SAN DIEGO, Dec. 1 /PRNewswire-FirstCall/ -- ACADIA Pharmaceuticals Inc.
(Nasdaq: ACAD), a biopharmaceutical company utilizing innovative technology to
fuel drug discovery and clinical development of novel treatments for central
nervous system disorders, today reported results from a Phase II study that
showed that ACP-103 reduced haloperidol-induced akathisia, a debilitating
extrapyramidal side effect, in patients with schizophrenia.
This study is one of two Phase II clinical trials in ACADIA's program
using ACP-103 adjunctively with other antipsychotic drugs to provide an
improved therapy for schizophrenia patients. The study involved 34 patients
with schizophrenia and was designed to evaluate the ability of ACP-103 to
treat akathisia, a side effect often induced by antipsychotic drugs. In
addition to this study, ACADIA is currently conducting a Phase II trial with
up to 400 patients, which is designed to evaluate the ability of ACP-103 to
improve both the efficacy and safety profile of current antipsychotic drugs.
"We are encouraged by the ability of ACP-103 to treat haloperidol-induced
akathisia in patients with schizophrenia," said Uli Hacksell, Ph.D., ACADIA's
Chief Executive Officer. "This study is an important demonstration of our
ACP-103 adjunctive therapy approach to improve the quality of care for
patients suffering from schizophrenia."
Trial Design
The double-blind, randomized, placebo-controlled Phase II study enrolled
34 patients with a clinical diagnosis of schizophrenia or schizoaffective
disorder, who also experienced haloperidol-induced akathisia. Results from
the study presented in the accompanying table are based on 30 patients who
completed the study protocol and exclude 4 subjects who had major protocol
violations. Fourteen of these 30 patients received once-daily oral
administration of 60 mg of ACP-103 and 16 were administered placebo over a
five-day period. Subjects were maintained on their pre-study dose of
haloperidol during the course of the study.
Patients were evaluated using the Barnes Akathisia Scale (BAS), a
four-item rating scale widely used to assess this particular side effect of
antipsychotic drugs. This scale consists of the following items: objective
akathisia (Item 1), subjective awareness of restlessness (Item 2), subjective
distress related to restlessness (Item 3), and global clinical assessment of
akathisia (Item 4). Results from the study reflect measurements with the BAS
performed on day 1, day 3, and day 5.
Trial Results
Overall, the results of the study showed that ACP-103 reduced akathisia
relative to placebo. There were no statistically significant differences
between ACP-103-treated and placebo-treated subjects for BAS Item 4 on day 5,
a priori defined as the primary outcome measure of the study, due to a large
placebo response. However, ACP-103 significantly reduced BAS Item 1 on day 5
(p = 0.04) and there were statistically significant improvements (p<0.05) or
statistical trends (p<0.1) on day 3 for Item 1 (p = 0.06), Item 2 (p = 0.02),
Item 3 (p = 0.09), and the BAS Total (all Items: p = 0.03).
The study was also used to explore the effects of ACP-103 on other
measures, which were not part of the inclusion criteria. No significant
effects were observed on extrapyramidal side effects, other than akathisia, or
on plasma prolactin levels. Also, as expected because of the short treatment
duration, there were no significant effects on positive or negative symptoms
of schizophrenia.
ACP-103 was safe and well tolerated and no serious adverse events were
reported in the study. Most of the adverse events were mild to moderate in
nature and there were no adverse events that led to discontinuation of the
study drug. Plasma levels of ACP-103 in patients in this study were
consistent with levels found in ACADIA's previous studies with ACP-103 both in
healthy volunteers and patients with Parkinson's disease. Furthermore, there
was no evidence of a pharmacokinetic interaction between haloperidol and
ACP-103.
Table Showing Results of ACP-103 on Haloperidol-Induced Akathisia Versus
Placebo as Measured by the Barnes Akathisia Scale (BAS)
Objective akathisia (Item 1), subjective awareness of restlessness
(Item 2), and subjective distress related to restlessness (Item 3) are rated
on a scale of 0 to 3. The global clinical assessment of akathisia (Item 4) is
rated on a scale of 0 to 5.
The table shows the mean change in the various measures of akathisia from
baseline across the study days for ACP-103-treated and the placebo-treated
groups. Negative figures indicate a reduction of that measure of akathisia.
For those items that showed a statistical trend or statistically significant
difference between ACP-103 and placebo, the p-values are shown (n.s. = not
significant).
Mean change from baseline
Barnes
Akathisia ACP-103 Placebo
Scale Day n = 14 n = 16 p-value
Item 1: 1 -0.1 -0.2 n.s.
Objective 3 -0.7 -0.3 0.06
Akathisia 5 -1.0 -0.5 0.04
Item 2: 1 -0.3 -0.1 n.s.
Subjective 3 -1.1 -0.3 0.02
Awareness of 5 -1.1 -0.6 n.s.
Restlessness
Item 3: 1 -0.6 -0.1 0.09
Subjective 3 -0.8 -0.3 0.09
Distress 5 -0.9 -0.9 n.s.
Related to
Restlessness
Item 4: 1 -0.4 -0.2 n.s.
Global 3 -1.1 -0.6 n.s.
Clinical 5 -1.4 -1.1 n.s.
Assessment of
Akathisia
Total 1 -1.4 -0.6 n.s.
Items 1-4 3 -3.6 -1.5 0.03
5 -4.4 -3.1 n.s.
About ACP-103
ACP-103 is a small molecule drug candidate that was discovered and is
being developed by ACADIA as an adjunctive therapy for schizophrenia. ACP-103
is a potent and selective serotonin 5-HT2A inverse agonist, a compound that
blocks the activity of this key target that plays an important role in the
treatment of neuropsychiatric disorders. By giving ACP-103 together with other
antipsychotic drugs, ACADIA believes that the drug candidate may improve the
clinical profile of existing antipsychotic drugs. ACADIA is currently
conducting a Phase II trial to explore the potential efficacy-enhancing and
dose-sparing effects of ACP-103 given adjunctively with risperidone, a
commonly prescribed atypical antipsychotic drug, and haloperidol. ACADIA is
also developing ACP-103 as a therapy for treatment-induced dysfunctions in
Parkinson's disease.
About Schizophrenia
Schizophrenia is a chronic disabling mental illness characterized by
disturbances such as hallucinations and delusions as well as a range of
negative symptoms. Despite the availability of a variety of current
antipsychotic drugs with worldwide sales exceeding $14 billion, many symptoms
associated with this disease are poorly addressed by existing therapies. In a
landmark government study released in September 2005, researchers found that
about three-quarters of the patients with schizophrenia who participated in
the study stopped taking the drugs they were on because of lack of efficacy or
intolerable side effects. Expanding the efficacy profile and reducing the
side effects of these drugs represent important medical advances in
schizophrenia therapy.
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical company utilizing innovative technology to
fuel drug discovery and clinical development of novel treatments for central
nervous system disorders. ACADIA currently has four drug programs in clinical
development as well as a portfolio of preclinical and discovery assets
directed at large unmet medical needs, including schizophrenia, Parkinson's
disease, neuropathic pain and glaucoma. All of the drug candidates in
ACADIA's product pipeline emanate from discoveries made using its proprietary
drug discovery platform. ACADIA's corporate headquarters is located in San
Diego, California and it maintains research and development operations in both
San Diego and Malmo, Sweden.
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 and related trials, the safety and efficacy
of ACADIA's drug candidates, and the benefits to be derived from ACADIA's
technology, approach and drug candidates, in each case, including ACP-103.
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 and commercialization, collaborations
with others and litigation. 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, 2004 filed with the United States Securities and Exchange
Commission as well as other 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.
Contacts:
ACADIA Pharmaceuticals Inc.
Lisa Barthelemy, Director, Investor Relations
Uli Hacksell, Ph.D., Chief Executive Officer
(858) 558-2871
