For Sleep Disturbance in Alzheimer Disease, Cannabinoid-Based IGC-AD1 Shines in Phase 2
An investigational cannabinoid-based treatment for agitation in Alzheimer disease (AD) being developed by IGC Pharma has delivered promising interim phase 2 results, with data showing a clinically and statistically significant reduction in sleep disturbances at 2 and 6-week evaluations among patients receiving the active medication IGC-AD1.
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At week 2, sleep disturbances decreased by approximately 71% (P =.012), and by week 6, the reduction reached approximately 78% (P =.02), as measured by the Neuropsychiatric Inventory Sleep Subscale, according to a company news release.
The findings highlight IGC-AD1’s potential to address a critical yet underrecognized symptom associated with AD—sleep disturbance affects up to 44% of individuals with the disease and is mechanistically associated with disease progression, IGC stressed. The results further reinforce IGC-AD1 ’s potential role as a multi-targeted therapy for addressing neuropsychiatric symptoms associated with AD.
“IGC-AD1’s ability to improve sleep quality in Alzheimer’s patients is very exciting,” Ram Mukunda, CEO of IGC Pharma, said in the statement. “Better sleep is linked to reduced agitation and caregiver distress, as well as [to] slowing cognitive decline and improving overall quality of life.”
Not a Sedative
IGC-AD1, a cannabinoid-based partial CB1 receptor agonist with anti-neuroinflammatory and neuroprotective properties, offers a differentiated mechanism of action compared to existing treatments such as serotonin antagonist and reuptake inhibitor trazodone and orexin inhibitor suvorexant. Both have returned only limited efficacy in placebo-controlled trials, according to IGC, and primarily mask symptoms. If confirmed by larger studies, IGC-AD1 could emerge as a safer, more effective approach to target sleep regulation in AD.
The ongoing phase 2 CALMA (Calming Agitation in Alzheimer's) study is a multi-center, randomized, double-blind, placebo-controlled trial with target enrollment of 164 participants.2 Study inclusion requires a confirmed diagnosis of AD with evidence of clinically significant agitation, aggression or irritability. Participants are randomly assigned to receive IGC-AD1, an oral liquid formulation, or placebo. Administration is twice daily for 44 days and titration to a full dose requires 2 days.2
The primary endpoint is change in agitation with secondary endpoints identified as sleep disturbances, efficacy of IGC-AD1 on cognition, change in caregiver burden, and, of course, the safety and tolerability of the treatment.2
Beyond AD, more than 30 million Americans suffer from sleep disorders, a risk factor for cognitive decline and cardiovascular disease.3
IGC Pharma is advancing the phase 2 CALMA trial, with further analysis expected by the end of 2025. Additional studies are planned to assess the investigational agent's potential as a disease-modifying therapy for AD.1
