Acadia Pharmaceuticals Receives Complete Response Letter from U.S. FDA for Supplemental New Drug Application for Pimavanserin for the Treatment of Hallucinations and Delusions Associated with Alzheimer’s Disease Psychosis
August 04 2022 - 11:05PM
Business Wire
Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that
the Company has received a Complete Response Letter (CRL) from the
U.S. Food and Drug Administration (FDA) regarding its supplemental
New Drug Application (sNDA) for NUPLAZID® (pimavanserin) for the
treatment of hallucinations and delusions associated with
Alzheimer’s disease psychosis (ADP).
The CRL indicated that the FDA has completed review of the
application, determining that it could not approve the sNDA in its
present form, and recommended that Acadia conduct an additional
trial in ADP. While the FDA stated that Study 019 demonstrated a
statistically significant treatment effect on its primary endpoint,
they concluded that there are limitations in the interpretability
of the 019 results. The FDA also stated that the positive treatment
effect of pimavanserin on dementia-related psychosis in Study 045
(HARMONY) appeared to be driven by the robustly positive results in
the Parkinson’s disease dementia subgroup, a condition they stated
is subsumed within the currently approved NUPLAZID Parkinson’s
disease psychosis (PDP) indication. Up to 50 percent of PDP
patients have dementia.1
“We are disappointed with this outcome. The treatment of
Alzheimer’s disease psychosis continues to be an area of high unmet
need, for which there is no approved therapy,” said Steve Davis,
Chief Executive Officer. “We want to express our gratitude to all
of the patients, their families and investigators who have
participated in our clinical trials.”
NUPLAZID was approved in the U.S. in 2016 and is the first and
only treatment for hallucinations and delusions associated with
PDP.
About Alzheimer’s Disease Psychosis
According to the Alzheimer’s Association, approximately six
million people in the United States are living with Alzheimer’s
disease (AD).2-3 Approximately 30% of patients with AD experience
psychosis, commonly consisting of hallucinations and delusions.4
These symptoms may be frequent and severe and may recur over time.5
A hallucination is defined as a perception-like experience that
occurs without an external stimulus and is sensory (seen, heard,
felt, tasted, sensed, smelled) in nature. A delusion is defined as
a false, fixed belief despite evidence to the contrary. Serious
consequences have been associated with psychosis in patients with
dementia, such as increased likelihood of nursing home placement,
more severe dementia, and increased risk of morbidity and
mortality.6-7 There is no FDA approved drug for the treatment of
Alzheimer’s disease psychosis.
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 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 Alzheimer’s disease psychosis. 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 late-stage development efforts
are focused on the negative symptoms of schizophrenia and Rett
syndrome. Our early-stage development efforts are focused on novel
approaches to pain management, cognition 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
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 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, 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 Holt RJ et al. Prevalence of Parkinson’s disease-induced
psychosis in a large U.S. managed care population. J
Neuropsychiatry Clin Neurosci. 2010; 22(1): 105-110. 2 Alzheimer’s
Association. 2021 Alzheimer’s Disease Facts and Figures.
Alzheimer’s Dement. 2021; 16(3): 391. 3 Rajan KB et al. Population
estimate of people with clinical Alzheimer’s disease and mild
cognitive impairment in the United States (2020-2060). Alzheimer’s
and Dementia. 2021: 1-10. 4 Cummings J et al. Criteria for
Psychosis in Major and Mild Neurocognitive Disorders: International
Psychogeriatric Associations (IPA) Consensus Clinical and Research
Definition. Am J of Geriatric Psychiatry. 2020; 28(12): 1256-1269.
5 Ballard C et al. A prospective study of psychotic symptoms in
dementia sufferers: psychosis in dementia. Int Psychogeriatr. 1997;
9(1): 57-64. 6 Scarmeas N et al. Delusions and hallucinations are
associated with worse outcome in Alzheimer Disease. Arch Neurol.
2005; 62(10): 1601-1608. 7 Peters ME et al. Neuropsychiatric
symptoms as predictors of progression to severe Alzheimer’s
dementia and death: the Cache County Dementia Progression study. Am
J Psychiatry. 2015; 172(5): 460-465.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220804006095/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
Acadia Pharmaceuticals (NASDAQ:ACAD)
Historical Stock Chart
From Aug 2024 to Sep 2024
Acadia Pharmaceuticals (NASDAQ:ACAD)
Historical Stock Chart
From Sep 2023 to Sep 2024