Acadia Pharmaceuticals plans to start a Phase 3 clinical program to explore the effect of Nuplazid (pimavanserin) in Alzheimer’s disease patients with psychosis. The medication was approved by the U.S. Food and Drug Administration in April 2016 to treat similar problems with Parkinson’s patients.
“We’re very pleased with our strong start to 2017,” Acadia President and CEO Steve Davis said in a news release that also reported the company’s net revenue for the first quarter of 2017 at $15.3 million, a 28 percent increase from the fourth quarter of 2016.“We continue to advance our ongoing clinical studies in Alzheimer’s disease agitation, schizophrenia inadequate response, schizophrenia negative symptoms and major depressive disorder, and we look forward to moving our Alzheimer’s disease psychosis program into Phase III in the second half of 2017.”
Acadia, based in San Diego, has two ongoing trials for pimavanserin. The first, NCT03118947 is now recruiting patients to assess the drug’s safety and tolerability over 52 weeks of treatment in more than 400 patients with probable Alzheimer’s who have symptoms of agitation and aggression. The trial will likely end in 2020.
The SERENE trial (NCT02992132) is also recruiting patients and will evaluate the efficacy of pimavanserin to treat agitation and aggression compared with placebo after 12 weeks of treatment. The study plans to enroll about 400 patients and its primary endpoint is a reduction in total score on the Cohen-Mansfield Agitation Inventory (CMAI). After this trial ends in 2019, patients will be eligible to enroll in an open-label safety extension study.
Pimavanserin is a selective serotonin inverse agonist that preferentially targets the 5-HT2A receptors. This drug is approved in the United States to treat allucinations and delusions associated with Parkinson’s disease psychosis, under the brand name Nuplazid — an oral medicine taken once a day with a recommended dose of 34 mg (two 17-mg tablets).
Acadia sponsored a Phase 2 study (NCT02035553) investigating the safety and efficacy of pimavanserin in 181 patients (mean age 86 years) with Alzheimer’s disease psychosis. Patients were assigned to receive either 34 mg of pimavanserin or placebo once daily.
The study’s primary objective was the drug’s antipsychotic efficacy, which is measured by the mean change in the Neuropsychiatric Inventory-Nursing Home (NPI-NH) Psychosis score from study’s start to week 6 of treatment. Patients were dosed up to week 12 so that researchers could assess other endpoints, including cognition changes.
In December 2016, Acadia said patients treated with pimavanserin had a significant 3.76 point improvement in psychosis at week 6 compared to a 1.93 point improvement in patients receiving a placebo. This improvement was sustained up to week 12 but was no different from that of the placebo group at this point.
Also, after 12 weeks of treatment, there were no reports of impaired cognition associated with pimavanserin treatment, measured by the Mini-Mental State Examination (MMSE) score. Cognition was similar between both treatment arms. In terms of safety, pimavanserin was generally well-tolerated and the most common side effects included falls, urinary tract infection and agitation.