Date: 2015-07-22
Type of information: Presentation of results at a congress
phase: 2b
Announcement: presentation of results at the Alzheimer's Association International Conference 2015 (AAIC) in Washington
Company: Axovant Sciences (Bermuda - USA - NY)
Product: RVT-101
Action
mechanism: 5-HT6-receptor antagonist. RVT-101 is an orally administered, potent antagonist of the 5-HT6 serotonin receptor. Antagonism of the 5-HT6 receptor is a novel mechanism of action that promotes the release of acetylcholine, glutamate and other neurotransmitters thought to improve cognition and function in patients suffering from Alzheimer\'s disease and other forms of dementia. Preclinical and clinical data support a complementary mechanism of action with cholinesterase inhibitors. RVT-101 has been studied in 13 clinical trials involving over 1,250 human subjects with a favorable safety and tolerability profile. Axovant intends to commence a confirmatory phase 3 clinical study testing RVT-101 on a background of donepezil therapy in mild-to-moderate Alzheimer\'s disease patients in the fourth quarter of 2015.
Disease: Alzheimer's disease
Therapeutic area: Neurodegenerative diseases
Country:
Trial details:
Latest
news: * On July 22, 2015, Axovant Sciences announced new results from a 684-subject phase 2b clinical trial evaluating Axovant's lead product candidate, RVT-101, as an adjunctive therapy to donepezil in patients with mild-to-moderate Alzheimer's disease. Axovant presented these results at the 2015 Alzheimer's Association International Conference (AAIC) in Washington, D.C.In Axovant's analysis of all patients with complete data at each study visit, patients receiving 35 mg RVT-101 in combination with donepezil demonstrated statistically significant improvements in cognition and function at 12, 24, 36, and 48 weeks as compared to patients receiving donepezil alone. Cognition was measured by the Alzheimer's Disease Assessment Scale – cognitive subscale (ADAS-cog) and function was measured by the Alzheimer's Disease Cooperative Study – Activities of Daily Living scale (ADCS-ADL). ADAS-cog and ADCS-ADL have each been used as endpoints to obtain regulatory approval of currently-marketed Alzheimer's disease treatments. Axovant's complete analysis reinforces the protocol-specified analysis of the intent-to-treat (ITT) population from this same study, published in Alzheimer's & Dementia, where patients receiving 35 mg RVT-101 plus donepezil also demonstrated statistically significant improvements on the ADAS-cog and ADCS-ADL compared to patients receiving donepezil alone. These results also suggested a consistent dose response across placebo, 15mg RVT-101, and 35mg RVT-101, the only doses that were tested. In this study, 684 subjects with mild to moderate Alzheimer’s disease were randomized to receive 35 mg RVT-101, 15 mg RVT-101, or placebo as an adjunct to stable donepezil treatment. The study included a 24-week double-blind randomized phase and an optional, additional 24-week blinded extension. An analysis of covariance (ANCOVA) method was used to evaluate multiple endpoints on cognition and function based on observed data, including the ADAS-cog, CDR-SB, and ADCS-ADL at weeks 12, 24, 36, and 48. The proportion of subjects completing the study ranged from 86-89% from week 0 to week 24 and from 87-89% from week 24 to week 48. On ADAS-cog and ADCS-ADL respectively, subjects who received 35 mg RVT-101 achieved a 1.29 (p = 0.008) and 1.72 (p = 0.016) point benefit at week 12; a 1.63 (p = 0.007) and 2.11 (p = 0.016) point benefit at week 24; and a 1.82 (p = 0.018) and 2.34 (p = 0.048) point benefit at week 48, all compared to donepezil alone. Subjects who received 35 mg RVT-101 achieved a statistically significant benefit on CDR-SB compared to subjects who received donepezil alone only at 12 weeks after initiation of treatment. Mean ADAS-cog, ADCS-ADL and CDR-SB values for the 15-mg group were generally numerically superior to placebo but the differences were not statistically significant. In this analysis of subjects completing a Phase 2b study in subjects with mild-to-moderate Alzheimer’s disease, the 35 mg dose of RVT-101 was shown to be effective in improving cognition and function as an adjunct to stable donepezil at multiple time points. Given the low drop-out rate, this analysis provides an accurate representation of the study. The 35 mg dose of RVT-101 will be advanced into a Phase 3 study. Axovant intends to commence a confirmatory phase 3 program in the fourth quarter of 2015. * On June 29, 2015, Axovant Sciences, a clinical-stage biopharmaceutical company focused on the treatment of dementia, announced the acceptance of two presentations at the Alzheimer\'s Association International Conference 2015 (AAIC) being held in Washington, D.C. from July 18-23, 2015. The data will be presented via oral and poster presentations as follows: Efficacy of RVT-101 in Mild-Moderate Alzheimer\'s Disease: Completer Analysis (Oral Presentation): The Efficacy of RVT-101, a 5-HT6 Receptor Antagonist, As an Adjunct to Donepezil in Adults with Mild-to-Moderate Alzheimer\'s Disease: Completer Analysis of a Phase 2b Study will be presented during the Developing Topics Session: Clinical Trial Results on Wednesday, July 22, 2015, 2:00-3:30 p.m. (Hall E; # DT-01-04). Efficacy of RVT-101 in Mild-Moderate Alzheimer\'s Disease: Responder Analysis (Poster Presentation): RVT-101, a 5-HT6 Receptor Antagonist, As Adjunctive Therapy with Donepezil in Adults with Mild-to-Moderate Alzheimer\'s Disease: Responder Analysis will be presented during the Therapeutics: Clinical poster session on Wednesday July 22, 2015, 9:30 a.m. - 4:15 p.m. (Exhibit Hall E; # P4-302).
