- Study results consistent across different patient groups,
including those in long-term care facilities
Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) announced today that
the journal Drug Safety published results from a retrospective
analysis finding a lower mortality risk in patients with
Parkinson’s disease psychosis (PDP) treated with NUPLAZID®
(pimavanserin) compared to other atypical antipsychotics over 12
months and across various subgroups. NUPLAZID is the only
medication approved by the U.S. FDA for the treatment of
hallucinations and delusions associated with PDP.
“We were encouraged by this large, real-world study showing a
lower mortality risk in patients with PDP after initiation of
NUPLAZID, compared to other atypical antipsychotics. The robust
results were achieved across sub-groups and sensitivity analysis
using a variety of approaches,” said Ponni Subbiah, M.D., M.P.H.,
Senior Vice President, Global Head of Medical Affairs and Chief
Medical Officer, Acadia Pharmaceuticals. “These findings, along
with other recently published studies, will help physicians and the
patients they treat make decisions about managing Parkinson’s
disease psychosis symptoms that can be quite troubling and
disruptive to patients and their families, significantly impacting
their quality of life.”1,2
The retrospective, real-world, observational study evaluated a
cohort of patients identified using 2016-2019 Medicare claims data
who were 65 years of age and older in the United States and
diagnosed with Parkinson’s disease and psychosis, comparing those
who newly initiated NUPLAZID (n=2,892) or were prescribed an
off-label, comparator atypical antipsychotic (n=19,083; clozapine,
quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole).
After matching the two cohorts using propensity scores (PS), there
were 2,891 patients in each of the NUPLAZID and comparator cohorts.
In the matched cohorts, the hazard ratio (HR) for all-cause
mortality for NUPLAZID vs. comparator was 0.78 (95% CI, 0.67-0.91),
with the lowest time period-specific HRs in the first 180 days.
Researchers also evaluated a sub-cohort of the 30% of patients in
long-term care (LTC) or skilled nursing facilities (SNF) [matched
n=652 each for NUPLAZID and comparator cohorts]. Similarly, among
LTC and SNF residents, the HR was 0.78 (95% CI, 0.60-1.01).
Importantly, when mortality was evaluated separately within
subgroups, the HR estimates were consistent across all levels of
sex, age, and dementia diagnosis.
Non-motor symptoms of Parkinson’s disease, including
hallucinations and delusions associated with Parkinson’s disease
psychosis, can be more troublesome than motor symptoms.3 These
symptoms can also worsen over time, making it difficult for
patients to know whether or not what they are experiencing is
real.4,5 Psychosis is an important risk factor for mortality in
Parkinson’s disease. In a retrospective study evaluating the
association of death in patients with Parkinson’s disease compared
to PDP using Medicare data (2007-2015), mortality risk was 34%
greater when psychosis was present.6
This analysis observed real-world use of NUPLAZID approximately
3.5 years after its FDA approval and subsequent availability in the
United States. During this early period, patient characteristics
may have differed between NUPLAZID and comparator users, and
although matching balanced all measured characteristics, the
potential for residual confounding by unmeasured characteristics
remains. Additionally, the LTC/SNF sub-cohort analysis was limited
by the relatively small sample size.
About Parkinson’s Disease and Parkinson’s Disease Psychosis
Parkinson’s disease is a progressive nervous system disorder
that affects about one million people in the United States.7,8 The
signs and symptoms can vary with people experiencing both motor
symptoms and non-motor symptoms such as hallucinations (seeing,
hearing, or experiencing things that others don’t) and delusions
(false beliefs).5,9 Physicians may refer to these
Parkinson’s-related hallucinations and delusions as Parkinson’s
disease psychosis.5 Around 50 percent of people living with
Parkinson’s may experience hallucinations or delusions during the
course of their disease.9 Non-motor symptoms, as a whole, can be
more troublesome than motor symptoms, in terms of quality of life.3
Parkinson’s disease psychosis may add to the burden of caring for a
loved one with Parkinson’s disease.10,11
About NUPLAZID® (pimavanserin)
Pimavanserin is a selective serotonin inverse agonist and
antagonist preferentially targeting 5-HT2A receptors. These
receptors are thought to play an important role in neuropsychiatric
disorders. In vitro, pimavanserin demonstrated no appreciable
binding affinity for dopamine (including D2), histamine,
muscarinic, or adrenergic receptors. Pimavanserin was approved for
the treatment of hallucinations and delusions associated with
Parkinson’s disease psychosis by the U.S. Food and Drug
Administration in April 2016 under the trade name NUPLAZID. In
addition, Acadia is developing pimavanserin in other
neuropsychiatric conditions.
About Acadia Pharmaceuticals
Acadia is advancing breakthroughs in neuroscience to elevate
life. For more than 25 years we have been working at the forefront
of healthcare to bring vital solutions to people who need them
most. We developed and commercialized the first and only approved
therapy for hallucinations and delusions associated with
Parkinson’s disease psychosis. Our clinical-stage development
efforts are focused on treating the negative symptoms of
schizophrenia, Rett syndrome and neuropsychiatric symptoms in
central nervous system disorders. For more information, visit us at
www.acadia.com and follow us on LinkedIn and Twitter.
Important Safety Information and Indication for NUPLAZID®
(pimavanserin)
Indication
NUPLAZID is indicated for the treatment of hallucinations and
delusions associated with Parkinson’s disease psychosis.
Important Safety Information
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.
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.
Warnings and Precautions: 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 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:
- Coadministration with strong CYP3A4 inhibitors (e.g.,
ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to
10 mg taken orally as one tablet once daily.
- Coadministration with strong or moderate CYP3A4 inducers
reduces NUPLAZID exposure. Avoid concomitant use of strong or
moderate CYP3A4 inducers with NUPLAZID.
Dosage and Administration
Recommended dose: 34 mg capsule taken orally once daily, without
titration.
NUPLAZID is available as 34 mg capsules and 10 mg tablets.
Please read the full Prescribing Information including Boxed
WARNING.
Forward-Looking Statements
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 potential opportunity for future growth in sales of NUPLAZID;
the timing of ongoing and future clinical studies for pimavanserin;
the development and commercialization of trofinetide; and guidance
for full-year 2022 NUPLAZID net sales for Parkinson’s disease
psychosis only and certain expense line items. 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 uncertainty of
future commercial sales and related items that would impact net
sales during 2022, the risks and uncertainties inherent in drug
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, 2021 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.
References
1 Mosholder AD, Ma Y, Akhtar S, Podskalny GD, Feng Y, Lyu H,
Liao J, Wei Y, Wernecke M, Leishear K, Nelson LM, MaCurdy TE,
Kelman JA, Graham DJ. Mortality Among Parkinson's Disease Patients
Treated With Pimavanserin or Atypical Antipsychotics: An
Observational Study in Medicare Beneficiaries. Am J Psychiatry.
2022 Aug;179(8):553-561.
2 Pham Nguyen TP, Thibault D, Hamedani AG, Weintraub D, Willis
AW. Atypical antipsychotic use and mortality risk in Parkinson
disease. Parkinsonism Relat Disord. 2022 Oct;103:17-22.
3 Martinez-Martin P, Rodriguez-Blazquez C, et al. The Impact of
Non-Motor Symptoms on Health Related Quality of Life of Patients
with Parkinson’s Disease. Mov Disord. 2011;26(3):399-406.
4 Goetz, CG, Fan, W, Leurgans, S, et al. The malignant course of
“benign hallucinations” in Parkinson disease. Archives of
Neurology. 2006;63(5), 713–716.
5 Ravina B, Marder K, Fernandez HH, et al. Diagnostic criteria
for psychosis in Parkinson’s disease: report of an NINDS, NIMH work
group. Mov Disord. 2007 Jun 15;22(8):1061-8.
6 Wetmore JB, Li S, Yan H, et al. Increases in
institutionalization, healthcare resource utilization, and
mortality risk associated with Parkinson disease psychosis:
retrospective cohort study. Parkinsonism Relat Disord.
2019;68:95-101.
7 Parkinson’s Disease Foundation. What is Parkinson’s disease?
Retrieved from
https://www.parkinson.org/Understanding-Parkinsons/Statistics.
Accessed November 2022.
8 Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic
criteria for Parkinson’s disease. Mov Disord.
2015;30(12):1591-1601.
9 Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year
population-based study of psychosis in Parkinson’s disease. Arch
Neurol. 2010;67(8):996-1001.
10 Schrag A, Hovris A, et al. Caregiver-burden in parkinson’s
disease is closely associated with psychiatric symptoms, falls, and
disability. Parkinsonism and Related Disorders. 2006;12:35-41.
11 Aarsland D, Bronnick K, Ehrt U. et al. Neuropsychiatric
symptoms in patients with Parkinson’s disease and dementia:
frequency, profile and associated care giver stress. J Neurol
Neurosurg Psychiatry. 2007;78:36-42.
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version on businesswire.com: https://www.businesswire.com/news/home/20230103005162/en/
Media Contact: Acadia Pharmaceuticals Inc. Deb Kazenelson (818)
395-3043 media@acadia-pharm.com
Investor Contact: Acadia Pharmaceuticals Inc. Mark Johnson, CFA
(858) 261-2771 ir@acadia-pharm.com
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