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-HT2A 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-HT2A
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 December 31, 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.
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