Treatment with investigational medication VX15/2503 halts disease-related loss of brain volume and improves its metabolic activity in Huntington’s disease patients, according to a Phase 2 clinical study.
The research, “Clinical Development of VX15/2503 Anti-Semaphorin 4D Antibody as a Potential Treatment for Huntington’s Disease,” was presented by Elizabeth Evans, PhD, as a scientific poster at the 2018 American Academy of Neurology (AAN) Annual Meeting, April 21-27 in Los Angeles, California.
Semaphorin 4D (SEMA4D) is a protein involved in chronic brain inflammation, which may lead to neurodegeneration. This protein also halts neural development, increases cell death, and disrupts the blood-brain barrier, which serves as a control point for what can enter the brain and can contribute to neurodegeneration.
VX15/2503, an antibody developed by Vaccinex, blocks the activity of SEMA4D and prevents brain inflammation. The potential treatment also induces the maturation of specific cells that repair the loss of a protective layer of nerve fibers, called myelin.
Preclinical results in animal models showed that VX15/2503 could protect against the loss of brain volume, a hallmark of Huntington’s disease, prevented spatial memory loss, and suppressed anxiety-like behaviors.
The SIGNAL trial (NCT02481674) is a Phase 2, double-blind, placebo-controlled trial to assess the safety, tolerability and effectiveness of VX15/2503 in Huntington’s patients with late prodromal (before clinical diagnosis) and early manifest disease. The trial is recruiting, and expects to enroll a total of 240 participants.
The study’s main objectives include determining the effect of VX15/2503 on brain volumes using magnetic resonance imaging (MRI), and FDG-PET scans, along with clinical features of the disease, including cognition, motor function, behavior, functional abilities, global function and global measurement of change.
The results presented at the AAN were those of the first group of 36 patients (aka cohort A). Results showed no concerning safety signals after a 12-month intravenous treatment with VX15/2503 and a follow-up of three months. Treated patients also exhibited a trend to stabilize Huntington’s-related reduction in brain volume and improved metabolic activity over placebo.
“Data from Cohort A suggests that treatment with VX15/2503 was well tolerated and appeared to prevent loss of brain volume and restore metabolic activity,” researchers wrote.
The team added that the findings informed the design of a larger group of patients in the SIGNAL trial, whose cognition and motor skills also will be assessed.
VX15/2503 has been granted fast track designation by the U.S. Food and Drug Administration (FDA).