ACADIA Pharmaceuticals announced the initiation of HARMONY, a Phase III study to evaluate pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis, a serious medical condition for which there is no therapy approved by the U.S. Food and Drug Administration (FDA). The company also announced that the FDA has granted Breakthrough Therapy Designation to pimavanserin for dementia-related psychosis. Dementia-related psychosis includes psychosis in patients with Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia.
If the clinical development program is successful, and pimavanserin is ultimately approved by the FDA for the treatment of dementia-related psychosis, it would represent a significant expansion of the approved use of pimavanserin. Currently, pimavanserin is the only drug approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. It is marketed under the trade name NUPLAZID®.
“We are pleased the FDA has agreed to an efficient development path for pimavanserin in this broad indication and granted Breakthrough Therapy Designation in recognition of this serious unmet need,” said Serge Stankovic, M.D., M.S.P.H., ACADIA’s Executive Vice President, Head of Research and Development. “Initiation of our Phase III study is supported by clinical and preclinical evidence of pimavanserin’s antipsychotic activity without detrimental effects on cognitive function or other side effects associated with antipsychotics currently used off-label for this indication.”
Around 8 million people in the United States are living with dementia and approximately half are diagnosed with the disease. Studies suggest that approximately 30% of patients with dementia have psychosis, commonly consisting of hallucinations and delusions. Serious consequences have been associated with severe or persistent psychosis in patients with dementia such as repeated hospital admissions, earlier progression to nursing home care, more rapid progression of dementia, and increased risk of morbidity and mortality.
“With receipt of FDA’s Breakthrough Therapy Designation for pimavanserin, we are able to accelerate this important program,” said Steve Davis, President and Chief Executive Officer of ACADIA. “Pimavanserin has a unique biological mechanism that distinguishes it from any other antipsychotic. We believe the profile we observed in our Phase II -019 Study in Alzheimer’s disease psychosis could be particularly beneficial in this elderly underserved population. In that study, pimavanserin demonstrated antipsychotic effect without impairing cognition and we also observed a very favorable tolerability profile. We were very excited to be the first and only FDA approved drug for the treatment of Parkinson’s disease psychosis and are equally excited about the potential to help many more patients suffering from dementia-related psychosis.”
The initiation of the pivotal study in dementia-related psychosis, referred to as HARMONY, follows an End-of-Phase II Meeting and agreement with the FDA on the clinical development plan and the design of the Phase III study. ACADIA believes that robust positive results from one Phase III study together with supportive data from prior studies with pimavanserin could serve as the basis of a supplementary New Drug Application (sNDA) for the treatment of hallucinations and delusions associated with dementia-related psychosis.
Breakthrough Therapy Designation serves to expedite the development and review by the FDA of drugs that are intended to treat a serious or life-threatening disease or condition. The Breakthrough Therapy Designation for dementia-related psychosis was granted, in part, based on results of ACADIA’s Phase II -019 Study with pimavanserin in Alzheimer’s disease psychosis and results of the company’s Phase III -020 Study with pimavanserin in Parkinson’s disease psychosis. This is the second Breakthrough Therapy Designation for pimavanserin.
About the Phase III HARMONY Study
HARMONY is a Phase III, randomized, double-blind, placebo-controlled study, evaluating the efficacy and safety of pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis. The objective of the study is to evaluate the ability of pimavanserin to prevent relapse of psychotic symptoms in a broad population of patients with the most common subtypes of dementia: Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia and frontotemporal dementia. The study will be conducted globally and is expected to enroll approximately 360 patients.
The study includes a 12-week open-label stabilization period during which patients with dementia-related psychosis will be treated with pimavanserin 34 mg once daily. Dose reduction to 20 mg once daily will be allowed if clinically justified. Following the 12-week stabilization period, patients who meet pre-specified criteria for treatment response will then be randomized into the double-blind period of the study to continue their pimavanserin dose (34 mg or 20 mg per day) or be switched to placebo and followed for up to 26 weeks or until a relapse of psychosis occurs. The primary endpoint in the study is time to relapse in the double-blind period.
Clinical Data Supporting Phase III Trial Design
The Phase III development plan is supported by data from two completed clinical studies. As previously announced, in the completed Phase II -019 Study of pimavanserin in Alzheimer’s disease psychosis, pimavanserin demonstrated clinically meaningful and statistically significant efficacy of pimavanserin 34 mg over placebo on the primary endpoint as measured by the Neuropsychiatric Inventory-Nursing Home (NPI-NH) psychosis score at week 6 of dosing (p=0.0451). Results from this Phase II study in Alzheimer’s disease psychosis will be presented at the 10th Clinical Trials on Alzheimer’s Disease (CTAD) Meeting on November 3, 2017 in Boston.
Additional clinical evidence for efficacy of pimavanserin in dementia-related psychosis was observed in the Phase III -020 Study in patients with Parkinson’s disease psychosis. Approximately a quarter of the patients enrolled in the -020 Study also suffered from mild dementia. In a pre-specified subgroup analysis of these patients, those treated with pimavanserin observed a significant improvement in psychosis compared to placebo. This effect was larger than the overall average effect observed in the study.