ACADIA Pharmaceuticals Announces Publication in The Lancet of Pivotal Phase III Parkinson's Disease Psychosis Trial with Pimavanserin
SAN DIEGO (Business Wire) -- ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD),
a biopharmaceutical company
focused on innovative treatments that address unmet medical needs in
neurological and related central nervous system disorders, today
announced the publication of data from its pivotal Phase III -020 Study
with pimavanserin in patients with Parkinson's disease psychosis (PDP)
in the November 1, 2013 online issue of The Lancet. In the -020
Study, pimavanserin demonstrated significant and clinically meaningful
benefits and was safe and well tolerated in patients with PDP.
Pimavanserin significantly reduced psychosis and maintained motor
control in patients with PDP. Significant benefits were also observed in
exploratory measures of nighttime sleep, daytime wakefulness and
caregiver burden.
"Among Parkinson's patients, psychosis causes great distress for
patients and caregivers and is the leading cause of
institutionalization," said Jeffrey Cummings, M.D., Sc.D., Director of
Cleveland Clinic Lou Ruvo Center for Brain Health, and lead author.
"These data indicate that pimavanserin, a selective 5-HT2A inverse
agonist, confers a meaningful clinical benefit in patients with PDP and
has the potential to be an important new treatment option for this
condition for which there is no approved therapy in the U.S."
Pimavanserin met the primary endpoint in the -020 Study by demonstrating
highly significant improvement in psychosis compared to placebo on the
9-item SAPS-PD scale (p=0.001), which was assessed by central,
independent raters. The mean change in SAPS-PD score represented a 37%
improvement for pimavanserin versus 14% for placebo (p<0.001).
Pimavanserin also demonstrated significant improvement on the full
20-item SAPS (hallucinations plus delusions) measure (p=0.001) and on
each of the separate hallucinations and delusions domains in supportive
analyses.
Significant improvements were observed for pimavanserin over placebo on
additional investigator-assessed secondary measures of psychosis
benefit, including the Clinical Global Impression Severity, or CGI-S,
scale (p<0.001), and the Clinical Global Impression Improvement, or
CGI-I, scale (p=0.001). The proportion of CGI-I responders was also
higher for pimavanserin versus placebo, (49% vs. 26%, p=0.002).
Pimavanserin 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. Caregivers in the pimavanserin group also
reported significant reduction in caregiver burden (p=0.002), and
participants reported significant improvements on nighttime sleep
(p=0.045) and daytime wakefulness (p=0.012) for pimavanserin over
placebo in exploratory analyses.
Consistent with previous studies, pimavanserin was well tolerated in the
-020 Study with no significant safety concerns or impairment in motor
function. The most common treatment-emergent adverse events were urinary
tract infection (13.5% PIM vs. 11.7% PBO) and falls (10.6% PIM vs. 8.5%
PBO). Although adverse event discontinuations were higher in the
pimavanserin group compared to placebo, overall drop-outs in the -020
Study were low compared to other reported studies in PDP and similar
neuropsychiatric conditions.
"The -020 Study results presented in The Lancet suggest that
pimavanserin has the potential to provide a safe, well-tolerated, and
effective alternative to existing antipsychotic drugs. Current atypical
antipsychotics are often used off-label to treat PDP despite increasing
evidence that they are associated with serious safety issues and are
poorly tolerated in this fragile and elderly patient population," said
Clive Ballard, M.D., Professor of Age Related Diseases at King's College
London.
Phase III -020 Study 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 Parkinson's disease psychosis. 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 (SAPS). Additional secondary and supportive measures
of efficacy were measured using the Clinical Global Impression Severity
(CGI-S) scale, the Clinical Global Impression Improvement (CGI-I) scale,
and the full 20-item SAPS. Exploratory measures of nighttime sleep,
daytime wakefulness, and caregiver burden were measured using the Scales
for Outcome in Parkinson's Disease - Nighttime Sleep (SCOPA-NS), the
Scales for Outcome in Parkinson's Disease - Daytime Sleep (SCOPA-DS),
and the Caregiver Burden Scale (CBS), respectively. 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 (UPDRS).
About Pimavanserin
Pimavanserin is ACADIA's proprietary small molecule that acts
selectively as an antagonist/inverse agonist on serotonin 5-HT2A receptors.
ACADIA has successfully completed a pivotal Phase III trial with
pimavanserin for Parkinson's disease psychosis (PDP), potentially
positioning it to be the first drug approved in the United States for
the treatment of this disorder. Pimavanserin is also in Phase II
development for Alzheimer's disease psychosis (ADP) and has completed a
Phase II trial as a co-therapy in schizophrenia. Pimavanserin is
formulated as a tablet and is administered orally 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.
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