(NYSE American: IGC), India Globalization Capital, Inc. (IGC) today announces preliminary results for its exploratory endpoints from its Phase 1 IGC-AD1 clinical trial. IGC-AD1 is a proprietary cannabis-based investigational new drug candidate for patients suffering from Alzheimer’s disease. The Phase 1 clinical trial provided valuable insights on Pharmacokinetics (PK) and genotyping that will be essential in determining optimal dosing moving into subsequent trials, subject to U.S. Food and Drug Administration (FDA) approval.
The clinical trial results were submitted in the Clinical/Statistical Report (“CSR”) filed with the FDA on December 1, 2021. In addition, as previously disclosed, data from the secondary endpoints, neuropsychiatric symptoms in Alzheimer’s patients, and other relevant data are available on Form 8-K filed with the SEC on December 2, 2021.
Alzheimer’s disease impacts about 50 million people worldwide, and approximately 66% are women (alz.org). Unfortunately, there is no cure for Alzheimer’s and no FDA-approved pharmaceuticals to treat many of the symptoms, including agitation, in Alzheimer’s.
Pharmacokinetics studies how long it takes for the body to absorb, process, metabolize, and eliminate a drug after being administered. Understanding how long it takes a drug to produce the intended effects and when those effects will diminish can help determine the appropriate and safe frequency of dosing.
Tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, is metabolized by the CYP4502C9 enzyme. This enzyme is also responsible for metabolizing and eliminating many other families of drugs, including S-warfarin, tolbutamide, phenytoin, losartan, diclofenac, and celecoxib. The CYP4502C9 enzyme converts THC to its active metabolite OH-THC.
The trial measured Tmax, the length of time it takes for the substance to reach its maximum concentration in the body, and T1/2, which is the length of time it takes for the concentration to decline to half the Tmax value. These two metrics provide guidance on when the maximum effects of the drug will be felt and when the impact of the drug will start to decline significantly. We measured Tmax and T1/2 for both THC and the metabolized substance OH-THC.
- The mean Tmax was 2.15 hours (range 1.0-3.5) for THC and 1.9 hours (range 1.0-4.0) for OH-THC
- The mean T1/2 was 3.60 hours (range 0.7-12.87) for THC and 3.30 hours (range 1.05-5.7) for OH-THC
These results indicate that dosing two or three times per day may be safe for patients, as the first and potentially second dose would be eliminated from the body before subsequent doses are given.
The CYP2C9 gene encodes the cytochrome CYP2CP enzyme. This gene is highly polymorphic, which means not everyone makes the gene in the same way. Variations in the gene can impact the level of enzyme activity and how quickly the bodily metabolizes substances, including THC. These variations are stratified into groups of metabolizers - poor (PM), intermediate (IM), normal (NM), and ultra-rapid (UM) (Gaedigk A, et al., 2008; Caudle K E, et al., 2017)
We used a blood test to determine that 62% of the study population (N=13) were classified as IM and 38% NM. 100% of study participants were of Hispanic ethnicity. The IM / NM split was consistent with the known distribution of the overall Hispanic population but may not be representative of other populations.
The Tmax values were close for IM and NM participants. However, the T1/2 of THC and OH-THC did vary. This indicates, subject to more trials, that optimal dosing frequency could vary based on a person’s polymorphism of the CYP2CP gene.
- THC: Tmax was 2.38 hours for the NM group and 2.00 hours for the IM group
- OH-THC: Tmax 1.75 hours for the NM and 2.00 hours for the IM group
- THC: T1/2 was 1.73 hours for the NM group and 5.09 hours for the IM group
- OH-THC: T1/2 was 2.98 for the NM group and 3.51 hours for the IM group
We plan to use the results from this study to inform the design of Phase 2 and Phase 3 clinical trials, subject to FDA approval. IGC-AD1 is an investigational new drug that has not been approved as a medication by any regulatory body in any country. Although the Phase 1 trial has been completed, and certain data has been collected, IGC-AD1’s safety, tolerability, and efficacy need to be further established through trials on larger and more diverse groups of Alzheimer’s patients.
India Globalization Capital, Inc. (IGC) engages in the development of cannabinoid-based therapies for healthcare applications. The company currently operates two lines of business: life sciences and infrastructure. The life sciences business recently completed a Phase 1 clinical trial on Alzheimer’s patients using a THC-based investigational new drug. The second line of business is an infrastructure business based in India. IGC is headquartered in Potomac, MD.
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934. These forward-looking statements are based largely on IGC’s expectations and are subject to several risks and uncertainties, certain of which are beyond IGC’s control. Actual results could differ materially from these forward-looking statements as a result of, among other factors, the Company’s failure or inability to commercialize one or more of the Company’s products or technologies, including the investigational new drug or formulation described in this release, or failure to obtain FDA approval for the investigational new drug or additional clinical trials; testing results from human clinical trials that may not be favorable or as anticipated or consistent with the results obtained from Phase 1 trials; general economic conditions that are less favorable than expected, including as a result of the ongoing COVID-19 pandemic; the FDA’s general position regarding cannabis- and hemp-based products; and other factors, many of which are discussed in IGC’s SEC filings. IGC incorporates by reference the human trial disclosures and Risk Factors identified in its Annual Reports on Form 10-K filed with the SEC on June 14, 2021, and Quarterly Report on Form 10-Q, filed with the SEC on August 11, 2021, and October 29, 2021 as if fully incorporated and restated herein. In light of these risks and uncertainties, there can be no assurance that the forward-looking information contained in this release will occur.