New findings from the CENTAUR trial show that the drug ‘sodium phenylbutyrate–taurursodiol’ (AMX0035) may slow down functional decline in persons living with ALS. The latest results of this multicentre, phase 2 trial were published on September 3rd in the renowned New England Journal of Medicine. These findings are promising, but larger and longer follow-up studies need to confirm the results in a more representative patient cohort.
Over the past decades, more than seventy drugs have been evaluated. Only riluzole and edaravone have shown to modestly improve daily functioning or survival. While the efficacy of AMX0035 appears subtle at this stage, its positive effects are encouraging for the ALS community.
Slower functional decline
AMX0035 consists of a combination of two molecules: tauroursodeoxycholic acid (TUDCA) and sodium phenylbutyrate. Both were previously shown to be safe and well tolerated. The combination of the two drugs is believed to decrease nerve cell damage in people living with ALS. In the CENTAUR trial, 89 participants were randomly assigned to take an oral dose of AMX0035 twice daily for 24 weeks while 48 participants received a placebo treatment (a mock treatment).
Functional decline was measured using the ALSFRS-R scale (ranging from 0 to 48, with higher scores indicating better function). The scale measures a person’s ability in daily function, such as eating and drinking, speech, walking, sleeping and dressing. During the trial, participants who received the placebo drug declined by approximately 1.66 point per month. This is notably more progressive than the average 1.0 point decline normally seen in people living with ALS. Participants who received AMX0035, however, declined on average by 1.24 points (a difference of 0.42 points or a 25% slowing of the progression rate). After 24 weeks of treatment, the absolute mean difference between treatment groups was 2.3 points. This improvement was mainly apparent in fine-motor skills such as handwriting or handling cutlery. Although participants were evaluated for measures such as muscle strength, lung function and/or survival time, the trial was too short to draw definite conclusions.
A follow-up phase 3 trial is now required to confirm these promising results from the CENTAUR trial in a longer study with a larger patient group. The CENTAUR trial was a collaboration between the NEALS network and Amylyx Pharmaceuticals.