RVT-101 as an adjunctive therapy to Donepezil in patients with mild-to-moderate Alzheimer's disease: benefits in cognition and function through 48 weeks
New results from a 684-subject phase 2b clinical trial evaluating RVT-101, as an adjunctive therapy to Donepezil in patients with mild-to-moderate Alzheimer's disease, were presented at the 2015 Alzheimer's Association International Conference ( AAIC ) in Washington, D.C.
In the analysis of all patients with complete data at each study visit, patients receiving 35 mg RVT-101 in combination with Donepezil have 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.
Completer 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.
On a third endpoint measured, the Clinical Dementia Rating – Sum of Boxes ( CDR-SB ), the 35mg RVT-101 treatment group demonstrated numerical improvements over the control group which were statistically significant at week 12, but not at other time points.
The CDR-SB has not been used to obtain the approval of any currently marketed Alzheimer's disease treatment.
No drug-related serious adverse events were observed in the RVT-101 treatment groups at 24 or 48 weeks. There was no statistically significant difference in withdrawals and adverse events between the treatment groups and control group, with a slightly lower percentage of withdrawals and drug-related adverse events, including falls, in the 35mg treatment group than in the control group.
The completer analysis has reinforced the results of the previously published ITT analysis. ITT analyses use estimated values for patients who had incomplete data.
The results of the ITT analysis showed the 35mg treatment group had statistically significant improvements relative to placebo of ADAS-cog at 12, 24, and 48 weeks and ADCS-ADL at 12, 24, and 36 weeks.
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.
RVT-101 has been studied in 13 clinical trials and dosed in over 1,250 human subjects with a favorable safety and tolerability profile. ( Xagena )
Source: Axovant, 2015