An investigational oral therapy called PrimeC was found to be safe and well tolerated in people with amyotrophic lateral sclerosis (ALS), according to results published on Mar. 16 from a phase 2b clinical trial led by researchers at Mass General Brigham Neuroscience Institute and Barrow Neurological Institute.
ALS is a progressive neurodegenerative disease that leads to the loss of motor neurons and increasing muscle weakness. The new findings are important because there are limited treatment options for ALS, which is typically fatal.
The multicenter PARADIGM study randomized 68 participants to receive either PrimeC or placebo for six months, followed by a 12-month open-label extension where all participants received PrimeC. While drug-related adverse events were more common among those taking PrimeC compared to placebo, most side effects were mild to moderate and temporary. Exploratory findings suggested that those who took PrimeC had better functional outcomes, particularly in speech and swallowing, as measured by the ALS Functional Rating Scale Revised score. At six months, participants on PrimeC scored higher than those on placebo, and after eighteen months, the difference increased further. Early continuous treatment was also linked with a reduced risk of ALS-related complications such as hospitalization, respiratory failure, or death.
Biomarker analyses indicated that patients initially assigned to PrimeC had lower levels of ferritin—a protein involved in iron storage—and lower levels of certain microRNA molecules associated with ALS. There were no significant changes between groups in blood levels of neurofilament light chain.
"The improved functional and biomarker signals we observed support a phase 3 study to evaluate PrimeC's effectiveness and safety in a larger population," said Merit Cudkowicz, MD, MSc, Executive Director of Mass General Brigham Neuroscience Institute and Director of the Sean M. Healey & AMG Center for ALS."The importance of following up on potential therapies that can slow the course of ALS is extraordinarily high for patients and families. We are determined to accelerate the development of therapies for people living with ALS."
Jeremy M. Shefner, MD, PhD, professor of Neurology at Barrow Neurological Institute and corresponding author of the publication said: "What stands out about the PARADIGM study is that multiple clinical endpoints suggest the same level of clinical benefit and that multiple biomarkers are consistent with clinical endpoints." He added: "Together, these findings provide a strong scientific foundation for advancing PrimeC into a Phase 3 trial designed to validate its impact for patients."
