AChEI Inhibitor Benzgalantamine (Zunveyl) Commercially Launched for Mild to Moderate Alzheimer Disease

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Alpha Cognition has officially launched its new treatment for mild to moderate Alzheimer disease, with a focus on expanding patient access in the long-term care market.

Lauren D’Angelo, MBA

(Credit: Alpha Cognition)

According to a recent announcement, Alpha Cognition has officially launched benzgalantamine (Zunveyl), a recently approved treatment for mild to moderate Alzheimer disease (AD), now available nationwide by prescription in 3 dosage options (5 mg, 10 mg, and 15 mg). To ensure widespread availability and patient support, the company aims to work closely with healthcare providers, payers, and caregivers to enhance education and streamline access.¹

"The launch of Zunveyl is a game-changer in our fight against Alzheimer disease," Lauren D’Angelo, MBA, chief operating officer and chief commercial officer at Alpha Cognition, said in a statement.¹ "Our team has worked relentlessly to bring this treatment to market—from building out an industry-leading infrastructure to hiring a top notch sales team—all in record time. I’m incredibly proud of the dedication and expertise of our team, and we are excited to partner with healthcare professionals to ensure that patients receive the care they deserve."

In July 2024, the FDA approved benzgalantamine, formally known as ALPHA-1062, a prodrug of an approved acetylcholinesterase inhibitor (AChEI) galantamine, for patients with mild-to-moderate AD. ALPHA-1062, a delayed-release oral tablet formulation, is considered a new-generation AChEI inhibitor, with expected minimal gastrointestinal adverse events (AEs).²

The approval was based on results from 4 studies demonstrating the bioequivalence of benzgalantamine to galantamine and galantamine extended-release (ER). Across those studies, only 2% of treated patients had AEs from treatment, with no cases of insomnia observed.³

Benzgalantamine is absorbed in the small intestine as an insert drug. Binding with AChE in the gastrointestinal nervous system is blocked by the addition of a benzyl ester to galantamine. This reduces overstimulation of local neurons, reduces gastrointestinal AEs, and increases bioavailability. Once absorbed, benzgalantamine is metabolized in the liver to the active drug and galantamine is carried to the brain in the circulatory system. The hope is that the improved safety profile of benzgalantamine may help to optimize the effectiveness of treatment by enabling patients to start treatment and stay on therapy longer.

For years, AChE inhibitors were the only specific pharmacologic treatments approved for AD dementia until the recent class of antiamyloids. Although their benefit has shown to be modest, a significant body of evidence supports their effectiveness for improving cognition and their cost-effectiveness. Data from a 2021 published study using over 16,000 patients from the Swedish Dementia Registry showed that ChEI use was associated with higher Mini-Mental State Exam (MMSE) scores at each visit (0.13 MMSE points per year; 95% CI, 0.06-0.20).⁴

Additional data from the analysis showed that ChEI users had a 27% lower risk of death (OR, 0.73; 95% CI, 0.69-0.77) compared with nonusers. Benzgalantamine was associated with lower risk of death (0.71, 95% CI 0.65–0.76) and lower risk of severe dementia (0.69, 95% CI 0.47–1.00) and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points per year, 95% CI 0.07–0.28). Notably, benzgalantamine was the only ChEI demonstrating a significant reduction in the risk of developing severe dementia.

In August 2022, Alpha Cognition announced positive results from one of its bioequivalence studies of benzgalantamine, comprising 40 adult healthy volunteers. Patients were assigned 1:1 to either ALPHA-1062 5 mg twice daily or galantamine hydrobromide 8-mg ER capsules once daily, for 7 days. After a 1-week washout period, patients were then crossed over to the other treatment arm and dosed for 7 days. In addition to demonstrating bioequivalence, the therapy achieved an area under the curve and peak exposures of approximately 107% and 127%, respectively, compared with those generated by galantamine hydrobromide ER.⁵

All told, C_max results for benzgalantamine were bracketed between the hydrobromide IR and ER formulation (lower than IR, higher than ER) providing a robust and enhanced data set for the NDA filing. According to the company at the time of the release, the data further described the delayed release profile of benzgalantamine and added to the NDA data set by characterizing the therapeutic and acceptable exposures compared to both the immediate-release and extended-release products.

REFERENCES
1. Alpha Cognition Announces the Commercial Launch of ZUNVEYL (Benzgalantamine) for the Treatment of Mild to Moderate Alzheimer’s Disease. News Release. Alpha Cognition. Published March 18, 2025. Accessed March 18, 2025. https://www.businesswire.com/news/home/20250319665873/en/Alpha-Cognition-Announces-the-Commercial-Launch-of-ZUNVEYL-Benzgalantamine-for-the-Treatment-of-Mild-to-Moderate-Alzheimers-Disease
2. Alpha Cognition’s Oral Therapy ZUNVEYL® Receives FDA Approval to Treat Alzheimer's Disease. News Release. Alpha Cognition. Published July 29, 2024. Accessed March 18, 2025. https://www.alphacognition.com/investors/news/alpha-cognitions-oral-therapy-zunveyl-receives-fda-approval-to-treat-alzheimers-disease-
3. Alpha Cognition Announces FDA Acceptance of New Drug Application for ALPHA-1062 for Mild-to-Moderate Alzheimer’s Disease. Alpha Cognition. December 7, 2023. Accessed March 18, 2025. https://www.alphacognition.com/investors/news/alpha-cognition-announces-fda-acceptance-of-new-drug-application-for-alpha-1062-for-mild-to-moderate-alzheimers-disease
4. Xu H, Garcia-Ptacek S, Jonsson L, et al. Long-term effects of cholinesterase inhibitors on cognitive decline and mortality. Neurology. 2021;96(17):2220-2230. doi.10.1212/WNL 0000000000011832
5. Alpha Cognition Announces Positive Topline Results from Bioequivalence Study with ALPHA-1062 in Development for Alzheimer’s Disease. News release. Alpha Cognition. August 22, 2024. Accessed March 18, 2025. https://www.alphacognition.com/investors/news/alpha-cognition-announces-positive-topline-results-from-bioequivalence-study-with-alpha-1062-in-development-for-alzheimers-disease