- Submission based on positive results from the
Phase 3 HARMONY study which showed a statistically significant 2.8
fold reduction in the risk of relapse of psychosis
ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD) announced today that
the company submitted a supplemental New Drug Application (sNDA) to
the U.S. Food and Drug Administration (FDA) to support a potential
new indication for NUPLAZID® (pimavanserin) for the treatment of
hallucinations and delusions associated with dementia-related
psychosis (DRP). The FDA previously granted Breakthrough Therapy
Designation for pimavanserin for the treatment of hallucinations
and delusions associated with DRP.
“This is an important step forward for the approximately 2.4
million people in the U.S. who suffer from dementia-related
hallucinations and delusions, representing a large unmet need with
currently no approved treatment options,” said Steve Davis,
ACADIA’s Chief Executive Officer. “Our pivotal HARMONY study showed
a meaningful reduction of the symptoms and stabilization of
psychosis and a nearly three-fold reduction in the risk of relapse
of psychosis for patients continuing treatment on pimavanserin
compared to placebo. We look forward to working with the FDA as it
reviews our submission.”
The sNDA is supported by results from the pivotal Phase 3
HARMONY study, which met its primary endpoint, demonstrating that
pimavanserin significantly reduced the risk of relapse of psychosis
by 2.8 fold compared to placebo (hazard ratio = 0.353; one-sided
p=0.0023). The sNDA also includes positive efficacy results from
two additional placebo-controlled studies, both of which met their
respective primary endpoints: The Phase 2 (-019) study in patients
with Alzheimer’s disease psychosis and the Phase 3 (-020) study in
patients with Parkinson’s disease psychosis. The sNDA includes a
large safety and tolerability database from completed and ongoing
studies representing over 1500 patients with neurodegenerative
disease.
Dementia is highly prevalent, affecting approximately 8 million
people in the U.S., and is only expected to grow as the population
ages. Approximately 30 percent, or 2.4 million people, experience
dementia-related psychosis and only half, or 1.2 million, are
diagnosed and treated1,2.
NUPLAZID was approved in the U.S. in 2016 as the first and only
treatment for hallucinations and delusions associated with
Parkinson’s disease psychosis. If approved by the FDA, NUPLAZID
would be the first drug approved to treat the hallucinations and
delusions associated with dementia-related psychosis and would be
the second indication for NUPLAZID.
About HARMONY
HARMONY was a Phase 3 study designed to evaluate the efficacy
and safety of pimavanserin for the treatment of hallucinations and
delusions associated with dementia-related psychosis across a broad
population of patients with the most common clinically diagnosed
subtypes of dementia including: Alzheimer’s disease, dementia with
Lewy bodies, Parkinson’s disease dementia, vascular dementia, and
frontotemporal dementia spectrum disorders. A total of 392 patients
were enrolled in the study, with an average age of 74.5 years and a
mean Mini-Mental State Examination (MMSE) score of 16.7. The
primary endpoint in the study was time to relapse in the
double-blind period as represented by the Kaplan-Meier curve and
the hazard ratio. Top-line results were presented at the 2019
Clinical Trials on Alzheimer’s Disease (CTAD) Meeting in December
2019.
The HARMONY study included a 12-week open-label stabilization
period during which patients with dementia-related psychosis began
treatment with pimavanserin 34 mg once daily. In the open-label
period, a significant majority (61.8%) of eligible subjects (N=351)
met the sustained treatment response criteria at Week 8 and Week 12
and entered the double-blind period. Following the open-label
period, patients who met pre-specified criteria for treatment
response were then randomized into the double-blind period of the
study to continue their pimavanserin dose (34 mg or 20 mg per day)
or switched to placebo and followed for up to 26 weeks or until a
relapse of psychosis occurred. Pimavanserin met its primary
endpoint and was stopped at the pre-planned interim analysis for
positive efficacy, demonstrating that pimavanserin significantly
reduced the risk of relapse of psychosis by 2.8 fold compared to
placebo (hazard ratio = 0.353; one-sided p=0.0023).
Pimavanserin was well-tolerated over the entire nine-month study
duration, and pimavanserin treatment was not associated with a
decline in cognition, as measured by the MMSE score, or the onset
or worsening of extrapyramidal symptoms, as measured by the
Extrapyramidal Symptom Rating Scale A (ESRS-A) score, compared to
placebo. In the double-blind period, low rates of adverse events
were observed, 41.0% of patients on pimavanserin and 36.6% on
placebo. Discontinuations in the double-blind period due to adverse
events were low, 2.9% for pimavanserin and 3.6% for placebo. Rates
of serious adverse events were also low, 4.8% in the pimavanserin
group and 3.6% in the placebo group. One death was reported in the
open-label period and one death was reported in the pimavanserin
group during the double-blind period. Investigators determined
neither death was related to the study drug.
About Dementia-Related Psychosis
Approximately 8 million people in the United States are living
with dementia, a condition with a core feature of declining
cognition (changes in memory, decision-making abilities, language,
etc.) resulting in functional impairment. Dementia is a
manifestation of an underlying condition which is often progressive
and neurodegenerative in nature.3 In addition to cognitive decline,
dementing illnesses almost universally lead to neuropsychiatric
symptoms, including hallucinations, delusions, and changes in
behavior.
It is estimated that 2.4 million Americans (or 30% of people
with dementia) experience dementia-related hallucinations and
delusions1,2. These symptoms may be frequent and severe and may
recur over time. A delusion is defined as a false, fixed belief
that is resolutely held despite evidence to the contrary. A
hallucination is defined as a perception-like experience that
occurs without an external stimulus and is sensory (seen, heard,
felt, tasted, sensed) in nature. Dementia-related psychosis occurs
in many types of dementia, including Alzheimer’s disease, dementia
with Lewy bodies, Parkinson’s disease dementia, vascular dementia,
and frontotemporal dementia. Serious consequences have been
associated with psychosis in patients with dementia, such as
repeated hospital admissions, increased likelihood of nursing home
placement, faster progression of dementia, and increased risk of
morbidity and mortality4.
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 psychosis,
schizophrenia, depression and other neuropsychiatric disorders. In
vitro, pimavanserin demonstrated no appreciable binding affinity
for dopamine (including D2), histamine, muscarinic, or adrenergic
receptors. ACADIA is evaluating pimavanserin in an extensive
clinical development program in multiple indications with
significant unmet need, including dementia-related psychosis, major
depressive disorder, and negative symptoms of schizophrenia.
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 dementia-related psychosis,
schizophrenia or major depressive disorder.
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 has
developed and commercialized the first and only medicine approved
for the treatment of hallucinations and delusions associated with
Parkinson’s disease psychosis. ACADIA also has ongoing clinical
development efforts in additional areas with significant unmet
need, including dementia-related psychosis, the negative symptoms
of schizophrenia, major depressive disorder, and Rett syndrome.
This press release and further information about ACADIA can be
found at: www.acadia-pharm.com.
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
pimavanserin as a potential treatment for the hallucinations and
delusions associated with dementia-related psychosis and other
statements that are not historical facts. 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, and 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, 2019 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)
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.
References
1Plassman BL, et al. Prevalence of dementia in the United
States: the Aging Demographics, and Memory study.
Neuroepidemiology. 2007;29(1-2):125-132. 22017 Alzheimer’s Disease
Facts and Figures and ACADIA market research. 3Dementia. (2019,
September 19). Retrieved from
https://www.who.int/news-room/fact-sheets/detail/dementia. 4Connors
MH et al. Am J Geriatr Psychiatry 2018;26(3). Peters ME et al. Am J
Psychiatry 2015;172(5). Haupt M et al. Int J Geriatr Psychiatry
1996;11(11). Naimark D et al. J Am Geriatr Soc 1996;44(3). Stern Y
et al. Neurology 1994;44(12).
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200615005140/en/
Media Contact: ACADIA Pharmaceuticals Inc. Stephanie Fagan (858)
212-0534 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