Investigational ALS drug prolongs patient survival in clinical trial

BOSTON – An experimental medication that was recently shown to slow the progression of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, has now demonstrated the potential to also prolong patient survival. The findings come from a clinical trial conducted 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. Amylyx developed AMX0035, the investigational neuroprotective therapy evaluated in the CENTAUR trial and designed to reduce the death and dysfunction of motor neurons.

ALS, a degenerative condition without a cure, attacks brain and spinal cord nerve cells to progressively affect individuals’ ability to move, speak, eat and even breathe. The new results, reported in the journal Muscle and Nerve, provide additional proof of the benefits that patients with ALS may experience when taking the oral drug called AMX0035, which is a combination of sodium phenylbutyrate and taurursodiol. These components target oxidative stress within nerve cells’ energy-producing mitochondria and protein-processing endoplasmic reticulum to help prevent neurodegeneration.

In the CENTAUR trial, 137 participants with ALS were randomized two-to-one to receive AMX0035 or placebo. Recently, investigators demonstrated that AMX0035 slowed ALS disease progression over six months, with impacts on various activities of daily living such as a patient’s ability to walk, talk, use utensils or swallow food. Patients who completed CENTAUR were eligible to participate in an open-label extension (in which all patients received AMX0035) aimed at assessing the long-term safety and efficacy of the medication.

Investigators’ nearly three-year survival analysis incorporated all participants who enrolled in CENTAUR, whether they continued long-term treatment with AMX0035 in the open-label extension or not. The team found that participants originally randomized to receive AMX0035 lived for a median of 6.5 months longer than those originally randomized to receive the placebo.

“These findings are an important step forward because, in this trial, early treatment with AMX0035 was associated with longer survival in people with ALS,” said the study’s leader Sabrina Paganoni, MD, PhD, investigator at the Healey & AMG Center for ALS and assistant professor of Physical Medicine and Rehabilitation at Harvard Medical School and Spaulding Rehabilitation Hospital. “These results provide substantial evidence supporting the role of AMX0035 for the treatment of ALS. Next steps will depend on ongoing discussions with regulatory agencies.”

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 Harvard Medical School, added: “This is one of the first studies to show effect on both function and survival. We are hopeful that this is just the beginning of many new treatments for ALS.”

The trial was a collaboration among the Healey & AMG Center, Amylyx Pharmaceuticals, Inc., the ALS Association, ALS Finding a Cure, and academic partners such as the Northeast ALS Consortium (NEALS), the MGH Biostatistics Center, and the Barrow Neurological Institute.

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 clinical research, along with encouraging the opportunity to influence and improve the ALS research process.