ACADIA Pharmaceuticals Initiates Phase III Study of Pimavanserin in 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
- FDA Grants Breakthrough Therapy Designation to Pimavanserin for Dementia-Related Psychosis
Conference Call to Be Held Today at
5:00 pm ETto Discuss Phase III Development Program
If the clinical development program is successful, and pimavanserin is
ultimately approved by the
“We are pleased the
Around 8 million people in
“With receipt of FDA’s Breakthrough Therapy Designation for
pimavanserin, we are able to accelerate this important program,” said
The initiation of the pivotal study in dementia-related psychosis,
referred to as HARMONY, follows an End-of-Phase II Meeting and agreement
Breakthrough Therapy Designation serves to expedite the development and
review by the
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
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.
ACADIA also announced that due to the potential overlap of clinical sites and study participants between its Phase III HARMONY dementia-related psychosis study and the Company’s ongoing Phase II SERENE study of pimavanserin in Alzheimer’s disease agitation, it has decided to discontinue enrollment of new patients in the SERENE study. Patients already enrolled will complete the study as planned. Discontinuation of enrollment in the SERENE study will avoid potential interference between the two studies and enable ACADIA to focus external and internal resources on the Phase III dementia-related psychosis program.
Conference Call and Webcast Information
ACADIA management will hold a conference call and webcast today at
Pimavanserin is a selective serotonin inverse agonist (SSIA)
preferentially targeting 5-HT2A receptors. These receptors
are thought to play an important role in dementia-related psychosis.
Pimavanserin is being evaluated in an extensive clinical development
program by ACADIA across multiple indications. Pimavanserin (34 mg) was
approved for the treatment of hallucinations and delusions associated
with Parkinson’s disease psychosis by the
About Dementia-Related Psychosis
Around 8 million people in
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 maintains a website at www.acadia-pharm.com to which we regularly post copies of our press releases as well as additional information and through which interested parties can subscribe to receive e-mail alerts.
Statements in this press release that are not strictly historical in
nature are forward-looking statements. These statements include but are
not limited to statements related to the benefits to be derived from
NUPLAZID (pimavanserin); the utility of pimavanserin in indications
other than hallucinations and delusions associated with Parkinson’s
disease psychosis, including indications falling within dementia-related
psychosis; whether the profile observed in the Phase II -019 Study in
Alzheimer’s disease psychosis will be beneficial to elderly patients
with dementia-related psychosis; whether the development path for
dementia-related psychosis will be efficient; whether NUPLAZID will
receive a broad indication for dementia-related psychosis; whether the
approved use of NUPLAZID will be significantly expanded; whether
positive results from one Phase III study of pimavanserin in
dementia-related psychosis will be sufficient basis for the filing or
approval of an sNDA for that indication; the timing of presentation of
clinical data and results; and the timing or results of future studies
involving pimavanserin. These statements are only predictions based on
current information and expectations and involve a number of risks and
uncertainties. Actual events or results may differ materially from those
projected in any of such statements due to various factors, including
the risks and uncertainties inherent in drug discovery, development,
approval and commercialization, and the fact that past results of
clinical trials may not be indicative of future trial results. For a
discussion of these and other factors, please refer to ACADIA’s annual
report on Form 10-K for the year ended
Important Safety Information and Indication for
NUPLAZID (pimavanserin) tablets
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.
NUPLAZID is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
Contraindication: NUPLAZID is contraindicated in patients with a history of hypersensitivity reaction to pimavanserin or any of its components. Reactions have included rash, urticaria, tongue swelling, circumoral edema, and throat tightness.
QT Interval Prolongation: NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics. NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
Adverse Reactions: The most common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).
Drug Interactions: Strong CYP3A4 inhibitors (eg, ketoconazole) increase NUPLAZID concentrations. Reduce the NUPLAZID dose by one-half. Strong CYP3A4 inducers may reduce NUPLAZID exposure, monitor for reduced efficacy. Increase in NUPLAZID dosage may be needed.
Renal Impairment: No dosage adjustment for NUPLAZID is needed in patients with mild to moderate renal impairment. Use of NUPLAZID is not recommended in patients with severe renal impairment.
Hepatic Impairment: Use of NUPLAZID is not recommended in patients with hepatic impairment. NUPLAZID has not been evaluated in this patient population.
Pregnancy: Use of NUPLAZID in pregnant women has not been evaluated and should therefore be used in pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
Pediatric Use: Safety and efficacy have not been established in pediatric patients.
Dosage and Administration: Recommended dose: 34 mg per day, taken orally as two 17-mg tablets once daily, without titration.
For additional Important Safety Information, including boxed warning, please see the full Prescribing Information for NUPLAZID at https://www.nuplazid.com/pdf/NUPLAZID_Prescribing_Information.pdf.