Medical staff and patients are moving through Seobuk Hospital in Eunpyeong-gu, Seoul, which was designated on April 4, 2024, as the city’s first hospital dedicated to treating patients with severe dementia 2024.4.4 / News1

The competition to develop long-acting injectable (LAI) formulations of donepezil, an Alzheimer's treatment, is heating up. These new drugs aim to address the adherence challenges associated with the current standard oral medication.

While oral donepezil has proven effective in improving cognitive function in Alzheimer's patients, its daily dosing requirement presents real-world treatment obstacles. In response, Inventage Lab and G2G Bio are pioneering monthly injectable alternatives.

Industry sources report that donepezil works by inhibiting acetylcholinesterase (AChE), thereby enhancing cognitive function. Previous studies show that a daily 10 mg oral dose achieves an average blood concentration of 50.6 ng/mL, corresponding to a 74.7% AChE inhibition rate (Emax).

Research indicates that maintaining an AChE inhibition rate above 65% strongly correlates with cognitive improvement.

However, patients with cognitive decline often struggle with self-administration, necessitating constant caregiver supervision. This has led to ongoing concerns about treatment adherence and efficacy fluctuations during long-term therapy.

Monthly LAIs offer a promising solution by maintaining consistent blood concentrations while reducing dosing frequency. This approach could minimize efficacy variations and ease the burden on both patients and caregivers.

A researcher at Inventage Lab is conducting drug development research / Provided by Inventage Lab

Comparing Phase I Clinical Results of Two LAI Candidates

Inventage Lab's IVL3003 and G2G Bio's GB-5001A are currently under development. Recent Phase I trial results have revealed distinct pharmacokinetic (PK) and pharmacodynamic (PD) profiles between these two candidates.

Both studies evaluated healthy adults after a single intramuscular injection, allowing for direct comparison under similar conditions.

IVL3003 demonstrated over twice the drug exposure (AUC) of GB-5001A at a 15% lower dose, reaching therapeutic concentrations with a single administration.

IVL3003 achieved peak concentration (Tmax) around two weeks post-injection, maintaining stable blood levels. Notably, it sustained significant concentrations beyond four weeks, supporting its potential as a long-acting formulation.

The maximum AChE inhibition rate for IVL3003 reached approximately 85%, matching or exceeding the efficacy of standard oral donepezil regimens.

In contrast, GB-5001A fell short of therapeutic standards for both blood concentration and efficacy markers in single-dose trials. Even at the highest dose, it failed to achieve clinically effective concentrations, with AChE inhibition rates only reaching the 30% range.

However, GB-5001A showed delayed drug release, with Tmax extending beyond four weeks. Some subjects exhibited a dual-peak concentration pattern.

G2G Bio attributes these characteristics to flip-flop pharmacokinetics, suggesting that repeated dosing could lead to gradual drug accumulation, potentially reaching blood concentrations similar to oral medications.

On April 4, 2024, medical staff at Seobuk Hospital in Eunpyeong-gu, Seoul—designated as the city’s first hospital dedicated to severe dementia patients—are conducting a music therapy program with patients ahead of the opening ceremony 2024.4.4 / News1

Domestic Firms Build Clinical Evidence for Novel Treatment Options

Industry experts emphasize that for long-acting drug development, demonstrating clinical efficacy through AChE inhibition is crucial. Achieving sufficient drug exposure at lower doses, while maintaining safety, will be key to competitive advantage.

Both candidates are still in Phase I trials with healthy volunteers. Future studies must address efficacy and safety in Alzheimer's patients, as well as long-term dosing effects and potential side effects.

G2G Bio is collaborating with Humedix and Korea Pharma, while Inventage Lab has partnered with Chong Kun Dang. These collaborations may accelerate commercialization efforts and development strategies.

Researchers must also establish the correlation between sustained blood concentrations and clinical cognitive improvements with repeated dosing.

An industry insider commented that long-acting injectables that maintain therapeutic effects with monthly dosing, eliminating daily medication hassles, are a game-changer for patients and caregivers alike. The clinical evidence being gathered by these domestic companies could soon translate into groundbreaking treatment options for Alzheimer's patients.

The competition to develop long-acting injectable (LAI) formulations of donepezil, an Alzh …

Alzheimer's Breakthrough: Monthly Injections of IVL3003 vs. GB-5001A—Which is More Effective?