Investigational Neurotransmitter May Enhance Treatment for Alzheimer’s Symptoms

WASHINGTON — Alzheimer’s disease is the most common cause of cognitive dysfunction in the elderly and contributes to the significant burden affecting the current healthcare environment. Although currently no agents exist that can prevent the progression of the disease, a number of treatments are effective at mitigating the symptoms of the condition.

Promising cognitive-enhancing agents are being investigated in combination with these existing therapies to address the symptomatic cognitive and functional impairment associated with this devastating progressive illness.

Investigators reported on the results of a 48-week phase 2b placebo-controlled trial conducted to assess the efficacy of RVT-101, a 5-hydroxytryptamine 6 (5-HT6) receptor antagonist, as symptomatic therapy when co-administered with donepezil in patients with Alzheimer’s disease. The data were presented by Lawrence T. Friedhoff, MD, PhD, Chief Development Officer of Axovant Sciences, Inc., at the 2015 Alzheimer’s Association International Conference.

RVT-101 is believed to promote the release of neurotransmitters that are associated with memory, cognition, and function.

The study comprised 684 patients with mild to moderate Alzheimer’s disease who were randomly assigned to receive 35 mg RVT-101, 15 mg RVT-101, or placebo as add-on treatment to donepezil. Cognitive performance was assessed using the Alzheimer’s Disease Assessment Scale (ADAS-Cog), and the Alzheimer’s Disease Cooperative Studies – Activities of Daily Living (ADCS-ADL) scale was used to monitor daily function. The Clinical Dementia Rating sum of Boxes (CDR-SB) was used to evaluate both cognitive and functional disability.

The 35-mg dose of RVT-101 was associated with a statistically significant improvement in cognition and function when administered as an adjunct to donepezil  vs placebo. Although the 15-mg dose of RVT-101 was associated with numerically improved values on the assessment scales, the differences were not statistically significant. 

The agent is particularly attractive due to its oral administration, once-daily dosing, lack of effect of food on pharmacokinetics, and low potential for drug-drug interactions. The investigators noted that RVT-101 was also well tolerated by the study participants.

The investigators report that the 35-mg dose of RVT-101 will be further assessed in an upcoming phase 3 study.


  1. Lombardo I. #DT-01-04. “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.” Oral presentation at: 2015 Alzheimer’s Association International Conference; Washington, DC; July 22, 2015.