- Pimavanserin met the primary endpoint in the
study, significantly reducing the risk of relapse of psychosis by
2.8 fold (Hazard Ratio (HR)=0.353, one-sided p=0.0023)
- Pimavanserin met the key secondary endpoint
in the study, significantly reducing the risk of discontinuation
for any reason by 2.2 fold (HR=0.452, one-sided p=0.0024)
- Currently, there is no FDA-approved drug for
the treatment of dementia-related psychosis
- Webcast to be held today at 7:15 p.m. Pacific
Time
ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD) today presented
positive top-line results from its Phase 3 HARMONY study at the
12th Clinical Trials on Alzheimer’s Disease (CTAD) Meeting,
December 4 -7, 2019 in San Diego, California. HARMONY was a
double-blind, placebo-controlled, relapse prevention study in 392
patients evaluating pimavanserin for the treatment of
dementia-related psychosis.
Pimavanserin met the primary endpoint of the study and was
stopped at the pre-planned interim analysis by significantly
reducing risk of relapse of psychosis by 2.8 fold compared to
placebo (HR = 0.353; one-sided p=0.0023). In addition, pimavanserin
met the key secondary endpoint by significantly reducing risk of
discontinuation for any reason by 2.2 fold (HR = 0.452; one-sided
p=0.0024).
“The results presented today are an important advance for
patients and caregivers who struggle with the burden of
dementia-related psychosis where no FDA-approved treatment is
currently available,” said Jeffrey Cummings, M.D., Sc.D., Director
Emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health in
Las Vegas. “Reducing the risk of relapse of psychotic symptoms by
this magnitude is an important and meaningful outcome as these are
serious events which could lead to poor patient outcomes and a
significant increase in caregiver burden and distress.”
The Phase 3 HARMONY study included a 12-week open-label
pimavanserin treatment period prior to the randomization period of
the study. In this open-label treatment period, 61.8% of eligible
patients met pre-specified criteria for pimavanserin treatment
response at both week 8 and week 12 and were subsequently
randomized into the double-blind period of the study. For patients
in the open-label treatment period, change from baseline to week 8
and week 12 on the Scale for the Assessment of Positive
Symptoms-Hallucinations and Delusions (SAPS-H+D) score improved by
63.0% and 75.2% respectively.
“We are extremely pleased to announce the top-line results from
this landmark Phase 3 study in dementia-related psychosis,” said
Serge Stankovic, M.D., M.S.P.H., ACADIA's President. “The HARMONY
study was designed to answer three very important questions. First,
in the 12-week open-label period, pimavanserin treatment showed a
meaningful reduction of the symptoms and stabilization of psychosis
across all of the five clinically diagnosed subtypes evaluated.
Second, in the 26-week double-blind period, patients on
pimavanserin had a nearly three-fold reduction of risk of relapse
compared to patients on placebo. And third, pimavanserin was
well-tolerated by elderly patients with dementia-related psychosis.
We look forward to discussing these results with the FDA in the
first half of 2020.”
Pimavanserin was well-tolerated over the entire 9-month study
duration. Patients receiving pimavanserin treatment had no
worsening in cognition, as measured by the Mini-Mental State
Examination (MMSE) score, from baseline and no worsening of motor
symptoms, as measured by the Extrapyramidal Symptom Rating Scale
A-score (ESRS-A), from baseline. In the double-blind period, low
rates of adverse events were observed, 41.0% of patients on
pimavanserin and 36.6% on placebo. Discontinuations due to adverse
events were low, 2.9% for pimavanserin and 3.6% for placebo.
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. Additionally,
pimavanserin did not result in clinically significant differences
in vital signs, weight, or daytime sedation compared to
placebo.
ACADIA is planning to meet with the FDA in the first half of
2020 regarding a supplemental NDA submission. The FDA previously
granted Breakthrough Therapy Designation for pimavanserin for the
treatment of dementia-related psychosis. Currently, no drug is
approved by the FDA for the treatment of dementia-related
psychosis.
About the HARMONY Study
HARMONY was a Phase 3 study designed to evaluate the efficacy
and safety of pimavanserin for the treatment of delusions and
hallucinations 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 HARMONY study. The
average age of patients in the study was 74.5 years. Patients had
an average baseline SAPS-H+D score of 24.4, which is reflective of
moderate-to-severe psychosis and an average baseline MMSE score of
16.7, which is consistent with the greatest proportion of enrolled
patients having moderate dementia.
The HARMONY study included a 12-week open-label stabilization
period during which patients with dementia-related psychosis were
treated with pimavanserin 34 mg once daily. Dose reduction to 20 mg
once daily was allowed based on tolerability within the first four
weeks. Following the 12-week 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. 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. Pimavanserin met the primary endpoint of the
study by significantly reducing the risk of relapse of psychosis by
2.8 fold compared to placebo (HR = 0.353; one-sided p=0.0023).
Relapse (psychotic exacerbation or significant worsening of
dementia-related psychosis after prior stabilization) was defined
in the study by one or more of the following: hospitalization due
to dementia-related psychosis, significant worsening of
dementia-related psychosis as measured by clinical scales and
investigator impression, withdrawal from the study due to lack of
efficacy, or the use of an off-label antipsychotic medication for
the treatment of dementia-related delusions and/or hallucinations.
All potential relapses and discontinuations in the double-blind
portion of the study were adjudicated by an independent
adjudication committee to determine if protocol defined relapse
criteria were met.
Webcast Information
The live webcast will include a presentation of the results by
ACADIA management followed by a KOL panel discussion and will begin
at 7:15 p.m. Pacific Time. The live webcast will be available on
ACADIA’s website, www.acadia-pharm.com, under the investors section
and will be archived there through January 4, 2020.
About Dementia-Related Psychosis
Around 8 million people in the United States are living with
dementia and studies suggest that approximately 30% of dementia
patients, or 2.4 million people, have psychosis, commonly
consisting of delusions and hallucinations1,2. Dementia-related
psychosis includes psychosis in Alzheimer’s disease, dementia with
Lewy bodies, Parkinson’s disease dementia, vascular dementia, and
frontotemporal dementia. Serious consequences have been associated
with severe or persistent psychosis in patients with dementia such
as repeated hospital admissions, increased likelihood of nursing
home placement, progression of dementia, and increased risk of
morbidity and mortality3.
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 across multiple indications with
significant unmet need including dementia-related psychosis,
adjunctive major depressive disorder, and the 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, major depressive
disorder, the negative symptoms of schizophrenia, 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
expected timelines with respect to the Company’s planned engagement
with the FDA. 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, 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, 2018 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)
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.
- 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 most 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.
Indication: NUPLAZID is indicated for the treatment of
hallucinations and delusions associated with Parkinson’s disease
psychosis.
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 see the full Prescribing Information including Boxed
WARNING for NUPLAZID.
References
12017 Alzheimer’s Disease Facts and Figures and ACADIA market
research 2Plassman BL, et al. Prevalence of dementia in the United
States: the Aging Demographics, and Memory study.
Neuroepidemiology. 2007;29(1-2):125-132. 3Connors 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/20191204005956/en/
Investor Contact: ACADIA Pharmaceuticals Inc. Mark Johnson, CFA
(858) 261-2771 ir@acadia-pharm.com
Media Contact: ACADIA Pharmaceuticals Inc. Maurissa Messier
(858) 768-6068 media@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