Data Confirmed Significant Improvement in Psychosis in Patients
with Alzheimer’s Disease with Substantively Greater Benefit in Patients
with More Severe Psychotic Symptoms
SAN DIEGO--(BUSINESS WIRE)--Nov. 3, 2017--
ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD), a biopharmaceutical company
focused on the development and commercialization of innovative medicines
to address unmet medical needs in central nervous system (CNS)
disorders, today announced the presentation of data from the Phase II
-019 Study of pimavanserin in Alzheimer’s disease psychosis at the 10th
Clinical Trials on Alzheimer’s Disease (CTAD) meeting in Boston. The
-019 Study data are being presented at the symposium titled, “The
Importance of Serotonin in Alzheimer’s Disease Psychosis and the Role of
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
FDA for dementia-related psychosis. In October 2017, the FDA granted
Breakthrough Therapy Designation for pimavanserin for the treatment of
“In the Phase II -019 Study, pimavanserin significantly reduced
psychosis in patients with Alzheimer’s disease without negatively
impacting cognition,” said Clive Ballard, MBChB, MRCPsych,
Pro-Vice-Chancellor and Executive Dean, University of Exeter Medical
School. “Pimavanserin also had a favorable tolerability profile compared
to known adverse effects of current antipsychotics. With no approved
treatment for dementia-related psychosis, there is a significant unmet
need. The results of the study indicate that pimavanserin could be an
important new treatment option for this elderly and underserved patient
Key Findings from the Phase II -019 Study Presented at CTAD Symposium
The Phase II -019 Study data are being presented by Clive Ballard in the
presentation titled, “Clinical Trial of Pimavanserin in Alzheimer’s
Disease Psychosis.” The Phase II -019 Study was a double-blind,
placebo-controlled trial designed to evaluate the efficacy and safety of
pimavanserin in 181 patients with Alzheimer’s disease psychosis.
Top-line results of the study were previously reported in December 2016.
Pimavanserin met the primary endpoint in the study, showing a
statistically significant reduction in psychosis versus placebo as
measured by the Neuropsychiatric Inventory-Nursing Home (NPI-NH)
Psychosis score at week 6 of dosing (delta = 1.84, p=0.0451, effect size
[Cohen’s d] = 0.32). The proportion of responders at week 6 that had an
NPI-NH Psychosis score improvement of ≥ 30% was 55.2% for
pimavanserin-treated patients versus 37.4% for placebo (p=0.0159).
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
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
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, University of
California, San Diego, titled, “The Role of 5-HT2A Receptors
in the Pharmacology of Alzheimer’s Disease Psychosis.” Serotonin 2A
receptors are highly expressed in brain regions critical for processing
sensory information and performing executive functions. Circuitry
performing these functions may be deregulated when neurodegeneration has
occurred. Selective 5-HT2A inverse agonists/antagonists can
be used to restore balance to these deregulated circuits. Pimavanserin
is a non-dopaminergic selective serotonin inverse agonist (SSIA)
preferentially targeting 5-HT2A receptors.
Furthermore, a presentation by Pierre N. Tariot, MD, Banner Alzheimer’s
Institute and University of Arizona College of Medicine, titled, “Review
of Pimavanserin Clinical Results in the Context of Historical
Alzheimer’s Disease Psychosis Trials,” reviews the results of the
pimavanserin Phase II -019 Study compared to Alzheimer’s disease
psychosis studies with other antipsychotics. Off-label use of atypical
antipsychotics is associated with modest and often equivocal efficacy
and significant acceleration in cognitive decline in patients with
dementia, as well as other adverse effects.
The symposium’s moderator is Jeffrey Cummings, MD, ScD, Director of
Cleveland Clinic Lou Ruvo Center for Brain Health, who reviews
epidemiology, clinical phenomenology and psycho-social consequences of
dementia-related psychosis and the current treatment options and
About Dementia-Related Psychosis
Around 8 million people in the United States are living with dementia,
of which around 5.5 million people suffer from Alzheimer’s disease.
Approximately half the people with dementia are diagnosed with the
disease. Studies suggest that approximately 30% of patients with
dementia have psychosis, commonly consisting of hallucinations and
delusions. 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, earlier progression
to nursing home care, more rapid progression of dementia, and increased
risk of morbidity and mortality.
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.
The FDA has granted Breakthrough Therapy Designation for pimavanserin
for the treatment of dementia-related psychosis. No drug is approved by
the FDA for dementia-related psychosis.
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 FDA in 2016 under the trade
name NUPLAZID®, and is the first and only medicine approved
for this indication. NUPLAZID is not approved for the treatment of
patients with dementia-related psychosis.
About ACADIA Pharmaceuticals
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 December 31, 2016 as well as ACADIA’s subsequent filings
with the Securities and Exchange Commission. You are cautioned not to
place undue reliance on these forward-looking statements, which speak
only as of the date hereof. This caution is made under the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995. All
forward-looking statements are qualified in their entirety by this
cautionary statement and ACADIA undertakes no obligation to revise or
update this press release to reflect events or circumstances after the
date hereof, except as required by law.
Important Safety Information and Indication for
NUPLAZID (pimavanserin) tablets
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
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
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
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
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
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.
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Source: ACADIA Pharmaceuticals Inc.
ACADIA Pharmaceuticals Inc.