Volume 11, Issue 7S_Part_19 p. P901-P901
Developing Topics
Free Access

P4-302: RVT-101, a 5-ht6 receptor antagonist, as adjunctive therapy with donepezil in adults with mild-to-moderate Alzheimer's disease: Responder analysis

Ilise Lombardo

Corresponding Author

Ilise Lombardo

Axovant Sciences, Inc., New York, NY, USA

Contact e-mail: [email protected]

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Geetha Ramaswamy

Geetha Ramaswamy

Axovant Sciences, Inc., New York, NY, USA

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Stephen C. Piscitelli

Stephen C. Piscitelli

Axovant Sciences, Inc., New York, NY, USA

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Lawrence Friedhoff

Lawrence Friedhoff

Axovant Sciences, Inc., New York, NY, USA

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First published: 01 July 2015
Citations: 1

Background

RVT-101 (formerly known as SB-742457) is an orally administered, potent antagonist of the 5-hydroxytryptamine 6 (5-HT6) serotonin receptor that promotes the release of acetylcholine, glutamate, and other neurotransmitters. Preclinical and clinical data support a complementary mechanism of action with cholinesterase inhibitors. The results of responders on a combined analysis of ADAS-cog, ADCS-ADL, and CDR-SB after 24 weeks of treatment from a Phase 2b trial are presented.

Methods

This was a double-blind, placebo- controlled trial of 684 subjects with mild-to-moderate Alzheimer's disease (MMSE score 10-26) randomized in a 1:1:1 ratio to receive 35 mg RVT-101 (n=236), 15 mg RVT-101 (n=221), or placebo (n=225) as an adjunct to stable donepezil treatment. Safety, tolerability, and efficacy on multiple cognitive and functional endpoints were evaluated at 12, 24, 36, and 48 weeks after initiation of treatment. A logistic regression combined analysis of responders on ADAS-cog, ADCS-ADL, and CDR-SB was performed. Safety and tolerability of RVT-101 at the 24 week primary endpoint is also reported.

Results

In a combined responder analysis of the ADAS-cog, ADCS-ADL, and CDR-SB scales at week 24, subjects who received 35 mg RVT-101 and 15 mg RVT-101 demonstrated a 2.03 (p = 0.032) and 1.89 (p = 0.062) adjusted odds ratio respectively compared to subjects who received donepezil alone at 24 weeks. RVT-101 was well-tolerated by subjects in the study. Drug-related adverse events (AEs) were reported in 6%, 10%, and 9% in the 35 mg, 15 mg, and placebo groups, respectively. AEs leading to withdrawal were similar across treatments (3-5%).

Conclusions

RVT-101 was well-tolerated and effective in improving cognition and function as an adjunct to stable donepezil therapy. These results support the initiation of a Phase 3 confirmatory study evaluating the efficacy of RVT-101 in mild-to-moderate Alzheimer's disease in the second half of 2015.