- Pimavanserin as an adjunct to an
antipsychotic showed significant improvements in the negative
symptoms of schizophrenia vs. antipsychotic treatment alone
- Pimavanserin well-tolerated among study
participants
Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) announced today that
The Lancet Psychiatry published results from the Phase 2 ADVANCE
study. ADVANCE was an international, 26-week, randomized,
double-blind, placebo-controlled study evaluating the efficacy and
safety of adjunctive pimavanserin treatment in outpatients with
moderate-to-severe predominant negative symptoms of schizophrenia
who had achieved control of positive symptoms with their ongoing
antipsychotic treatment.
ADVANCE met its primary endpoint, with significant improvement
observed with pimavanserin for the change from baseline to week 26
on the Negative Symptoms Assessment-16 (NSA-16) total score,
compared with placebo (-10.4 vs. -8.5; p=0.043). In a post hoc
analysis, greater improvement in the NSA-16 total score compared to
placebo was observed in the 53.8% of patients (n=107) who received
the highest pimavanserin dose of 34 mg (-11.6 vs. -8.5; unadjusted
p=0.0065).
“Negative symptoms of schizophrenia are associated with higher
overall morbidity and decreased functioning, and there are no
approved treatments,” said Dragana Bugarski-Kirola, M.D., MBA,
MSci, Vice President, Clinical Development, Acadia Pharmaceuticals,
GmbH. “These findings lend confidence in our continued evaluation
of pimavanserin for the treatment of negative symptoms of
schizophrenia. We look forward to sharing results of the ongoing,
similarly-designed, Phase 3 ADVANCE-2 study, evaluating
pimavanserin 34 mg in patients with predominant negative symptoms
of schizophrenia.”
In the study, pimavanserin was well-tolerated with high
completion rates of approximately 86% in both the pimavanserin and
placebo treatment groups through 26 weeks and similar rates of
adverse events between pimavanserin (39.8%) and placebo (35.1%).
Additionally, no clinically significant differences in vital signs,
weight, metabolic syndrome or extrapyramidal symptoms were observed
in the pimavanserin group compared to placebo. Serious adverse
events were reported in 2.0% of patients on pimavanserin and 0.5%
of patients on placebo and discontinuations due to adverse events
were also low, 5.0% for pimavanserin and 3.0% for placebo.
“The clinically and
statistically significant improvement in negative symptoms of
schizophrenia with pimavanserin as an adjunctive treatment with
other antipsychotics, combined with the observed favorable
tolerability profile, suggest pimavanserin may offer a promising
approach in treating negative symptoms of schizophrenia, a severe
and difficult condition to treat and significant area of unmet need
for patients,” said Henry Nasrallah, M.D., study co-author,
Professor-Emeritus, Psychiatry & Behavioral Neuroscience,
University of Cincinnati College of Medicine, Cincinnati,
Ohio.
The ADVANCE study is available here.
About ADVANCE
The Phase 2 ADVANCE study was a 26-week, randomized,
double-blind, placebo-controlled, multi-center, international study
designed to examine the efficacy and safety of pimavanserin in
patients with schizophrenia who have predominant negative symptoms
while on a stable background antipsychotic therapy. 403 patients
were randomized to receive once-daily pimavanserin (n=201) or
placebo (n=202) as an adjunct treatment to their ongoing
antipsychotic in a flexible dosing regimen. The starting daily dose
of 20 mg of pimavanserin at baseline could have been adjusted to 34
mg or 10 mg during the first eight weeks of treatment. 53.8% of
patients who were randomized to receive pimavanserin completed the
trial on 34 mg, 44.7% on 20 mg, and 1.5% on 10 mg. The primary
endpoint of the study was the change from baseline to week 26 on
the Negative Symptom Assessment-16 (NSA-16) total score.
Baseline characteristics were similar across two treatment arms.
The most prevalent background antipsychotics in the study included
risperidone (38.5%), aripiprazole (32.5%), and olanzapine (28.0%).
The average age of patients in the study was 37.2 years.
About Schizophrenia and Negative Symptoms
According to the National Mental Health Institute, approximately
one percent of the U.S. population develops schizophrenia during
their lifetime.1 Schizophrenia is a chronic, debilitating and often
progressive mental illness characterized by disturbances in
thinking, emotional reaction, and behavior. These disturbances may
include positive symptoms, such as hallucinations and delusions,
and a range of negative symptoms, including loss of interest,
emotional withdrawal, and cognitive disturbances.
Studies show that about 40 to 50 percent of schizophrenia
patients suffer from predominant negative symptoms.2 While
currently available antipsychotic treatments for schizophrenia
target positive symptoms, most patients remain functionally
impaired because of negative symptoms, cognitive deficits, and
limited social function. Negative symptoms have been shown to
impair patient outcomes, e.g., personal relationships, household
and work performance and lower quality of life.3,4,5 Negative
symptoms have also been shown to be associated with an increased
likelihood of relapse and hospital admission, as well as a longer
duration of hospital admissions.3,6
About 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 psychiatric and
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®.
NUPLAZID is not approved for treatment of negative symptoms of
schizophrenia. In addition, Acadia is developing pimavanserin in
other psychiatric and neuropsychiatric conditions.
About Acadia Pharmaceuticals
Acadia is trailblazing 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 late-stage development efforts
are focused on dementia-related psychosis, negative symptoms of
schizophrenia and Rett syndrome, and in early-stage clinical
research we are exploring novel approaches to pain management, and
cognition and neuropsychiatric symptoms in central nervous system
disorders. For more information, visit us at www.acadia-pharm.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%).
- 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 regarding the
timing of future events. 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 development, approval and commercialization. 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, 2020 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
1NAMI, Mental Help, PsyCom, SAMHSA study, NIMH data
consolidation.
2Patel et al. 2015; Haro et al. 2015; Bobes et al. 2010; Chue
and Lalonde, 2014.
3Patel R, Jayatilleke N, Broadbent M, et al. Negative symptoms
in schizophrenia: a study in a large clinical sample of patients
using a novel automated method. BMJ Open 2015 Sep
7;5(9):e007619.
4Andrianarisoa M, Boyer L, Godin O, et al. Childhood trauma,
depression and negative symptoms are independently associated with
impaired quality of life in schizophrenia. Results from the
national FACE-SZ cohort. Schizophr Res. 2017;185:173-81.
5Milev P, Ho BC, Arndt S, et al. Predictive values of
neurocognition and negative symptoms on functional outcome in
schizophrenia: a longitudinal first-episode study with 7-year
follow-up. Am J Psychiatry. 2005;162:495-506.
6Bowtell M, Ratheesh A, McGorry P, et al. Clinical and
demographic predictors of continuing remission or relapse following
discontinuation of antipsychotic medication after a first episode
of psychosis. A systematic review. Schizophr Res.
2018;197:9-18.
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version on businesswire.com: https://www.businesswire.com/news/home/20211201005246/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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