Exploring GB-5001 Long-acting Injectable Donepezil: A New Frontier in Dementia Treatment

GB-5001, a long‑acting injectable formulation of donepezil, produces extended systemic exposure and—if confirmed in patient trials—could materially improve adherence in dementia care.

A Phase 1, open‑label, active‑controlled dose‑escalation study enrolled 50 healthy male volunteers to assess GB-5001’s pharmacokinetics and safety across 70 mg, 140 mg and 280 mg intramuscular or subcutaneous doses. The healthy, all‑male cohort limits generalizability to older, mixed‑sex patients with Alzheimer’s disease and highlights the need for subsequent trials that are age‑ and sex‑diverse.

GB-5001 produced a 3–4‑fold longer half‑life and sustained acetylcholinesterase inhibition versus oral donepezil, as reported in the GB-5001 pharmacokinetics. Dose‑proportional increases in AUC and simulations of four monthly doses predicted near‑steady plasma concentrations with a modest peak‑to‑trough swing; pharmacodynamic assessments documented persistent AChE inhibition through the dosing interval. Those findings support a realistic shift toward once‑monthly administration if efficacy and tolerability are replicated in patients.

The safety profile was favorable: no serious adverse events occurred and most adverse events were mild, localized to the injection site, or transient laboratory abnormalities. The trial’s safety profile summary noted common injection‑site pain or induration and a single reversible Grade‑3 creatine phosphokinase elevation, without clinically meaningful systemic signals or treatment withdrawals. Most events resolved without intervention, supporting outpatient administration with routine monitoring.

CYP2D6 phenotype materially affected GB-5001 exposure, with apparent differences in concentration‑time profiles across metabolizer groups consistent with known donepezil metabolism. The genotype‑stratified sample was small and preliminary, but directionality aligns with expected CYP2D6 effects. Prospective genotype stratification or phenotype‑guided dose considerations should be built into later-phase trials to refine dosing and safety monitoring.