred speech, twitches and cramps in the muscles, and difficulty holding good posture. In the later stages, people will be unable to move their muscles gradually. This inability affects movements like blinking. While people with ALS experience loss of muscle function, they do not lose any of their cognitive abilities.
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