ACADIA Pharmaceuticals Presents Data from the Phase II Study of Pimavanserin in Alzheimer’s Disease Psychosis at the Clinical Trials on Alzheimer’s Disease (CTAD) 2017 Meeting
Data Confirmed Significant Improvement in Psychosis in Patients with Alzheimer’s Disease with Substantively Greater Benefit in Patients with More Severe Psychotic Symptoms
Pimavanserin met the primary endpoint in the Phase II -019 Study,
showing a statistically significant reduction in psychosis versus
placebo, as previously reported. Data presented at CTAD showed multiple
sensitivity and responder analyses supportive of the primary result and
demonstrated substantively greater benefit in those patients with more
severe psychosis. Building on these data, ACADIA recently initiated the
Phase III HARMONY study of pimavanserin in dementia-related psychosis.
Dementia-related psychosis includes psychosis in Alzheimer’s disease,
dementia with Lewy bodies, Parkinson’s disease dementia, vascular
dementia, and frontotemporal dementia. There is no drug approved by the
“In the Phase II -019 Study, pimavanserin significantly reduced
psychosis in patients with Alzheimer’s disease without negatively
impacting cognition,” said
Key Findings from the Phase II -019 Study Presented at CTAD Symposium
The Phase II -019 Study data are being presented by
Pimavanserin met the primary endpoint in the study, showing a
statistically significant reduction in psychosis versus placebo as
measured by the
Importantly, in the -019 Study, no detrimental effect was observed on cognition for pimavanserin-treated patients compared to placebo. Atypical antipsychotics have been associated with a statistically significant acceleration of cognitive deterioration in patients with Alzheimer’s disease.
The pimavanserin and placebo groups did not separate statistically on the secondary endpoints of the Alzheimer’s Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) or the Cohen-Mansfield Agitation Inventory Short Form (CMAI-SF), nor on the exploratory endpoints of the mean change in NPI-NH Psychosis score at week 12 or the Alzheimer’s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL).
Data presented at CTAD from a pre-specified subgroup analysis demonstrated a substantively larger and significant reduction in psychosis in pimavanserin-treated patients with more severe psychosis, further underscoring the effect seen on the primary result. Approximately one-third of patients in the study had more severe psychotic symptoms (NPI-NH Psychosis score ≥12). In this subgroup, pimavanserin demonstrated a statistically significant reduction in psychosis versus placebo on the NPI-NH Psychosis score at week 6 (delta = 4.43, p=0.0114, effect size [Cohen’s d] = 0.73). Additionally, the proportion of responders at week 6 that had an NPI-NH Psychosis score improvement of ≥ 30% was 88.9% for pimavanserin-treated patients versus 43.3% for placebo (p=0.0004).
Larger effects were also observed on the NPI-NH Psychosis score in pimavanserin-treated patients with prior antipsychotic use.
As previously reported, pimavanserin was well tolerated in this frail and elderly population and the safety profile was consistent with what has been observed in previous studies.
Other Presentations at CTAD Symposium: “The Importance of Serotonin in Alzheimer’s Disease Psychosis and the Role of Pimavanserin”
The -019 Study data are being presented as part of a three-part
symposium. The symposium also includes a presentation by Stephen M.
Stahl, MD, PhD, Adjunct Professor of Psychiatry,
Furthermore, a presentation by
The symposium’s moderator is
About Dementia-Related Psychosis
Around 8 million people in
Phase III HARMONY Study
Pimavanserin is currently being evaluated in a Phase III study, HARMONY, which is designed to evaluate its efficacy and safety 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.
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
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 pimavanserin could be an important new treatment for
elderly and underserved patients with dementia-related psychosis;
whether selective 5-HT2A inverse agonists/antagonists, such as
pimavanserin, can be used to restore balance to brain regions critical
for processing sensory information and performing executive functions;
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 a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported.
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.