Vaccinex reported top-line results from the Phase 2 double-blind, placebo-controlled SIGNAL trial, evaluating its lead clinical candidate, pepinemab, in patients with early manifest and prodromal Huntington’s disease. Although some benefit was seen in the trial, neither of the co-primary endpoints were reached.
The SIGNAL trial had two sequential Cohorts. The primary outcome of Cohort A was safety and pepinemab appeared to be well-tolerated. Additional data from SIGNAL Cohort A demonstrated that pepinemab treatment results in an increase in FDG-PET signal, a measure of brain metabolic activity, primarily in cortical regions. A decrease in this signal was observed in the placebo group. The design of the subsequent Cohort B was informed by the results of Cohort A and enrolled 265 subjects, 179 early manifest patients (Cohort B1) and 86 late prodromal subjects (Cohort B2) for randomized treatment of at least 18 months duration.
The study had two co-primary endpoints, a family of two cognitive assessments from the Huntington’s Disease Cognitive Assessment Battery and Clinical Global Impression of Change (CGIC). The cognitive assessments reflect changes in planning ability and memory associated with disease progression. Although the study did not meet pre-specified co-primary endpoints, the results of each of the two cognitive assessments demonstrated a strong trend for beneficial change. Similarly, a trend of benefit in CGIC did not show a statistically significant difference between the placebo and pepinemab-treated groups. Pepinemab was well-tolerated.
Vaccinex plans to report additional results, including a broader examination of motor activity and outcomes for a smaller group of 86 prodromal subjects, at the upcoming 2020 Huntington’s Study Group Conference on October 30 and at subsequent medical conferences.
Pepinemab is a humanized monoclonal antibody that binds and blocks the activity of semaphorin 4D (SEMA4D) which is an extracellular signaling molecule that regulates the migration and function of immune and inflammatory cells. Preclinical studies have demonstrated that the biological activities associated with antibody blockade of SEMA4D promote immune cell infiltration into tumors and prevent neurological damage in neuroinflammatory and neurodegenerative disease models.
About Huntington’s Disease
Huntington’s disease is a rare, inherited disease that causes the progressive breakdown (degeneration) of nerve cells in the brain. Huntington’s disease has a broad impact on a person’s functional abilities and usually results in movement, thinking (cognitive) and psychiatric disorders. Huntington’s disease symptoms can develop at any time, but they often first appear when people are in their 30s or 40s.