Ultra long‐acting oral therapies for Alzheimer's: Proof of principle

Abstract Background Poor compliance [1] and high rates of discontinuation [2] with daily oral therapy, such as memantine hydrochloride (HCl) and donepezil HCl, in Alzheimer’s patients compromises the effectiveness of medications that may slow progression of disease severity. Lyndra Therapeutics is developing extended release (ER) capsules for long‐acting oral therapies in several therapeutic areas, including Alzheimer’s disease. Weekly administered oral therapies may improve adherence, provide more consistent plasma drug levels, and facilitate observed administration. Method The Lyndra ER capsule has modular features serving specific functions for extended delivery to the stomach. The features include a star‐shaped drug‐releasing formulation (stellate) with up to six drug‐loaded polymer arms formulated to achieve controlled drug release while maintaining gastric residence. Polymer‐coated arms yield a steady rate of drug release into the stomach. The formulation is designed to lose its structural integrity after a period of residence and to pass safely through the GI tract. To test the feasibility of this approach, 8 healthy volunteers received a single dose of LYN‐157 containing 40 mg of memantine HCl and 38mg of donepezil HCl while under observation in a Phase 1 unit for 7 days. Results Plasma drug concentrations peaked within 48‐72 hours. LYN‐157 achieved consistent and linear release of both memantine and donepezil, with concentrations maintained over 7 days. No serious adverse events were observed. The most common adverse events were headache, abdominal pain and nausea, generally beginning near time of administration and resolving within 2 days. Conclusion Lyndra's novel drug delivery technology achieved controlled release of memantine and donepezil resulting in consistent pharmacokinetics (PK) exposure over 7 days. The ability to deliver one or more oral drugs over one week with a single oral capsule has the potential to improve compliance, quality of life, and care of people with Alzheimer's disease. References: 1. Austrom MG, Boustani M, LaMantia MA. Ongoing Medical Management to Maximize Health and Well‐being for Persons Living With Dementia. Gerontologist. 582018. p. S48‐57. 2. Haider B, Schmidt R, Schweiger C, Forstner T, Labek A, Lampl C. Medication adherence in patients with dementia: an Austrian cohort study. Alzheimer Dis Assoc Disord. 2014;28(2):128‐33.