Healey ALS MyMatch Program Advances with Completion of First Trial and Selection of Tiziana's Foralumab
Key Insights
The Sean M. Healey & AMG Center for ALS (search) completed enrollment of 41 participants in its first biomarker-driven MyMatch trial testing repurposed digoxin for ALS (search) treatment.
Tiziana Life Sciences was selected to enter the program with intranasal foralumab, a fully human anti-CD3 (search) monoclonal antibody targeting neuroinflammation in ALS (search) patients.
The ALS (search) MyMatch program uses personalized medicine approaches with genetic and biofluid biomarkers to match patients to optimal experimental treatments in early-phase trials.
The Sean M. Healey & AMG Center for ALS (search) at Massachusetts General Hospital has achieved two significant milestones in its innovative ALS (search) MyMatch program, completing enrollment for its first biomarker-driven trial while selecting Tiziana Life Sciences to advance intranasal foralumab into clinical testing.
ACACIA Trial Reaches Full Enrollment
The ACACIA Trial (ClinicalTrials.gov identifier: NCT07047209), a Phase 2a open-label study of oral digoxin, successfully enrolled 41 participants across three clinical sites over four months. The trial represents the first completed enrollment under the ALS (search) MyMatch umbrella, testing digoxin as a repurposed experimental medication for ALS treatment.
Digoxin, traditionally used for heart conditions including heart failure and irregular heartbeats, emerged as a candidate through extensive preclinical screening. Research from the Wainger Lab evaluated thousands of drugs in ALS (search) models using neurons derived from induced pluripotent stem cells (iPSCs), with digoxin demonstrating reduced ALS features in both iPSC-derived neurons and mouse ALS models.
"The initiation of Healey ALS (search) MyMatch – ACACIA Trial evaluating digoxin is an important step forward in our efforts to deepen our understanding of the mechanisms that drive ALS and how digoxin may influence these disease processes," said Dr. Brian Wainger, Associate Professor of Neurology and Anesthesiology at Harvard Medical School and Co-Principal Investigator of the ACACIA Trial.
Tiziana's Foralumab Selected for Program Entry
The ALS (search) MyMatch Therapy Evaluation Committee selected Tiziana Life Sciences to develop a biomarker-driven Phase 2a clinical trial for intranasal foralumab, partially funded by the ALS Association (search)'s Hoffman ALS Clinical Trial Awards Program. The trial will be led by Principal Investigators Suma Babu, MBBS, MPH, and James Berry, MD, MPH, Chief of the Division of ALS and Motor Neuron Diseases at Mass General Brigham.
Foralumab is a fully human anti-CD3 (search) monoclonal antibody designed to stimulate T regulatory cells through nasal spray administration. The treatment targets neuroinflammation and immune dysregulation, particularly T-cell dysfunction and microglial activation, which are increasingly recognized as key drivers of ALS (search) disease progression.
Preclinical and clinical evidence indicates that nasally administered foralumab stimulates regulatory T cells in cervical lymph nodes, which then migrate to the central nervous system to suppress pathogenic inflammation and restore microglial homeostasis.
Personalized Medicine Approach
The ALS (search) MyMatch program addresses a critical gap in ALS research by focusing on early-phase studies that identify target populations, determine optimal dosing, and demonstrate target engagement. The program utilizes genetic, biofluid, imaging and other biomarkers to match participants to appropriate experimental treatments, including measurement of cerebrospinal fluid levels and determination of central nervous system penetration.
"ALS (search) MyMatch is designed to increase efficiency by accelerating trial startup and shortening the time for participants to screen and enter a trial," said Merit Cudkowicz, MD, Director of the Healey & AMG Center and Executive Director of the Mass General Brigham Neuroscience Institute.
The program incorporates innovative initiatives from the Network of Excellence in Clinical Trials (NEALS) Consortium, including use of a single Institutional Review Board, highly trained research sites, and a patient advisory committee to enable rapid enrollment and high-quality data collection.
Multi-Site Collaborative Framework
ALS (search) MyMatch operates as a multi-site initiative currently encompassing four high-enrolling ALS research centers: Mass General in Boston, University of Minnesota in Minneapolis, Northwestern University in Evanston, and Nova Southeastern University in Fort Lauderdale. The program has partnered with the Acceleration Centers of Enrollment (ACE) program to expedite startup and recruitment at study centers.
"We are thrilled to finalize design and move towards next steps of trial conduct of this multi-site trial with Tiziana Life Sciences," stated Dr. Babu. "The trial will use cellular and biofluid biomarkers alongside advanced brain imaging to better understand how the drug works in the brain and to group participants in the trial based on their unique disease profile."
The foralumab trial represents a continuation of groundbreaking preclinical work by Howard Weiner, MD, Professor of Neurology at Harvard Medical School, whose research has laid the foundation for foralumab's translation into clinical trials for multiple neurological diseases including multiple sclerosis, Alzheimer's disease, and multiple system atrophy.
"Based on the effect of foralumab in ALS (search) models and in MS and Alzheimer's disease, my team and I are hopeful that foralumab will affect disease progression in ALS," said Dr. Weiner.
Each trial in the ALS (search) MyMatch program is named after a tree to symbolize hope and the deep scientific roots underlying the research. The trials are designed to generate clear data under efficient processes while de-risking and guiding decisions for later-phase trials, including determining optimal dosage and identifying target populations for broader phase 2/3 studies.