Healey & AMG Center announces top line results in ALS platform trial with CMN-Au8

BOSTON – The HEALEY ALS Platform Trial led by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) today announced topline results in adults with amyotrophic lateral sclerosis (ALS) from Regimen C evaluating CMN-Au8, developed by Clene Nanomedicine, Inc., a suspension of gold nanocrystals to enhance neuronal energy production and utilization.

The HEALEY ALS Platform Trial was designed to accelerate the development of breakthrough treatments for persons with ALS by testing multiple drugs using a shared infrastructure. CMN-Au8 was one of the first three investigational treatment regimens tested using this innovative paradigm.

The primary endpoint was not met; there was not a statistically significant or clinically meaningful slowing of disease progression as measured by ALS Functional Rating Scale-Revised (ALSFRS-R, a 12-item functional activity scale) slope change adjusted by mortality across the combined CNM-Au8 doses at 24 weeks (2% slowing, 95% CI: -20% to +19%). The key secondary endpoints including a combined assessment of function and survival (CAFS) and change in slow vital capacity (SVC) were also not met at week 24.

The prespecified exploratory analyses of the secondary survival endpoint demonstrated a >90% reduction in risk of death alone or risk of death/permanently assisted ventilation at 24 weeks, when adjusting for baseline imbalances in risk (p=0.028 to p=0.075, unadjusted for multiple comparisons) with the CNM-Au8 30 mg dose. These survival results were statistically consistent for the 30 mg dose between the regimen only and full analysis sets, which included shared placebo from other regimens participating in the HEALEY ALS Platform trial (Regimens A, B, and D). The number of events were small in all groups. A survival benefit was not observed among participants randomized to 60 mg CNM-Au8. 

The full analyses, including data on measures of speech function, biomarkers of neurodegeneration and further results from an ongoing open-label extension, are expected later in 2022. The open label extension study will continue at 30 mg/day.

“Though we did not achieve success on the primary and key secondary outcomes during the 24-week placebo-controlled period of this trial, the potential survival benefit at 30 mg/day dose is encouraging and warrants continued follow up in the open-label extension study. In addition, the digital and fluid biomarker results will provide additional insights into disease biology and drug effects for CNM-Au8," said Merit Cudkowicz, MD, MSc, principal investigator and sponsor of the HEALEY ALS Platform Trial, director of the Sean M. Healey & AMG Center for ALS, chief of the Department of Neurology at MGH, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “We are thankful to the many people who participated in this study. We will learn from these results and continue to use these data to inform future advances in ALS trial design.”

“This trial represents an important contribution to ALS research.  We remain committed to using the data to advance ALS science and will use our experience with the trial to understand the biology of CNM-Au8, investigate ALS mechanisms, and find novel therapies for people living with ALS,” said James D. Berry, MD, MPH, Director of the Neurological Clinical Research Center at MGH, Winthrop Family Scholar in ALS Sciences, Averill Healey Endowed Chair in ALS and co-lead investigator of the CNM-Au8 regimen.

“We would like to extend our sincere gratitude to all the participants in the CNM-Au8 regimen who committed their invaluable time and hope in the trial as well as the NEALS investigators and study staff who dedicated their effort and expertise," says Nicholas J. Maragakis, MD, Director of the Johns Hopkins ALS Clinical Trials Unit, and co-lead investigator of the CNM-Au8 regimen. “Participants' involvement in the trial contributed greatly to ALS research by providing substantial clinical and biomarker data that will help us better understand ALS disease mechanisms and the role of cellular catalysts in people living with ALS.”

This study was made possible by funding from The AMG Charitable Foundation, Tackle ALS, The ALS Association, ALS Finding A Cure®, ALS One, The Muscular Dystrophy Association, Arthur M. Blank Family Foundation, I AM ALS, Tambourine ALS Collaborative, and countless individuals who support the HEALEY ALS Platform Trial.

Background on ALS
Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 500,000 people worldwide. ALS causes the progressive degeneration of motor neurons, resulting in progressive muscle weakness and atrophy. There are few FDA therapies currently approved for treating ALS—riluzole, edaravone (IV and oral formulations), and Nuedexta.

About the Sean M. Healey & AMG Center for ALS at MGH
At the Sean M. Healey & AMG Center for ALS at MGH, we are on a quest to discover life-saving therapies for all individuals affected by ALS. Launched in November 2018, the Healey Center leverages a global network of scientists, physicians, nurses, caregivers, people with ALS and families working together to accelerate the pace of ALS therapy discovery and development.

Under the leadership of Merit Cudkowicz, MD, MSc and a Science Advisory Council of international experts, we are reimagining how to develop and test the most promising therapies to treat the disease, identify cures, and ultimately, prevent it.

The key to our success is our tightly integrated research and clinical efforts, encouraging opportunities to bring the challenges our patients face every day into our laboratories, focusing investigations on finding solutions that will make a meaningful difference to our patients without delay. Our collaborative efforts lead to design of more efficient and effective clinical trials while broadening access to these trials for people with ALS.

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 is the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprised of more than 9,500 researchers working across more than 30 institutes, centers, and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report 
list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.