- Pimavanserin met primary endpoint with statistically significant
overall improvement in HAMD-17 total score compared to placebo (p=0.039)
- Pimavanserin met key secondary endpoint with statistically
significant overall improvement in Sheehan Disability Scale compared to
- Positive results also observed on seven additional secondary
endpoints including responder rate, improvement in sexual function, and
reduction in daytime sleepiness
- ACADIA to initiate Phase 3 program in adjunctive MDD in 1H 2019
- Conference call and webcast to be held today at 8:30 a.m. Eastern
SAN DIEGO--(BUSINESS WIRE)--Oct. 31, 2018--
ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD) today announced positive
top-line results from CLARITY, a randomized, double-blind,
placebo-controlled, multi-center, sequential parallel comparison design
(SPCD) study in major depressive disorder (MDD). In the study, 207 adult
patients with a confirmed inadequate response to existing first-line
SSRI or SNRI therapy for MDD received adjunctive treatment of either 34
mg pimavanserin or placebo in addition to pre-existing first-line
therapy for five weeks (Stage 1). Those patients who did not show a
response to placebo in Stage 1 were re-randomized to receive either
pimavanserin or placebo for a second five-week treatment period (Stage
In the trial, pimavanserin met the overall primary endpoint of the
weighted average results of Stage 1 and Stage 2 by significantly
reducing 17-item Hamilton Depression Rating Scale (HAMD-17) total score
compared to placebo (p=0.039). In addition, in Stage 1 (n=207) patients
on pimavanserin demonstrated a highly significant improvement in HAMD-17
(p=0.0003). Importantly, this group of patients saw a benefit over
placebo in the first week of treatment (p=0.0365). Stage 2 (n=58)
results did not demonstrate significant separation in this small set of
On the key secondary endpoint, pimavanserin demonstrated statistically
significant reductions compared to placebo in the Sheehan Disability
Scale (SDS) score (p=0.004).
Positive results were also observed for seven of the eleven other
secondary endpoints listed below with nominal p-values: Clinical Global
Impression-Severity (p=0.0084), Clinical Global Impression-Improvement
(p=0.0289), Short Form-12 Mental Component Summary (p<0.0001),
Karolinska Sleepiness Scale (p=0.0205), Massachusetts General Hospital
Sexual Functioning Index (p=0.0003), Barratt Impulsiveness Scale
(p=0.0075), as well as response rates (p=0.0065), defined as a 50% or
greater reduction on the HAMD-17 total score.
In this Phase 2 study, pimavanserin was generally well-tolerated.
Discontinuations due to adverse events were 1.2% for pimavanserin and
3.2% for placebo. One subject in each of the pimavanserin and placebo
groups reported serious adverse events (SAEs). These SAEs were deemed
not to be related to the study drug by the investigators and both
subjects completed the study. No deaths were reported in the study.
“We are pleased with the robustness of the data from our Phase 2 CLARITY
trial, which shows significant promise for patients with MDD, including
early and sustained antidepressant response over placebo, decreased
daytime sleepiness, no meaningful weight gain, and improved sexual
function. This is important because most people with MDD do not respond
to initial antidepressant therapies and experience significant unwanted
side effects,” said Serge Stankovic, M.D., M.S.P.H., ACADIA's Executive
Vice President, Head of Research & Development. “Pimavanserin is a
selective serotonin inverse agonist, or SSIA, that shows great potential
as an antidepressant. We look forward to engaging with the FDA and
initiating a Phase 3 program in the first half of 2019.”
“The results of this study suggest pimavanserin may represent a novel
approach to adjunctive treatment for patients suffering from major
depressive disorder. The selective serotonergic mechanism of action may
provide additional benefit for patients who do not adequately respond to
SSRI or SNRI treatment,” said Professor Maurizio Fava, M.D., Executive
Vice Chair, Department of Psychiatry, Massachusetts General Hospital
(MGH) and Associate Dean for Clinical & Translational Research, Harvard
Medical School. “The majority of patients with MDD do not respond
adequately to initial antidepressant therapy and the treatment effect
seen in this study combined with a favorable tolerability profile
provides evidence that adjunctive therapy with pimavanserin may benefit
patients suffering from inadequate response in major depressive
CLARITY was a Phase 2, 10-week, randomized,
double-blind, placebo-controlled, multi-center, 2-stage sequential
parallel comparison design (SPCD) study that evaluated the safety,
tolerability, and efficacy of pimavanserin (34 mg once daily) 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 was conducted in
collaboration with the MGH Clinical Trials Network & Institute (CTNI)
and randomized 207 patients across 28 clinical research centers in the
Consistent with the SPCD design, the study was conducted in two,
five-week sequential stages. Eligible subjects continued receiving their
SSRI or SNRI antidepressant at a stable dose for the duration of the
study. Patients were randomly assigned (1:3) to pimavanserin 34 mg/day
or placebo in Stage 1. Placebo non-responders in Stage 1 (defined as
HAMD-17 total score >14 and a percent-reduction from baseline in HAMD-17
total score of <50% at week 5) were re-randomized (1:1) to Stage 2 to
receive pimavanserin 34 mg/day or placebo. The primary endpoint of the
study was the change in HAMD-17 total score for Stage 1 and Stage 2.
Treatment differences from Stage 1 and Stage 2 were combined as weighted
A post-hoc comparison between pimavanserin (n=51) and placebo (n=123)
for patients consistently receiving either placebo or pimavanserin for
the entire 10-week period also yielded meaningful separation with
positive p-values at all weeks starting from week 2 to week 10 in favor
of pimavanserin for both the primary endpoint, HAMD-17 (week 10,
p=0.0076), and the key secondary endpoint, SDS (week 10, p=0.0094).
Conference Call and Webcast Information
ACADIA will discuss
top-line results from its Phase 2 trial of pimavanserin for adjunctive
treatment of patients with major depressive disorder via conference call
and webcast today at 8:30 a.m. Eastern Time. The conference call can be
accessed by dialing 855-638-4820 for participants in the U.S. or Canada
and 443-877-4067 for international callers (reference passcode 8786247).
A telephone replay of the conference call may be accessed through
November 30, 2018 by dialing 855-859-2056 for callers in the U.S. or
Canada and 404-537-3406 for international callers (reference passcode
8786247). The conference call will also be webcast live on ACADIA’s
in the investors section and archived until November 30, 2018.
About Major Depressive Disorder (MDD)
According to the
National Institute of Mental Health, MDD affects approximately 16
million adults in the United States1, with approximately 2.5
million adults treated with adjunctive therapy2,3. 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 therapy4.
Pimavanserin is a selective serotonin
inverse agonist (SSIA) 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 major depressive disorder.
Pimavanserin (34 mg) 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
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 is commercializing the first and
only medicine approved for the treatment of hallucinations and delusions
associated with Parkinson’s disease psychosis. In addition, ACADIA 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 discovery, 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, 2017 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.
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).
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Source: ACADIA Pharmaceuticals Inc.
ACADIA Pharmaceuticals Inc.
ACADIA Pharmaceuticals Inc.