- Pimavanserin met the primary endpoint of
reduced risk of relapse of psychosis by 2.8 fold compared to
placebo
- Pimavanserin met the secondary endpoint of
significantly reducing trial discontinuation for any reason by 2.2
fold
Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) announced today that
the New England Journal of Medicine published results from the
Phase 3 HARMONY study, an international, double-blind,
placebo-controlled relapse prevention trial in 392 patients
evaluating pimavanserin as an investigational treatment in patients
with hallucinations and delusions associated with dementia-related
psychosis (DRP). The study included patients across five subgroups
of dementia: Alzheimer’s disease, dementia with Lewy bodies,
frontotemporal dementia, Parkinson’s disease dementia, and vascular
dementia.
The HARMONY study was stopped early due to positive efficacy at
the pre-planned interim analysis upon recommendation of the trial’s
independent data safety monitoring board. HARMONY met its primary
endpoint by significantly reducing the risk of relapse of psychosis
by 2.8 fold compared to placebo in the double-blind period (hazard
ratio (HR)=0.35, two-sided p=0.005; one-sided p=0.0023). The study
also met its secondary endpoint by significantly reducing the time
to trial discontinuation for any reason (HR=0.45, two-sided
p=0.005; one-sided p=0.0024). The data from the HARMONY study
demonstrates that patients with DRP who had responded to
pimavanserin had a significantly lower risk of relapse of psychosis
with continuation of pimavanserin compared to placebo up to 26
weeks.
“The relapse prevention design of the HARMONY study mirrors
exactly what we do in clinical practice. This landmark trial showed
that when patients responded to pimavanserin and then continued
treatment, they were almost three times less likely to develop
recurrence of their hallucinations and delusions than those
patients who discontinued pimavanserin treatment,” said the study’s
lead author, Dr. Pierre N. Tariot, Banner Alzheimer’s Institute
director. “This is a substantial finding and a significant advance
for a critical public health need in our field. There is no FDA
approved treatment for DRP, and the majority of antipsychotics
currently used off-label have equivocal efficacy and may accelerate
cognitive decline.”
Pimavanserin was well-tolerated over the nine-month study
duration. In a pre-specified analysis, pimavanserin was not
associated with a decline in cognition as measured by Mini-Mental
State Examination (MMSE) or the onset or worsening of motor
symptoms as measured by Extrapyramidal Symptom Rating Scale A
(ESRS-A).
“The HARMONY study findings demonstrated three important
results. First, in the 12-week open-label period, pimavanserin
treatment showed a sustained reduction of psychotic symptoms.
Second, in the 26-week double-blind period, patients on
pimavanserin had a nearly three-fold reduction of risk of psychosis
relapse compared to patients on placebo. Third, pimavanserin was
well-tolerated by elderly patients with DRP,” said Steve Davis,
Chief Executive Officer of Acadia. “We are very pleased that the
New England Journal of Medicine has chosen to publish the important
results of this study.”
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. The study
included patients with Alzheimer’s disease, dementia with Lewy
bodies, frontotemporal dementia, Parkinson’s disease dementia, and
vascular dementia. A total of 392 patients were enrolled in the
study, with a mean age of 74.5 years and a mean MMSE score of 16.7.
The primary endpoint in the study was time from randomization to
relapse of psychosis in the double-blind period as represented by
the Kaplan-Meier curve and the hazard ratio.
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 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 sustained treatment
response were then randomized into the double-blind period of the
study to continue their pimavanserin dose 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 (HR=0.35,
p=0.005).
In the double-blind period, similar, low rates of adverse events
were observed, 43 (41.0%) patients on pimavanserin (n=105) and 41
(36.6%) patients on placebo (n=112). 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 that 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.1 In addition to cognitive decline,
dementing illnesses almost universally lead to neuropsychiatric
symptoms, which may include 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
delusions.2,3 These symptoms may be frequent and severe and may
recur over time. 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. A delusion is
defined as a false, fixed belief that is resolutely held despite
evidence to the contrary. 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
mortality.4
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 dementia-related psychosis. In
addition, Acadia is developing pimavanserin in other
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.
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.
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 1Dementia. (2019, September 19). Retrieved from
https://www.who.int/news-room/fact-sheets/detail/dementia.
2Plassman BL, et al. Prevalence of dementia in the United States:
The Aging Demographics, and Memory study. Neuroepidemiology.
2007;29(1-2):125-132. 32017 Alzheimer’s Disease Facts and Figures
and Acadia market research. 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).
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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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