Axovant Sciences has announced the preliminary results of a Phase 2 clinical trial testing the investigational oral drug therapy nelotanserin in patients with either dementia caused by Lewy bodies (DLB), or Parkinson’s disease dementia (PDD).
Nelotanserin is an investigational drug candidate that binds to a receptor of the central nervous system, called 5HT2A receptor, which has been implicated in mental disorders and is associated with neuropsychiatric disturbances, including visual hallucinations. Nelotanserin binds to the 5HT2A receptor, but prevents the receptor from activating its response. Researchers call this type of drug an inverse agonist.
The study is an ongoing Phase 2 trial where enrolled patients scored 18 or higher on Mini Mental State Examination (MMSE), a questionnaire extensively used in clinical and research settings to assess the level of patients’ cognitive impairment.
Enrolled participants were assigned randomly to a regimen that includes first a placebo followed by nelotanserin, or nelotanserin followed by placebo. Treatments went on for four weeks with either regimen, followed by a “washout” period (no therapy) again of four weeks. During treatment, participants are treated with 40 mg nelotanserin (two weeks) and then with 80 mg nelotanserin (two weeks).
The trial’s primary outcome goal included the drug’s safety and its effects on the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II + III, a scoring system widely used for the clinical evaluation of Parkinson’s disease. UPDRS Parts II + III was measured at two time-points, at baseline and at the end of each four-week treatment period.
Secondary outcome measures included alterations to the severity and frequency of visual hallucinations, as determined by the Scale for the Assessment of Positive Symptoms (SAPS).
The preliminary results showed a significant improvement in mean change from baseline in the UPDRS Parts II + III in participants treated with nelotanserin relative to placebo. Moreover, no drug-related serious adverse events were reported, as well as any case of discontinuation of the medication due to side effects. The assessed secondary endpoints showed no statistical significant differences between nelotanserin and placebo.
These preliminary results have prompted Axovant Sciences to continue to investigate nelotanserin effects, and for that reason they are expanding patient recruitment to confirm the initial benefits with nelotanserin treatment.
A Phase 3 registration program is due to begin in the second half of this year.
“I am intrigued by the benefits observed on the UPDRS in this study,” said James Leverenz, MD, chairman of the Scientific Advisory Council of the Lewy Body Dementia Association, in a press release. Leverenz also is director of the Cleveland Lou Ruvo Center for Brain Health at the Cleveland Clinic. “If a single drug could simultaneously address the motor and neuropsychiatric symptoms of Lewy body dementia, which the published literature suggests may be the case for 5HT2A antagonists, it would represent a unique and important advance for the treatment of this condition. I look forward to reviewing the full dataset later this year,” Leverenz said.
“We are pleased with the preliminary results of this small pilot study which supports our belief that nelotanserin could be a promising investigational drug candidate for patients suffering from Lewy body dementia,” added Lawrence Friedhoff, MD, PhD, and chief development officer of Axovant Sciences. “We plan to discuss with FDA and other regulators the parameters of a potential Phase 3 registration program while we await results from the full cohort of patients in this study. We will carefully examine whether the UPDRS treatment benefit observed in this interim analysis will be maintained in the final analysis when the remaining patients complete this study.”