Sabrina Paganoni, MD, PhD, Massachusetts General Hospital, Harvard Medical School, Boston, MA, shares the results of a long‐term survival analysis of participants in the CENTAUR trials (NCT03127514, NCT03488524) of AMX0035 for amyotrophic lateral sclerosis (ALS). Results demonstrated that AMX0035 was safe, tolerable, and associated with improved outcomes in people with ALS, such as slowing of functional decline and longer survival compared to placebo. This interview took place during the American Academy of Neurology (AAN) 2021 Annual Meeting.
Transcript (edited for clarity)
I’m really excited to present at the American Academy of Neurology Annual Meeting very soon about AMX0035 and the CENTAUR trial. AMX0035 is a new investigational product that’s being tested for the treatment of ALS. The product is manufactured by Amylyx Pharmaceuticals and is a combination of two compounds known as sodium phenylbutyrate and TURSO. Each of these compounds has a different activity in nerve cells...
I’m really excited to present at the American Academy of Neurology Annual Meeting very soon about AMX0035 and the CENTAUR trial. AMX0035 is a new investigational product that’s being tested for the treatment of ALS. The product is manufactured by Amylyx Pharmaceuticals and is a combination of two compounds known as sodium phenylbutyrate and TURSO. Each of these compounds has a different activity in nerve cells. They act on endoplasmic reticulum stress and mitochondrial dysfunction, respectively. They were already known in the ALS space because the individual compounds had been previously tested in the lab and in early phase clinical trials, because the individual compounds were noted to have neuroprotective properties in the lab.
When Amylyx Pharmaceuticals combined the two, they noticed an even greater neuroprotective effect of the combination in lab experiments. So, the CENTAUR trial was the first time that we tested the combination of the two in a specific ratio in people with ALS. The CENTAUR trial was a randomized, double-blind, placebo-controlled trial that included 137 participants with ALS. The trial was conducted at 25 sites of the NEALS consortium in the US. It was designed and conducted as a fantastic collaboration between industry and academia and the coordination center was at the Healey Center for ALS at the Massachusetts General Hospital and the Barrow Neurological Institute. It was also a great collaboration with the patient community and foundations, and really a great example of what we can accomplish when we all work together.
The goals of the trial were to evaluate both the safety and efficacy of AMX0035 in people with ALS. Efficacy was measured by collecting the functional rating scale, the ALSFRS-R, with the goal of measuring function, and we also captured long-term survival. The main results are that AMX0035 was safe, tolerable, and associated with improved outcomes in people with ALS who participated in this trial. In terms of ALS outcomes, we noticed slowing of functional decline among participants randomized to AMX0035 relative to placebo, and longer survival.
So let me tell you a little bit more about these two efficacy results. At the end of the 6-month placebo-controlled trial, the participants who were assigned to AMX0035 scored higher on the ALS Functional Rating Scale compared to placebo, and that indicates that they retained physical functions for longer. In terms of survival, we followed all trial participants long-term for up to three years after the original randomization. And we found that the risk of death was 44% lower among participants originally randomized to AMX0035 compared with placebo. So I think that, overall to summarize, the drug was safe and appears to provide significant functional and survival benefits for people with ALS.