This study is really the first comprehensive platform for ALS drug development, where a central infrastructure is shared between a variety of investigational products, each tested using a common protocol and compared to a shared placebo cohort.

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

BOSTON – A new paper in Annals of Neurology describes the approach, structure, and launch of the HEALEY ALS Platform Trial– the first platform trial for amyotrophic lateral sclerosis (ALS) designed to accelerate the development of effective and breakthrough treatments for people with the illness.

“This study is really the first comprehensive platform for ALS drug development, where a central infrastructure is shared between a variety of investigational products, each tested using a common protocol and compared to a shared placebo cohort,” says first author and co-principal investigator Sabrina Paganoni, MD, PhD, co-director of the Massachusetts General Hospital (MGH) Neurological Clinical Research Institute (NCRI), physician scientist at the Healey & AMG Center for ALS at Mass General, and assistant professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital.  “Due to this design, people living with ALS who participate in this trial have a greater chance of receiving an active treatment.”

Under the leadership of Paganoni and principal investigator Merit Cudkowicz, MD, MSc, director of the Sean M. Healey and AMG Center for ALS, chief of Neurology at MGH and the Julieanne Dorn Professor of Neurology at Harvard Medical School, the HEALEY ALS Platform Trial enrolls patients across a network of more than 50 coordinated sites of the NEALS Consortium nationwide. The trial simultaneously evaluates several treatments on an ongoing basis. 

“The trial has several important scientific goals as we are collecting a number of novel biomarkers and outcome measures which could provide more efficient readouts not only for this trial for the entire ALS clinical trial landscape,” says Cudkowicz. “Further, we are creating an approach that ensures data sharing and sample sharing from the growing placebo cohort where we hope we can contribute to our understanding of the science behind ALS and share the learnings in a collaborative manner.”

Currently, the HEALEY ALS Platform Trial has completed enrollment in its first four trial arms and testing of a fifth investigational product has already begun. “An important feature of the trial is that it will be evergreen, meaning that we intend to always have multiple investigational products available to new participants,” says Paganoni. The team is working with more industry collaborators to create new treatment spots in 2022 with a plan for many more after that.

Since its inception in Summer 2020, more than 800 patients have enrolled in the HEALEY ALS Platform trial, with about 160 participants assigned to the first four trial arms. Results from these first four studies are expected later in 2022. “Because of the platform nature of the study and the use of a shared placebo group, the active to placebo ratio is very favorable for participants, three to one in favor of receiving an active drug,” says Paganoni. “That is simply not possible with traditional stand-alone trials ,” she says. The trial design allows all participants to receive active treatment as part of a long-term Open Label Extension (OLE) after six months of randomized, placebo-controlled trial participation. In addition to granting access to active drug, the OLE will provide important scientific data about the long-term safety and efficacy of the investigational products tested in the trial.

The HEALEY ALS Platform Trial has invigorated the ALS clinical trials landscape, and there has been resounding support from the patient community. Enrollment has been exceeding expectations which is remarkable considering that the trial’s launch coincided with the COVID-19 pandemic.

“We are grateful to the members of our Patient Advisory Committee who have been working with us to design a patient-centric trial with more access opportunities,” says Paganoni. “This trial would not be possible without the generous contributions of hundreds of people with ALS and their families and supporters who decided to devote their time and efforts to ALS research to benefit the entire ALS scientific and patient family during these challenging pandemic times.”


Jump-started by a grant from the HEALEY & AMG Center for ALS, the HEALEY ALS Platform Trial is funded by the AMG Charitable Foundation, Tackle ALS, The ALS Association, ALS Finding A Cure, Muscular Dystrophy Association, ALS One, Arthur M. Blank Family Foundation, I AM ALS, Tambourine ALS Collaborative and many other community fundraising initiatives and donors.

Other authors of the study include James D. Berry MD, MPH, Melanie Quintana PhD, Eric Macklin PhD, Benjamin R. Saville PhD, Michelle A. Detry PhD, Alexander V. Sherman MSc, Hong Yu MS, Kristin Drake MBA, Jinsy Andrews MD, Jeremy Shefner MD, PhD, Lori B. Chibnik PhD, MPH and Matteo Vestrucci PhD as well as study staff and site investigators from the HEALEY ALS Platform Trial Study Group.

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 2021, Mass General was named #5 in the U.S. News & World Report list of "America’s Best Hospitals."

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 currently three FDA therapies approved specifically for treating ALS symptoms—riluzole, nuedexta and edaravone.

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 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 and a Science Advisory Council of international experts, we are reimagining how to develop and test the most effective 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 are designing more efficient and effective clinical trials while broadening access to these trials for people with ALS.