9 September 2019 - - US-based Acadia Pharmaceuticals Inc.'s (NASDAQ: ACAD) Phase 3 HARMONY study, a double-blind, placebo-controlled relapse prevention trial evaluating pimavanserin for the treatment of dementia-related psychosis, met its primary endpoint, demonstrating a highly statistically significant longer time to relapse of psychosis with pimavanserin compared to placebo in a planned interim efficacy analysis, the company said.

Upon the recommendation of the study's independent data monitoring committee, which met to review the data from the planned interim efficacy analysis, the study will now be stopped early based on pre-specified stopping criteria requiring a one-sided p-value less than 0.0033 on the study's primary endpoint.

The company is planning to meet with the FDA regarding a supplemental NDA submission in 2020 and the results from the HARMONY study will be submitted for presentation at upcoming medical meetings.

The FDA previously granted Breakthrough Therapy Designation for pimavanserin for the treatment of dementia-related psychosis.

No drug is approved by the FDA for the treatment of dementia-related psychosis.

HARMONY is a Phase 3 study designed to evaluate the efficacy and safety of pimavanserin for the treatment of delusions and hallucinations associated with dementia-related psychosis across a broad population of patients with the most common subtypes of dementia including: Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, vascular dementia, and frontotemporal dementia spectrum disorders.

The HARMONY study included a 12-week open-label stabilization period during which patients with dementia-related psychosis were treated with pimavanserin 34 mg once daily. Dose reduction to 20 mg once daily was allowed if clinically justified within the first four weeks.

Following the 12-week stabilization period, patients who met pre-specified criteria for treatment response were then randomised into the double-blind period of the study to continue their pimavanserin dose (34 mg or 20 mg per day) or switched to placebo and followed for up to 26 weeks or until a relapse of psychosis occurred.

The primary endpoint in the study was time to relapse in the double-blind period.

Relapse (significant worsening of dementia-related psychosis after prior stabilization) was defined in the study by one or more of the following: hospitalisation due to dementia-related psychosis, significant deterioration of dementia-related symptoms on clinical scales, withdrawal from the study due to lack of efficacy, or the use of an off-label antipsychotic medication for the treatment of dementia-related delusions and/or hallucinations.

All potential relapses and discontinuations in the double-blind portion of the study were adjudicated by an independent adjudication committee to determine if protocol defined relapse criteria were met.

Around 8m people in the United States are living with dementia and studies suggest that approximately 30% of dementia patients, or 2.4m people, have psychosis, commonly consisting of delusions and hallucinations.

Dementia-related psychosis includes psychosis in Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, vascular dementia, and frontotemporal dementia.

Serious consequences have been associated with severe or persistent psychosis in patients with dementia such as repeated hospital admissions, increased likelihood of nursing home placement, progression of dementia, and increased risk of morbidity and mortality.

Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors.

These receptors are thought to play an important role in psychosis, schizophrenia, depression and other neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors.

Acadia is evaluating pimavanserin in an extensive clinical development program across multiple indications with significant unmet need including dementia-related psychosis, adjunctive major depressive disorder, and the negative symptoms of schizophrenia.

Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis by the US Food and Drug Administration in April 2016 under the trade name NUPLAZID.

Nuplazid is not approved for dementia-related psychosis, schizophrenia or major depressive disorder.

Acadia is a biopharmaceutical company focused on the development and commercialization of innovative medicines to address unmet medical needs in central nervous system disorders. ACADIA has developed and commercialized the first and only medicine approved for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.

Acadia also has ongoing clinical development efforts in additional areas with significant unmet need, including dementia-related psychosis, major depressive disorder, the negative symptoms of schizophrenia, and Rett syndrome.