Drug Development.

Area of Science:

• Pharmacology
• Neuroscience
• Drug Development

Background:

• ZUNVEYL (benzgalantamine) is a novel, pharmacologically inactive prodrug of galantamine, approved in 2024 for mild to moderate Alzheimer's dementia.
• It utilizes the 505(b)(2) regulatory pathway, leveraging FDA's prior findings for galantamine hydrobromide (Razadyne®).
• ZUNVEYL's delayed-release formulation aims to mitigate gastrointestinal side effects common with acetylcholinesterase inhibitors.

Purpose of the Study:

• To assess the relative bioavailability of ZUNVEYL delayed-release (DR) tablets compared to galantamine hydrobromide immediate-release (IR) tablets.
• To evaluate these comparisons under both fed and fasting conditions in healthy adult subjects.

Main Methods:

• Two open-label, randomized, crossover studies (N=34 each) were conducted: one under fed conditions (ALPHA-1062-01) and one under fasting conditions (ALPHA-1062-02).
• Subjects received single doses of ZUNVEYL DR 5 mg or galantamine hydrobromide IR 4 mg.
• Study protocols adhered to Good Clinical Practice (GCP) standards and underwent ethics review.

Main Results:

• ZUNVEYL, the prodrug, was minimally detected in plasma (approx. 1%), suggesting a potentially wider safety margin.
• Pharmacokinetic analysis indicated that ZUNVEYL was bioequivalent to galantamine hydrobromide IR for key parameters (AUC0-t, AUC0-∞) under both fed and fasting conditions.
• Bioequivalence for Cmax was demonstrated under fed conditions.

Conclusions:

• ZUNVEYL was well-tolerated with no serious adverse events reported.
• The bioequivalence findings establish a scientific basis for ZUNVEYL's approval, linking its efficacy and safety to established galantamine products.
• ZUNVEYL presents a promising therapeutic option for Alzheimer's dementia, potentially improving patient compliance due to reduced GI adverse effects.