BOSTON- The HEALEY ALS Platform Trial conducted by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital in conjunction with the Northeast ALS Consortium (NEALS) is a trial in which multiple investigational products are tested and evaluated simultaneously to accelerate development potential new therapies for people with amyotrophic lateral sclerosis (ALS). Drug candidates that enter the platform’s trial are chosen by a panel of expert ALS scientists and members of the Healey & AMG Center’s Scientific Advisory Board. The Healey & AMG Center for ALS at Mass General and Calico Life Sciences LLC recently signed an agreement to work together to test ABBV-CLS-7262 in the HEALEY ALS Platform Trial.
ABBV-CLS-7262 targets eIF2B, a key regulator of the Integrated Stress Response (ISR), a pathway activated in people with ALS. In neurons exposed to cellular stressors, ISR inhibition by ABBV-CLS-7262 restores protein synthesis and dissolves stress granules containing preformed TDP-43. This effect of ABBV-CLS-7262 is of clinical interest because TDP-43-containing stress granules are thought to lead to TDP-43 inclusions, a hallmark of ALS pathology. ABBV-CLS-7262 is currently in a Phase 1b study in ALS patients (NCT04948645).
ABBV-CLS-7262 is an investigational drug developed by Calico in collaboration with AbbVie and not yet approved for use in any country. Calico is a research and development company founded by Alphabet that focuses on understanding the biology that controls human aging. With AbbVie, they collaborate to discover and develop potential new therapies for patients with age-related diseases, including neurodegenerative disorders.
“We look forward to testing ABBV-CLS-7262 as another investigational ALS product in the HEALEY ALS platform trial. It is exciting to be able to test multiple products at once in hopes of ‘accelerating the path to more treatments for ALS,’ says 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 the MGH, and Julieanne Dorn Professor of Neurology at Harvard Medical School.
“We are excited to add ABBV-CLS-7262 to the HEALEY ALS platform trial. The Therapy Review Board assessed ABBV-CLS-7262 for inclusion in the platform trial based on the quality of Calico and AbbVie science and preparation of the platform. -form and we can’t wait to have them on board,” says Sabrina Paganoni, MD, PhD, physician-scientist at the Healey & AMG Center and co-principal investigator.
The platform trial is testing several other products, including: a) zilucoplan, a small macrocyclic peptide inhibitor of complement component 5 [C5]b) verdiperstat, a brain-penetrating myeloperoxidase enzyme inhibitor, c) CNM-Au8, a cellular energy nanocatalyst, d) pridopidine, a highly selective oral Sigma-1 receptor (S1R) agonist, and e) trehalose, a weighty disaccharide that affects autophagy and lysosomal pathways
For trial updates, please join our weekly webinars on the Healey ALS platform.
Watch this video for more information on the mechanism of action behind ABBV-CLS-7262.
Background to ALS
Amyotrophic lateral sclerosis, ALS, is the most common progressive motor neuron disease in adults, affecting about 30,000 people in the United States and about 500,000 people worldwide. ALS causes progressive degeneration of motor neurons, resulting in progressive muscle weakness and atrophy. There are currently few FDA-approved therapies for the treatment of ALS – riluzole, edaravone (IV and oral formulation), and Nuedexta.
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 seek lifesaving therapies for everyone affected by ALS. Launched in November 2018, the Healey Center relies on a global network of scientists, doctors, nurses, caregivers, people with ALS and families working together to accelerate the pace of discovery and development of ALS therapies.
Under the leadership of Merit Cudkowicz, MD and a Scientific Advisory Board of international experts, we are reimagining how to develop and test the most effective therapies to treat disease, identify cures, and ultimately prevent it.
The key to our success lies in our tightly integrated research and clinical efforts, encouraging opportunities to address the challenges our patients face every day in our laboratories, focusing research on finding solutions that will make a meaningful difference to our patients without delay. Our collaborative efforts are helping to design more efficient and effective clinical trials while expanding access to these trials for people with ALS.