Promising results from a Phase 2 clinical trial show AMX0035 (Amylyx Pharmaceuticals), a combination of sodium phenylbutyrate and tauroursodeoxycholic acid, may slow disease progression in individuals with amyotrophic lateral sclerosis (ALS). The news comes days after the passing of Pete Frates who championed the ‘Ice Bucket Challenge’, raising global awareness of the devastating disease and over $200 million for research and advocacy efforts. The trial, known as CENTAUR (Combination of Phenylbutyrate and Tauroursodeoxycholic Acid), was funded in part by Ice Bucket Challenge donations.

ALS affects approximately 16,000 people across the United States, and only four drugs are currently approved to help treat the disease. In ALS, a loss of nerve cells that control movement (motor neurons) leads to progressive muscle weakness. As the disease progresses, people with ALS experience difficulty with movement, speaking, eating, and breathing, and may require interventions such as a tracheostomy to prevent respiratory failure.

The CENTAUR clinical trial found that research participants taking AMX0035 had a significant reduction in disease progression compared to placebo, as measured by the ALS Functional Rating Scale. Notably, enrollment criteria for the study selected 'fast progressors' — a subtype of participants believed to be more likely to show an effect (if there is one) during a trial — by studying a database of over 10,000 people with ALS. In an interview with Neurology Live, study principal investigator Dr. Sabrina Paganoni stated, "These patients are not biologically different from other people with ALS; this was basically a statistical strategy to increase our power to see a treatment effect with a relatively smaller trial." Participants are being invited to enroll in an open-label extension study, providing everyone with access to the study drug and an extended follow-up period. 

Prior research studies have found that sodium phenylbutyrate improved outcomes in an ALS mouse model and provided neuroprotection, while tauroursodeoxycholic acid reduced endoplasmic reticulum stress and prevented neurotoxicity. Both tauroursodeoxycholic acid and sodium phenylbutyrate were each individually tested in people with ALS, but there was no larger-scale follow-up of the compounds until now. Amylyx Pharmaceuticals found the combination reduced cell death, prompting the current trials in ALS as well as Alzheimer’s disease.