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

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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, chief executive officer of IGC Pharma

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."

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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
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