SAN DIEGO–(BUSINESS WIRE)–ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD), a biopharmaceutical company
focused on the development and commercialization of innovative medicines
to address unmet medical needs in central nervous system disorders,
today announced it will present data from its Phase 2 CLARITY study,
which evaluated the efficacy, safety, and tolerability of pimavanserin
as an adjunctive treatment for major depressive disorder (MDD) at the
2019 American Psychiatric Association Annual Meeting in San Francisco,
May 18 – 22, 2019.
Date/Time: Tuesday, May 21, 2:00 p.m. – 4:00 p.m. Pacific
Title: CLARITY: A Phase 2 Double-blind, Placebo-controlled
Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in
Major Depressive Disorder
The Phase 2 CLARITY study was a 10-week, randomized, double-blind,
placebo-controlled, multi-center, two-stage sequential parallel
comparison design study that evaluated the efficacy, safety, and
tolerability of pimavanserin (34 mg once daily). Pimavanserin was
administered as an adjunctive treatment in patients with MDD who had an
inadequate response to a stable dose of standard antidepressant therapy
with either a selective serotonin reuptake inhibitor (SSRI) or a
serotonin norepinephrine reuptake inhibitor (SNRI). The study randomized
207 patients across 27 clinical research centers in the U.S. and was
conducted in collaboration with the Massachusetts General Hospital (MGH)
Clinical Trials Network and Institute.
“There is a significant need for new therapies for the majority of
patients suffering from major depressive disorder who do not respond to
initial antidepressant therapy,” said Professor Maurizio Fava, M.D.,
Executive Vice Chair, Department of Psychiatry, MGH, Director of the
Division of Clinical Research of the MGH Research Institute, and
Associate Dean for Clinical & Translational Research, Harvard Medical
School. “The results observed in the Phase 2 CLARITY study combined with
a favorable tolerability profile provides evidence that adjunctive
treatment with pimavanserin may provide meaningful benefit to those MDD
patients who have an inadequate response to either a SSRI or a SNRI
In the trial, pimavanserin met the overall primary endpoint of the
weighted average results of Stage 1 and Stage 2 by significantly
reducing the 17-item Hamilton Depression Rating Scale total score
compared to placebo (p=0.039). On the key secondary endpoint,
pimavanserin demonstrated statistically significant reductions compared
to placebo in the Sheehan Disability Scale score (p=0.004). Positive
results were also observed for seven other secondary endpoints,
including improvement in daytime sleepiness as measured by the
Karolinska Sleepiness Scale and improvement in sexual function as
measured by the Massachusetts General Hospital Sexual Functioning Index.
“In this Phase 2 study of pimavanserin as an adjunctive treatment for
MDD, we found patients treated with pimavanserin experienced significant
reduction in their depression symptoms in addition to improvement in
daytime sleepiness and sexual function when compared to placebo,” said
Serge Stankovic, M.D., M.S.P.H., ACADIA’s President. “These results are
encouraging for patients with MDD who may experience challenges with
their current treatment options. We look forward to further evaluating
pimavanserin as an adjunctive treatment in our ongoing Phase 3 CLARITY
On April 25, ACADIA
announced it had initiated its Phase 3 CLARITY program for
pimavanserin as an adjunctive treatment for MDD. The CLARITY-2 study
will be based in the U.S. and has already initiated enrollment and the
CLARITY-3 study will be based outside the U.S. and will initiate
enrollment in the upcoming months. Both studies are six-week,
parallel-designed, randomized, double-blind, placebo-controlled,
multi-center studies designed to evaluate the efficacy and safety of
pimavanserin as adjunctive treatment in patients with MDD who have an
inadequate response to standard antidepressant therapy with either a
SSRI or a SNRI.
About Major Depressive Disorder
According to the National
Institute of Mental Health, MDD affects approximately 16 million adults
in the U.S.1, with approximately 2.5 million adults treated
with adjunctive therapy.2,3 MDD is a condition characterized
by depressive symptoms such as a depressed mood or a loss of interest or
pleasure in daily activities for more than two weeks, as well as
impaired social, occupational, or other important functioning. The
majority of people who suffer from MDD do not respond adequately to
initial antidepressant therapy.4
Pimavanserin is a selective serotonin
inverse agonist and antagonist preferentially targeting 5-HT2A
receptors. These receptors are thought to play an important role in
depression, psychosis, and other neuropsychiatric disorders. ACADIA is
evaluating pimavanserin in an extensive clinical development program
across multiple indications with significant unmet need including
dementia-related psychosis, schizophrenia inadequate response,
schizophrenia-negative symptoms, and MDD. 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 the adjunctive treatment of patients with MDD.
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, schizophrenia inadequate response, schizophrenia-negative
symptoms, major depressive disorder, and Rett syndrome. This press
release and further information about ACADIA can be found at: www.acadia-pharm.com.
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: the potential benefits of pimavanserin as adjunctive
treatment for MDD or other central nervous system disorders as well as
the potential results of clinical trials of pimavanserin in other
indications. 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
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
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
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
- The use of NUPLAZID should be avoided in patients with known QT
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%).
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.
- Coadministration with strong CYP3A4 inhibitors (e.g.,
Indication: NUPLAZID is indicated for the treatment of
hallucinations and delusions associated with Parkinson’s disease
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.
1National Institute of Mental Health.
(2017). Major Depression. Retrieved from http://www.nimh.nih.gov/health/statistics/major-depression.shtml.
2IMS NSP, NPA, NDTI MAT-24 month data through Aug-2017.
3PLOS One, Characterization of Treatment Resistant Depression
Episodes in a Cohort of Patients from a US Commercial Claims
Database, Oct 2013, Vol 8, Issue 10.
4Rush AJ, et al. (2007) Am J. Psychiatry 163:11, pp.
1905-1917 (STAR*D Study).
ACADIA Pharmaceuticals Inc.
ACADIA Pharmaceuticals Inc.