Neurodyn Inc. announced today that its’ Alzheimer’s prescription drug candidate – Memogain® has completed the initial Part I of a Phase IA clinical trial in December 2013 at the Centre for Human Drug Research (CHDR) in Leiden, Netherlands – the leading European centre for the conduct of Alzheimer’s clinical trials. The following is a summary of the initial Part I of the Memogain®Phase IA Single Ascending Dose Clinical Trial conducted in December 2013:
Location: The Centre for Human Drug Research [CHDR] Leiden Netherlands, the leading European center for the conduct of Alzheimer’s clinical trials.
Caution: This is an interim report of results in a small group of healthy young adults that were given two doses of Memogain via the intranasal route.
Problem: Side Effects – Galantamine has been known for thousands of years to be a cognitive enhancer, its main and significant draw-back is its gastrointestinal side effects which limits the dose that could be given and reduces patient compliance.
Solution: Pro-drug – Memogain is a pro-drug of Galantamine which has been designed to significantly increase the delivery of galantamine to the brain with the following benefits;
- Increased effectiveness as cognition enhancer,
- Absence of gastrointestinal side effects,
- No requirement for up-titration, and
- Disease-modifying activity.
Mechanisms of Action – Subsequent to the initial introduction of Galatamine in the mid 90′s, Neurodyn’s scientific team confirmed that Galantamine’s principal mechanism of action was to sensitize acetylcholine receptors to their neurotransmitter acetylcholine. Galantamine also exhibits modest acetylcholinesterase inhibitor activity. These two mechanisms work together to improve cognitive function.
The Memogain Phase IA clinical study is divided in two distinct parts:
Part I -a double-blind, placebo-controlled study in healthy young subjects – two single ascending doses of Memogain (5.5mg and 11 mg); sample size n=16.
Part II - a reference controlled study in healthy elderly subjects (aged 66 and over) – three single ascending doses of Memogain (22mg, 33mg, 3rd dose to be determined), reference-controlled (16 mg oral galantamine, 10mg oral donepezil), sample size n=42.
Total sample size of Phase IA study: n=58.
Part I has been completed – Summary Report;
Safety: The safety data is flawless, in particular when considered that there may be much higher galantamine levels in the brain (delivered via Memogain as a pro-drug), than if galantamine (the active drug) were administered orally. There was no hint of any central or significant peripheral adverse effects. In contrast, at the higher dose of Memogain (11 mg) the equivalent dose of oral galantamine would be expected to have caused severe gastrointestinal side effects in up to 30% of subjects. A
transient prickling or burning sensation in the nose was reported by several subjects, however this irritation was considered mild and typical for a nasal spray formulation. Given this excellent Memogain safety and tolerability profile, CHDR has recommended to immediately proceed without any change in protocol to part II of the clinical study.
Cognition: CHDR was particularly impressed by the cognition data obtained for the higher dose cohort (11 mg Memogain ≡ 8 mg of galantamine). The Study Director Geert Jan Groeneveld, MD, particularly stressed the results of some of the ‘working memory’ tests, explaining that CHDR has not seen any sign of cognition enhancement in their earlier study in healthy young volunteers of 8mg oral galantamine, or their separate study of 10 mg of donepezil (Aricept). The surprising enhancement in working memory seen with Memogain in young healthy volunteers underscores the potential for this drug candidate to benefit elderly with impaired memory and Alzheimer’s disease patients.
Summary: The Interim Data Report from CHDR confirms for the two doses of intranasal Memogain tested that the drug is effectively absorbed is well tolerated and did not cause any of the side effects observed for a comparable dose of galantamine (8mg) or for the daily recommended dose of donepezil (10mg), the market leader in the field. In addition, by applying a combination of working memory tests (CHDR’s “NeuroCart”), convincing evidence was established for cognitive enhancement even in healthy young volunteers.
The Part I results underscore the potential of Memogain to provide medical benefit not only to Alzheimer patients but also to otherwise healthy elderly with impairments in memory, so called MCI patients. This is in clear contrast to the experience with existing treatments that do not improve cognition or function among elderly with mild cognitive impairment and were associated with a greater risk of significant gastrointestinal side effects (Tricco et al., 2013).
Part II of the study will evaluate the response of elderly healthy subjects to Memogain. This group is expected to exhibit some age-related cognitive impairment and is likely to be more sensitive to the typical side effects of galantamine and donepezil (nausea, diarrhea, vomiting).
Part II is intended to show that also at higher doses Memogain will NOT cause any of the typical side effects of the presently available Alzheimer drugs and, moreover, will produce significantly higher and longer lasting cognitive enhancement than current Alzheimer’s treatments.
Regulatory – Path
As a pro-drug of an already approved AD drug with a much improved safety profile, Memogain should qualify for a more rapid and less costly path to market authorization by the US FDA.
For further information please contact;
Neurodyn Life Science Inc.