Sabrina Paganoni, MD, PhD

“We know that there are many different primary insults that cause ALS, but we also know that many of them converge on common mechanisms, including the activation of mitochondrial pathways and endoplasmic reticulum-dependent pathways.”

CENTAUR trial lead investigator Sabrina Paganoni, MD, PhD, told 

 in a recent interview that the results of the phase 2/3 assessment of AMX0035 were a milestone moment in the treatment of patients with amyotrophic lateral sclerosis (ALS). The agent, developed by Amylyx Pharmaceuticals, is a combination of sodium phenylbutyrate–taurursodiol.

Notably, 77% of patients assessed in the trial were already on an approved ALS therapy, either riluzole (n = 96), edaravone (Radicava, MT Pharma; n = 46), or both (n = 38), during and/or before trial entry. When Paganoni and colleagues conducted sensitivity analyses to correct for this, their findings suggested that AMX0035 had a clinical benefit independent of these other treatments with a well-tolerated safety profile. This, she explained, implies that the agent can be successfully combined with these agents to offer patients additional benefit.

Paganoni detailed the combination that comprises AMX0035 and the pathways being targeted, as well as the changes observed in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores and how those changes translate to improvements in patients’ daily lives.

REFERENCE
Paganoni S, Macklin EA, Hendrix S, et al. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. 

. 2020;383:919-930. doi: 10.1056/NEJMoa1916945

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The investigator at the Healey & AMG Center for ALS detailed the combination of AMX0035 and other agents and how ALSFRS-R scores translate to daily life.

Sabrina Paganoni, MD, PhD: A Combination Approach to ALS

“Patients tell us that their number one desire is to be able to maintain physical function for as long as possible. For example, they want to continue to be able to walk or to continue to be able to negotiate stairs. They want to be able to use their hands so they can cut their food, or type emails, or use the phone. That’s exactly what we measured in the trial.”

The full dataset from the phase 2/3 CENTAUR trial (NCT03127514) of the investigational combination therapy AMX0035 suggests that the sodium phenylbutyrate–taurursodiol agent slows functional decline in patients with amyotrophic lateral sclerosis (ALS) compared with placebo. Analysis of the change from baseline revealed a 2.92-point higher mean Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score for the AMX0035 group (

Lead investigator Sabrina Paganoni, MD, PhD, investigator, Healey & AMG Center for ALS, Massachusetts General Hospital, told 

in this interview that these findings for the Amylyx Pharmaceuticals agent mark a milestone moment for the ALS community. Paganoni offered insight into the findings of the trial, and what sensitivity analyses suggest about its possible role in the landscape of treatment.

She shared her perspective on the level of cooperation that ultimately resulted in the CENTAUR, noting that members of the ALS community came from all corners to fund and design the study. CENTAUR received the ALS ACT grant and was funded in part by the ALS Ice Bucket Challenge, in addition to support from a number of advocacy and clinician organizations.

The investigator at the Healey & AMG Center for ALS spoke to the newly released findings of the phase 2/3 trial of the investigational combination ALS agent AMX0035.

Sabrina Paganoni, MD, PhD: Takeaways From the CENTAUR Trial of AMX0035

“For us, as investigators, but also as clinicians—I follow patients in the clinic and meet their families&mdash;it’s incredibly exciting to think that we are contributing to a project that could actually substantially impact people’s lives.”

For clinicians like Sabrina Paganoni, MD, PhD, who participate in clinical studies, there’s a rewarding part of the work when an effective therapy gets approval. Particularly so when the disease being treated is a fatal one, such as amyotrophic lateral sclerosis (ALS). Paganoni, who is the co-director of the Neurological Clinical Research Institute at Massachusetts General Hospital, has been involved in the development of an agent that has shown some promise in ALS: Amylyx Pharmaceuticals’ AMX0035.

The drug is a combination of sodium phenylbutyrate (PB) and tauroursodeoxycholic acid (TUDCA), and recent data from the phase 2 CENTAUR trial (NCT03127514) showed that it resulted in a statistically significant (

<.05) slowing of disease progression in patients with ALS.

 The full results of the study are expected to publish before the end of the year, but in the meantime, Paganoni offered her perspective to 

She spoke to what might be the next steps for AMX0035 on its road toward the FDA and what her experience as part of the CENTAUR trial was like. She also offered some perspective on what she’s expecting and hoping to happen in ALS care over the next few years.

Amylyx Pharmaceuticals announces AMX0035 demonstrated statistically significant treatment benefit for people with ALS in the CENTAUR trial [news release]. Cambridge, MA. Amylyx Pharmaceuticals. December 17, 2019. Accessed August 19, 2020. businesswire.com/news/home/20191217005248/en/Amylyx-Pharmaceuticals-Announces-AMX0035-Demonstrated-Statistically-Significant.

The co-director of the Neurological Clinical Research Institute at Massachusetts General Hospital offered her perspective on the expected developments for ALS care in next few years, and where AMX0035 might fit in that landscape.

Sabrina Paganoni, MD, PhD: AMX0035 and the Future of ALS Care

“The randomized trial was relatively short, only 6 months, and so it’s very important to consider its results in combination with the open-label extension that provides longer term outcomes&shy;&shy;.”

Two agents, sodium phenylbutyrate (PB) and tauroursodeoxycholic acid (TUDCA), make up the investigational combination approach to amyotrophic lateral sclerosis (ALS) from Amylyx Pharmaceuticals. PB has been used to treat urea cycle disorders and TUDCA to treat dissolve gallstones and some forms of liver disease for some time.

The combination was recently investigated for the treatment of ALS in the phase 2 CENTAUR trial (NCT03127514), which included more than 100 patients and was conducted by Sabrina Paganoni, MD, PhD, co-director, Neurological Clinical Research Institute, Massachusetts General Hospital, and colleagues. The full results of the study are expected to publish before the end of the year, but in the meantime, Paganoni provided her insight to 

Paganoni discussed her takeaways from the positive top-line data to this point and why this trial was so important for the ALS community. Additionally, she noted how the ongoing open-label extension data will continue to inform the group about AMX0035 in this population, and what the extension will be observing in the study population.

The co-director of the Neurological Clinical Research Institute at Massachusetts General Hospital spoke to findings of the phase 2 CENTAUR trial of AMX0035 in amyotrophic lateral sclerosis.

Sabrina Paganoni, MD, PhD

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