Investigational ALS drug generates promising clinical trial results

BOSTON – An experimental medication slows the progression of the neurodegenerative disease called amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, according to recently released results from a clinical trial run by investigators at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) and Amylyx Pharmaceuticals, Inc., the company that manufactures the medication. The findings, reported in the New England Journal of Medicine, offer hope that a treatment may one day be available for patients with ALS, a fatal condition with no cure that attacks the nerve cells in the brain and the spinal cord to progressively hinder individuals’ ability to move, speak, eat, and even breathe.

Called AMX0035, the oral medication is a combination of two drugs, sodium phenylbutyrate and taurursodiol, that each target a different cell component important for protecting against nerve cell death. 

In the CENTAUR trial, 137 participants with ALS were randomized in a two-tone ratio to receive AMX0035 or placebo. Over six months, participants who were treated with AMX0035 had better functional outcomes than those treated with placebo as measured by the ALS Functional Rating Scale (ALSFRS-R), a questionnaire that evaluates several activities of daily living such as a patient’s ability to walk, hold a pen or swallow food.

“The participants treated with AMX0035 demonstrated a significant slowing of ALS disease progression as measured by the ALSFRS-R. This is a milestone in our fight against ALS,” said Sabrina Paganoni, MD, PhD, principal investigator of the CENTAUR study, investigator at the Healey & AMG Center for ALS at MGH, and assistant professor of PM&R at Harvard Medical School (HMS) and Spaulding Rehabilitation Hospital. Paganoni noted that the trial involved a partnership between industry, foundations such as the ALS Association and ALS Finding a Cure and academia, with input from world-renowned leaders in neurology and drug development.

Senior author Merit Cudkowicz, MD, director of the Healey & AMG Center for ALS at MGH, chief of Neurology at MGH, and the Julieanne Dorn Professor of Neurology at HMS, commented, “Amylyx took a novel approach to the problem of motor nerve cell dysfunction. With guidance from our team and in collaboration with our colleagues in the Northeast ALS Consortium (NEALS), Mass General Biostats and the Barrows Neurological Institute, the clinical trial moved forward quickly and carefully. We are proud of this important study. We are also very thankful to the participants and their families for their key role in advancing research.” 

In 2015, Amylyx co-founders and co-CEOs Joshua Cohen and Justin Klee were introduced to Cudkowicz by Rudy Tanzi, PhD, co-director of the McCance Center for Brain Health at MGH—who would eventually help co-found Amylyx and lead its scientific advisory board—and shared their vision for AMX0035. The teams decided that MGH’s expertise in designing and leading clinical trials and Amylyx’s potential treatment would make for a great collaboration. Cudkowicz introduced them to Paganoni and to the science advisory committee for NEALS, a trial network Cudkowicz co-founded. Soon after, the CENTAUR Trial came to fruition and sites throughout the NEALS consortium began enrolling patients.

“Today’s news builds upon the progress we have made in ALS research,” said Cohen. “This experimental medicine has demonstrated that it can help patients retain their physical function, which is an incredible feat given the debilitating nature of this disease. It is our hope that AMX0035 will one day be available for patients and we are committed to making that a reality.”

"Patients and their families do not have time to wait," said Klee. "People with ALS progressively lose their ability to function and care for themselves, so we want to do everything we can to help them slow down this devastating disease. We will be working with the FDA to determine next steps and the path for patients to gain access to AMX0035. We’ll continue to share our plans with the community as they develop."

An Open Label Extension trial, in which all patients in the study have been offered AMX0035, is ongoing to assess the medication’s long-term impact.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2020, Mass General was named #6 in the U.S. News & World Report list of "America’s Best Hospitals."

About the Sean M. Healey & AMG Center for ALS at Mass General
At the Sean M. Healey & AMG Center for ALS at Mass General, we are on a quest to discover life-saving therapies for all people who are affected by ALS. Launched in November 2018, we are a diverse group of researchers and clinicians determined to accelerate the pace of ALS therapy development.

Under the leadership of Merit Cudkowicz, MD, chief of Neurology, and a Science Advisory Council of international experts, we partner with other experts around the globe to reimagine how to develop the right novel therapies for the right people at the right time. We are grounded in our strong belief in the partnership between people with ALS, caregivers and our team. Together we can design more efficient and more effective clinical trials and broaden access for people with ALS.

For more information, please email healeycenterforals@mgh.harvard.edu and visit the center’s website https://www.massgeneral.org/neurology/als/.

About the Northeast ALS Consortium
The Northeast ALS Consortium (NEALS) is an international, independent, non-profit group of 134 research sites around the world that collaboratively conduct clinical research in Amyotrophic Lateral Sclerosis (ALS) and other motor neuron diseases. The mission of NEALS is to translate scientific advances into new treatments for people with ALS and motor neuron disease as rapidly as possible. The NEALS member sites are committed to the principles of open scientific communication, peer review, and democratic governance of the Consortium’s organization and activities. Governed by an Executive Committee, the Consortium’s research activities are advised by an experienced Scientific Advisory Board. The NEALS Science Advisory Board also regularly guides academic and industry partners on ALS targets, trial design, and conduct.

NEALS is dedicated to educating people with ALS on clinical research and therapy development and empowering them to be advocates for ALS clinical research,

About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $1 billion and comprises more than 8,500 researchers working across more than 30 institutes, centers and departments. In August 2020 the MGH was named #6 in the nation by U.S. News & World Report in its list of "America’s Best Hospitals."