Interim Phase 2 Data Highlight IGC-AD1 as a Potential Therapy for Alzheimer Disease Agitation

Author(s):

Over a 6-week period, patients taking IGC-AD1, on average, experienced a more significant reduction in agitation scores compared with those on placebo, with effects seen as early as week 2.

Ram Mukunda

Newly announced interim data from a phase 2 trial showed that treatment with IGC-AD1 (IGC Pharma), an investigational agent, resulted in clinical and statistically significant reduction in agitation among patients with Alzheimer disease (AD) in comparison with placebo. Although the analysis included a small portion of patients, the effects were more pronounced than that observed with previously approved medications, and highlight the potential of a tetrahydrocannabinol (THC)-based candidate to treat symptoms of AD.

The phase 2 trial featured 146 patients, with interim results based on a group of 26 participants. After 6 weeks of treatment, the least square (LS) mean difference in Cohen Mansfield Agitation Inventory (CMAI) score, the primary end point, between the active and placebo groups was –10.45 (95% CI, –20.20 to –0.72). At weeks 2 and 6, the interim Cohen’s d effect size was 0.79 and 0.66, respectively, with a P value of 0.037 for weeks 2 and 6 combined.

"We are excited with the positive interim results from the Phase 2 trial of IGC-AD1 for agitation in dementia due to Alzheimer's disease. IGC-AD1’s interim results demonstrate a clinical and statistically significant reduction in agitation compared to placebo, suggesting a strong plausibility to address a substantial unmet medical need," Ram Mukunda, chief executive officer of IGC Pharma, said in a statement. "This interim data validates IGC-AD1's potential as a transformative therapeutic option with a large market opportunity in Alzheimer's disease management. We are actively pursuing next steps, including with regulators, and remain committed to advancing IGC-AD1 toward commercialization."

The phase 2, multi-site, randomized, double-blind, placebo-controlled trial is ongoing and continues to enroll. In the study, patients who were randomly assigned to IGC-AD1 received the oral liquid formulation twice daily for 6 weeks, with no placebo run-in, and titration to full dose over 2 days. Those included in the trial had clinically significant agitation, which was defined by Neuropsychiatric Inventory scores greater than 4, a diagnosis based on the IPA definition, and agitation that was not attributable to another psychiatric disorder, suboptimal care conditions, or other underling medical condition.

IGC-AD1’s effect of the primary end point of CMAI also seemed to outperform brexpiprazole (Rexulti; Otsuka/Lundbeck), the first approved medication specific for AD agitation. In the 2 phase 3 studies that brexpiprazole was approved on (NCT03548584; NCT1862640), the atypical antipsychotic demonstrated LS treatment differences of –5.32 (95% CI, –8.77 to –1.87) and –3.77 (95% CI, –7.38 to –0.17), respectively, in comparison with placebo over a 12-week span. A post-hoc subgroup analysis of the latter trial (NCT01922258) revealed LS mean treatment differences of –5.06 (95% CI, –8.99 to –1.13). Although these studies were 12 weeks in length, the data appear to favor IGC-AD1.

Mukunda added, "We foresee a medication that can help alleviate caregiver burden and family distress as managing Alzheimer’s patients, especially ones with agitation, can have a significant emotional toll on families. With IGC-AD1's promising clinical profile, we are confident in its ability, subject to further trials, to improve patient outcomes and drive shareholder value."¹

IGC-AD1’s formulation combines a CB1 receptor partial agonist with anti-neuroinflammatory properties that help balance neurotransmitter imbalance and an inflammasome inhibitor that targets the upregulation of inflammasome-3. In 2021, prior to the start of the phase 2 trial, a successful phase 1 study assessed the safety and tolerability of the therapy. The double-blind trial, which featured participants with mild to severe AD who received 3 doses of the agent, showed that ICG-AD1 is safe and tolerable. On anxiety and depression scales, investigators documented a decrease of approximately 50% to 60% in patients who received the drug. For agitation, treated patients showed a decrease of approximately 35% to 60%.³

REFERENCES
1. IGC Pharma announces positive interim results for IGC-AD1 in reducing Alzheimer’s agitation. News release. IGC Pharma. March 20, 2024. Accessed March 20, 2024. https://www.businesswire.com/news/home/20240320069009/en/IGC-Pharma-Announces-Positive-Interim-Results-for-IGC-AD1-in-Reducing-Alzheimer%E2%80%99s-Agitation
2. The promise of IGC-AD1. IGC Pharma. https://igcpharma.com/igc-ad1/. Accessed March 20, 2024.
3. Phase 1 clinical trial data indicate IGC’s THC-based investigational new drug may reduce symptoms of dementia in Alzheimer’s patients. News release. IGC Pharma. December 2, 2021. Accessed March 20, 2024. https://www.businesswire.com/news/home/20211202005635/en/Phase-1-Clinical-Trial-Data-Indicate-IGC%E2%80%99s-THC-based-Investigational-New-Drug-May-Reduce-Symptoms-of-Dementia-in-Alzheimer%E2%80%99s-Patients