SAN DIEGO, Dec. 1 /PRNewswire-FirstCall/ —ACADIA Pharmaceuticals Inc.(Nasdaq: ACAD), a biopharmaceutical company utilizing innovative technology tofuel drug discovery and clinical development of novel treatments for centralnervous system disorders, today reported results from a Phase II study thatshowed that ACP-103 reduced haloperidol-induced akathisia, a debilitatingextrapyramidal side effect, in patients with schizophrenia.
This study is one of two Phase II clinical trials in ACADIA's programusing ACP-103 adjunctively with other antipsychotic drugs to provide animproved therapy for schizophrenia patients. The study involved 34 patientswith schizophrenia and was designed to evaluate the ability of ACP-103 totreat akathisia, a side effect often induced by antipsychotic drugs. Inaddition to this study, ACADIA is currently conducting a Phase II trial withup to 400 patients, which is designed to evaluate the ability of ACP-103 toimprove both the efficacy and safety profile of current antipsychotic drugs.
"We are encouraged by the ability of ACP-103 to treat haloperidol-inducedakathisia in patients with schizophrenia," said Uli Hacksell, Ph.D., ACADIA'sChief Executive Officer. "This study is an important demonstration of ourACP-103 adjunctive therapy approach to improve the quality of care forpatients suffering from schizophrenia."
Trial Design
The double-blind, randomized, placebo-controlled Phase II study enrolled34 patients with a clinical diagnosis of schizophrenia or schizoaffectivedisorder, who also experienced haloperidol-induced akathisia. Results fromthe study presented in the accompanying table are based on 30 patients whocompleted the study protocol and exclude 4 subjects who had major protocolviolations. Fourteen of these 30 patients received once-daily oraladministration of 60 mg of ACP-103 and 16 were administered placebo over afive-day period. Subjects were maintained on their pre-study dose ofhaloperidol during the course of the study.
Patients were evaluated using the Barnes Akathisia Scale (BAS), afour-item rating scale widely used to assess this particular side effect ofantipsychotic drugs. This scale consists of the following items: objectiveakathisia (Item 1), subjective awareness of restlessness (Item 2), subjectivedistress related to restlessness (Item 3), and global clinical assessment ofakathisia (Item 4). Results from the study reflect measurements with the BASperformed on day 1, day 3, and day 5.
Trial Results
Overall, the results of the study showed that ACP-103 reduced akathisiarelative to placebo. There were no statistically significant differencesbetween 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 largeplacebo response. However, ACP-103 significantly reduced BAS Item 1 on day 5(p = 0.04) and there were statistically significant improvements (p<0.05) orstatistical 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 othermeasures, which were not part of the inclusion criteria. No significanteffects were observed on extrapyramidal side effects, other than akathisia, oron plasma prolactin levels. Also, as expected because of the short treatmentduration, there were no significant effects on positive or negative symptomsof schizophrenia.
ACP-103 was safe and well tolerated and no serious adverse events werereported in the study. Most of the adverse events were mild to moderate innature and there were no adverse events that led to discontinuation of thestudy drug. Plasma levels of ACP-103 in patients in this study wereconsistent with levels found in ACADIA's previous studies with ACP-103 both inhealthy volunteers and patients with Parkinson's disease. Furthermore, therewas no evidence of a pharmacokinetic interaction between haloperidol andACP-103.
Table Showing Results of ACP-103 on Haloperidol-Induced Akathisia VersusPlacebo 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 ratedon a scale of 0 to 3. The global clinical assessment of akathisia (Item 4) israted on a scale of 0 to 5.
The table shows the mean change in the various measures of akathisia frombaseline across the study days for ACP-103-treated and the placebo-treatedgroups. Negative figures indicate a reduction of that measure of akathisia.For those items that showed a statistical trend or statistically significantdifference between ACP-103 and placebo, the p-values are shown (n.s. = notsignificant).
Mean change from baselineBarnesAkathisia ACP-103 PlaceboScale Day n = 14 n = 16 p-valueItem 1: 1 -0.1 -0.2 n.s.Objective 3 -0.7 -0.3 0.06Akathisia 5 -1.0 -0.5 0.04Item 2: 1 -0.3 -0.1 n.s.Subjective 3 -1.1 -0.3 0.02Awareness of 5 -1.1 -0.6 n.s.RestlessnessItem 3: 1 -0.6 -0.1 0.09Subjective 3 -0.8 -0.3 0.09Distress 5 -0.9 -0.9 n.s.Related toRestlessnessItem 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 ofAkathisiaTotal 1 -1.4 -0.6 n.s.Items 1-4 3 -3.6 -1.5 0.035 -4.4 -3.1 n.s.
About ACP-103
ACP-103 is a small molecule drug candidate that was discovered and isbeing developed by ACADIA as an adjunctive therapy for schizophrenia. ACP-103is a potent and selective serotonin 5-HT2A inverse agonist, a compound thatblocks the activity of this key target that plays an important role in thetreatment of neuropsychiatric disorders. By giving ACP-103 together with otherantipsychotic drugs, ACADIA believes that the drug candidate may improve theclinical profile of existing antipsychotic drugs. ACADIA is currentlyconducting a Phase II trial to explore the potential efficacy-enhancing anddose-sparing effects of ACP-103 given adjunctively with risperidone, acommonly prescribed atypical antipsychotic drug, and haloperidol. ACADIA isalso developing ACP-103 as a therapy for treatment-induced dysfunctions inParkinson's disease.
About Schizophrenia
Schizophrenia is a chronic disabling mental illness characterized bydisturbances such as hallucinations and delusions as well as a range ofnegative symptoms. Despite the availability of a variety of currentantipsychotic drugs with worldwide sales exceeding $14 billion, many symptomsassociated with this disease are poorly addressed by existing therapies. In alandmark government study released in September 2005, researchers found thatabout three-quarters of the patients with schizophrenia who participated inthe study stopped taking the drugs they were on because of lack of efficacy orintolerable side effects. Expanding the efficacy profile and reducing theside effects of these drugs represent important medical advances inschizophrenia therapy.
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical company utilizing innovative technology tofuel drug discovery and clinical development of novel treatments for centralnervous system disorders. ACADIA currently has four drug programs in clinicaldevelopment as well as a portfolio of preclinical and discovery assetsdirected at large unmet medical needs, including schizophrenia, Parkinson'sdisease, neuropathic pain and glaucoma. All of the drug candidates inACADIA's product pipeline emanate from discoveries made using its proprietarydrug discovery platform. ACADIA's corporate headquarters is located in SanDiego, California and it maintains research and development operations in bothSan Diego and Malmo, Sweden.
Forward-Looking Statements
Statements in this press release that are not strictly historical innature are forward-looking statements. These statements include but are notlimited to statements related to the progress and timing of ACADIA's drugdiscovery and development programs and related trials, the safety and efficacyof ACADIA's drug candidates, and the benefits to be derived from ACADIA'stechnology, approach and drug candidates, in each case, including ACP-103.These statements are only predictions based on current information andexpectations and involve a number of risks and uncertainties. Actual eventsor results may differ materially from those projected in any of suchstatements due to various factors, including the risks and uncertaintiesinherent in drug discovery, development and commercialization, collaborationswith 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 endedDecember 31, 2004 filed with the United States Securities and ExchangeCommission as well as other subsequent filings with the Securities andExchange Commission. You are cautioned not to place undue reliance on theseforward-looking statements, which speak only as of the date hereof. Thiscaution is made under the safe harbor provisions of the Private SecuritiesLitigation Reform Act of 1995. All forward-looking statements are qualifiedin their entirety by this cautionary statement and ACADIA undertakes noobligation to revise or update this press release to reflect events orcircumstances after the date hereof.
Contacts:
ACADIA Pharmaceuticals Inc.
Lisa Barthelemy, Director, Investor Relations
Uli Hacksell, Ph.D., Chief Executive Officer
(858) 558-2871