G2GBio: "Positive Signal for Development of Monthly Donepezil (GB-5001) Formulation" 

Life science company G2GBio has announced positive results from a low-dose clinical trial of their long-acting Alzheimer's treatment, "Monthly Donepezil (GB-5001)." The study showed that the drug maintained a stable blood concentration for over a month without considerable(or significant)

G2GBio plans to present these clinical trial results at the Alzheimer's Association International Conference (AAIC) in Amsterdam, the Netherlands, scheduled for July. The company explained that the ongoing Phase 1 clinical trial of Donepezil in Canada involved administering microspheres containing Donepezil via intramuscular injection to 48 healthy male participants. Currently, the safety, pharmacokinetics, and drug release profiles for the cohort of low-dose group were observed for 64 days. The results indicated that the drug maintained a consistent blood concentration above a certain threshold for more than a month, with no observed adverse reactions.

G2GBio also mentioned that recently obtained mid-dose pharmacokinetic results demonstrated a dose-dependent release profile similar to expectations. They further stated that they are currently conducting follow-up observations after administering the final high-dose to all participants in March. Once the high-dose results are obtained, they will be able to determine the dosage of GB-5001 that achieves bioequivalence with the RLD, Aricept 10mg oral formulation, through repeated dosing predictions and statistical analysis. This will also help in estimating the number of participants needed for future studies.

In addition to presenting these clinical trial results at AAIC, G2GBio plans to announce the study results of newly developed formulation on an alternate route of administration, moving from intramuscular to subcutaneous injection, making the administration of the Alzheimer's treatment more convenient. The company's CEO, Hee-Yong Lee, expressed confidence in meeting the expected results and securing reproducibility in manufacturing at a commercial scale. He also emphasized that this would accelerate global licensing out and open up opportunities for exporting their platform technology, including diabetes and obesity treatments.

Donepezil is one of the most commonly prescribed ingredients in Alzheimer's treatment. The current daily oral formulations have drawbacks such as difficulties in swallowing for dementia patients or reduced adherence due to cognitive decline. However, G2GBio's modified formulation of Donepezil, GB-5001, administered through a once-a-month injection, has been evaluated to improve medication adherence by maintaining a stable therapeutic effect.

Furthermore, G2GBio has completed the development of a 1-month sustained-release subcutaneous injection formulation (for self-administration) of Donepezil, and last month, they submitted an Investigational New Drug (IND) application to the Korean Ministry of Food and Drug Safety for both subcutaneous and intramuscular injection formulations. Overcoming the injection site reaction associated with extended-release injectables by lowering the microsphere amounts in the body by increasing the drug loading is crucial.

G2GBio explained that they used two improved microsphere formulations with significantly increased drug content for the upcoming clinical trial. Despite the substantial increase in drug dosage, they achieved a state of managed initial drug release below a certain threshold, allowing the drug to persist for over a month while significantly reducing injection site reactions.