ACADIA Announces Pimavanserin Meets Primary and Key Secondary Endpoints in Pivotal Phase III Parkinson’s Disease Psychosis

  ACADIA Announces Pimavanserin Meets Primary and Key Secondary Endpoints in
  Pivotal Phase III Parkinson’s Disease Psychosis Trial

   Pimavanserin Demonstrates Highly Significant Antipsychotic Efficacy and
             Maintenance of Motor Control in Parkinson’s Patients

   Significant Improvements Also Observed in All Secondary and Exploratory
                                   Measures

 Conference Call and Webcast to Be Held Today, November 27, 2012, at 8:00 am
                                 Eastern Time

Business Wire

SAN DIEGO -- November 27, 2012

ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD) today announced successful top-line
results from its pivotal Phase III trial evaluating the efficacy, tolerability
and safety of pimavanserin in patients with Parkinson’s disease psychosis
(PDP). Pimavanserin is ACADIA’s proprietary, non-dopaminergic product
candidate that selectively blocks serotonin 5-HT[2A] receptors. Pimavanserin
met the primary endpoint in the Phase III trial by demonstrating highly
significant antipsychotic efficacy as measured using the 9-item SAPS-PD scale
(p=0.001). Pimavanserin also met the key secondary endpoint for motoric
tolerability as measured using Parts II and III of the Unified Parkinson’s
Disease Rating Scale, or UPDRS. These results were further supported by a
highly significant improvement in the secondary efficacy measure, the Clinical
Global Impression Improvement, or CGI-I, scale (p=0.001). In addition,
clinical benefits were observed in all exploratory efficacy measures with
significant improvements in nighttime sleep, daytime wakefulness and caregiver
burden. Consistent with previous studies, pimavanserin was safe and well
tolerated in this Phase III trial.

“These data represent an unprecedented advance for Parkinson’s patients who
suffer from the psychosis frequently associated with this disease,” said
Jeffrey Cummings, M.D., Sc.D., Director of the Cleveland Clinic Lou Ruvo
Center for Brain Health. “Among Parkinson’s patients, psychosis is the leading
cause of institutionalization and dramatically increases the risk of
mortality. Neurologists have limited options to treat this serious disorder,
and off-label use of current antipsychotics is linked to increased risk of
death and serious adverse events, as well as loss of motor control. The
results of this study suggest that a selective, non-dopaminergic-based therapy
has the potential to transform the treatment landscape for patients with this
debilitating disorder.”

Primary Endpoint

The primary endpoint of the trial was antipsychotic efficacy as measured using
the SAPS-PD, a 9-item scale adapted from the hallucinations and delusions
domains of the Scale for the Assessment of Positive Symptoms, by comparing the
mean change from baseline to day 43 for pimavanserin versus placebo. SAPS-PD
assessments were performed by blinded, independent centralized raters. The
pimavanserin arm demonstrated a robust 5.79 point improvement in psychosis at
day 43 compared to a 2.73 point improvement for placebo, representing a highly
significant and clinically meaningful treatment difference of 3.06 points on
SAPS-PD (p=0.001).

                                                             
           Baseline Mean             Mean Change at Day      
                                              43
                PBO        PIM            PBO       PIM           P-value
           (n=90)     (n=95)                       
SAPS-PD     14.73      15.88      -2.73     -5.79     0.001


Note: mixed model repeated measures (MMRM) method was applied in the primary
analysis of the intent-to-treat (ITT) population. The significance test was
based on least-square mean change from baseline for each arm using a 2-sided
beta = 0.05.

Key Secondary Endpoint

The key secondary endpoint of the trial evaluated motoric tolerability and
functional outcome using Parts II and III of the UPDRS. The objective of this
secondary endpoint was to demonstrate that pimavanserin could achieve its
antipsychotic effects without worsening motor function as compared to placebo
in PDP patients. A pre-specified, non-inferiority analysis was used to compare
the mean change from baseline to day 43 for pimavanserin versus placebo using
a two-sided 95 percent confidence interval (CI) for the treatment difference.
Motoric improvements were seen in both the pimavanserin and placebo arms and
the CI associated with the treatment difference did not exceed a pre-specified
margin of 5 points for clinically relevant change, confirming that
pimavanserin met this key secondary endpoint and did not worsen motor function
in PDP patients.

Secondary and Exploratory Efficacy Measures

The secondary efficacy measure in the trial was an assessment of clinical
global improvement by the investigator using the CGI-I scale. Pimavanserin
demonstrated a highly significant improvement on this measure (p=0.001),
further supporting its antipsychotic efficacy.

In addition, other clinical benefits of pimavanserin were observed in
exploratory efficacy measures of sleep and caregiver burden. Sleep was
assessed using the SCOPA-sleep scale, which was designed to enable the
investigator to evaluate nighttime sleep and daytime wakefulness in
Parkinson’s patients. Pimavanserin demonstrated significant improvements on
both nighttime sleep (p=0.045) and daytime wakefulness (p=0.012) on SCOPA.

Caregiver burden was assessed using the Caregiver Burden Scale. This scale was
completed by the caregiver to provide a quantitative assessment of burden
associated with the patient’s functional/behavioral impairments, the
circumstances of at-home care, as well as the caregiver’s health, social life
and interpersonal relations. Pimavanserin demonstrated a highly significant
improvement on the Caregiver Burden Scale (p=0.002).

Safety and Tolerability Profile

Consistent with previous studies, pimavanserin was safe and well tolerated in
this trial. Based on a preliminary analysis of safety data, the most common
adverse events were urinary tract infection (11.7% PBO vs. 13.5% PIM) and
falls (8.5% PBO vs. 10.6% PIM). Adverse events were generally characterized as
mild to moderate in nature. The only serious adverse events that occurred in
more than one patient were urinary tract infection (1-PBO vs. 3-PIM) and
psychotic disorder (0-PBO vs. 2-PIM). Ninety percent of the patients who
completed the clinical phase of this trial elected to roll over into the
ongoing open-label safety extension study. Patients were only eligible to
participate in the extension study if the treating investigator also deemed
them to be likely to benefit from continued treatment with pimavanserin.

“We are excited with the results of this study which demonstrate that
pimavanserin has the potential to offer PDP patients a new treatment option
that, for the first time, can achieve the desired clinical profile by
providing an effective, safe and well tolerated antipsychotic therapy,” said
Uli Hacksell, Ph.D., Chief Executive Officer of ACADIA. “We remain committed
to advancing pimavanserin to registration as a first-in-class treatment for
this large unmet medical need. These results also suggest that pimavanserin
may have the ideal clinical profile to address a broader range of
neuropsychiatric disorders that are underserved by currently marketed
antipsychotics.”

“These significant and consistent top-line results are a strong validation of
the optimized study design used in this trial,” said Roger G. Mills, M.D.,
ACADIA’s Executive Vice President of Development. “Encouragingly, benefits of
pimavanserin were seen by patients, caregivers and investigators, as well as
the independent raters. Following the successful outcome of this pivotal Phase
III trial, we will continue our ongoing preparations for a confirmatory
pivotal Phase III trial, the -021 Study, using the same trial design.”

About the Trial Design

The pivotal Phase III trial, referred to as the -020 Study, was a
multi-center, double-blind, placebo-controlled study designed to evaluate the
efficacy, tolerability and safety of pimavanserin as a treatment for patients
with PDP. A total of 199 patients were enrolled in the study and randomized on
a one-to-one basis to receive either 40 mg of pimavanserin or placebo
once-daily for six weeks, following a two-week screening period including
brief psycho-social therapy. Patients also received stable doses of their
existing anti-Parkinson’s therapy throughout the study. The primary endpoint
of the -020 Study was antipsychotic efficacy as measured using the “SAPS–PD”
scale, which consists of nine items from the hallucinations and delusions
domains of the Scale for the Assessment of Positive Symptoms, or SAPS. These
nine items have been shown to be particularly relevant to the expression of
psychotic symptoms in patients with Parkinson’s disease and to have high
inter-rater reliability for assessment of severity. Motoric tolerability was a
key secondary endpoint in the study and was measured using Parts II and III of
the Unified Parkinson’s Disease Rating Scale, or UPDRS.

Conference Call and Webcast Information

ACADIA will host a conference call and webcast with slides today, November 27,
2012 at 8:00 a.m. Eastern Time to present the top-line results from its
pivotal Phase III trial with pimavanserin in patients with PDP. The conference
call can be accessed by dialing 866-783-2140 for participants in the U.S. and
Canada and 857-350-1599 for international callers (reference passcode
26249437). The conference call will be webcast live on ACADIA’s website,
www.acadia-pharm.com, under the investors section and will be archived there
until December 11, 2012. A telephone replay also may be accessed through
December 11, 2012 by dialing 888-286-8010 for participants in the U.S. and
Canada and 617-801-6888 for international callers (reference passcode
47904115).

About Pimavanserin

Pimavanserin is ACADIA’s proprietary small molecule that acts selectively as
an antagonist/inverse agonist on serotonin 5-HT[2A] receptors and is in Phase
III development as a potential first-in-class treatment for Parkinson’s
disease psychosis. Pimavanserin can be taken orally as a tablet once-a-day.
ACADIA discovered pimavanserin and holds worldwide rights to this new chemical
entity.

About Parkinson’s Disease Psychosis

According to the National Parkinson’s Foundation, about one million people in
the United States and from four to six million people worldwide suffer from
Parkinson’s disease. Parkinson’s disease psychosis, or PDP, is a debilitating
disorder that develops in up to 60 percent of patients with Parkinson’s
disease. Currently, there is no FDA-approved therapy to treat PDP in the
United States. PDP, commonly consisting of visual hallucinations and
delusions, substantially contributes to the burden of Parkinson’s disease and
deeply affects the quality of life of patients. PDP is associated with
increased caregiver stress and burden, nursing home placement, and increased
morbidity and mortality. There is a large unmet medical need for new therapies
that will effectively treat PDP without compromising motor control in patients
with Parkinson’s disease.

About ACADIA Pharmaceuticals

ACADIA is a biopharmaceutical company focused on innovative treatments that
address unmet medical needs in neurological and related central nervous system
disorders. ACADIA has a pipeline of product candidates led by pimavanserin,
which is in Phase III development as a potential first-in-class treatment for
Parkinson's disease psychosis. ACADIA also has clinical-stage programs for
chronic pain and glaucoma in collaboration with Allergan, Inc. and two
advanced preclinical programs directed at Parkinson’s disease and other
neurological disorders. All product candidates are small molecules that
emanate from discoveries made at ACADIA. ACADIA maintains a website at
www.acadia-pharm.com to which ACADIA regularly posts copies of its press
releases as well as additional information and through which interested
parties can subscribe to receive email alerts.

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 the progress and timing of ACADIA’s drug discovery
and development programs, either alone or with a partner, including the
commencement or progress of clinical trials and the results of clinical
trials, and the clinical benefits to be derived from ACADIA’s product
candidates, in each case including pimavanserin. In particular,
forward-looking statements include statements regarding the potential
implications of the results of the -020 study; the potential for selective,
non-dopaminergic-based therapy, such as pimavanserin, to transform the
treatment landscape for patients with PDP; the potential of pimavanserin as a
first-in-class, effective, safe and well tolerated antipsychotic therapy and
treatment for PDP; and the possibility that pimavanserin may have a clinical
profile suitable to address a broader range of neuropsychiatric disorders that
are underserved by currently marketed antipsychotics. 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, regulatory review and commercialization, and in collaborations
with others, 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 December31, 2011 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.

Contact:

Investor Contacts:
ACADIA Pharmaceuticals Inc.
Uli Hacksell, Ph.D., Chief Executive Officer
Thomas H. Aasen, Executive Vice President,
Chief Financial Officer and Chief Business Officer
(858) 558-2871
or
Media Contact:
Russo Partners
David Schull
(212) 845-4271 or (858) 717-2310
david.schull@russopartnersllc.com
 
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