Conference Call Scheduled for Today, March 23, 2006 at 5:00 p.m. Eastern Time
SAN DIEGO, March 23 /PRNewswire-FirstCall/ —ACADIA Pharmaceuticals Inc.(Nasdaq: ACAD) today reported results from its Phase II clinical trial ofACP-103 in patients with Parkinson's disease suffering from treatment-inducedpsychosis. ACP-103 met the primary endpoint of the clinical trial, which wasmotoric tolerability as measured by the Unified Parkinson's Disease RatingScale (UPDRS), by demonstrating that it did not worsen motor function inpatients with Parkinson's disease. The trial also evaluated secondaryendpoints of antipsychotic efficacy using three different rating scales, andACP-103 demonstrated antipsychotic effects on two of these rating scales.ACP-103 was safe and well tolerated in patients with Parkinson's disease.ACADIA also provided an update on its ongoing open-label extension study forACP-103 in patients with Parkinson's disease and reported that some patientshave been treated with ACP-103 for over one year.
"The trial results are encouraging and suggest that ACP-103 may provide animportant advance in the therapy for patients with Parkinson's disease. Thedrug treatment of Parkinson's disease produces a high incidence ofhallucinations and paranoid delusions, which in turn are the most commoncauses for nursing home placement. Treatment for this is inadequate. ACP-103appears to combine efficacy, tolerability and safety in a way that currenttreatment paradigms do not," said Joseph H. Friedman, M.D., PrincipalInvestigator and Clinical Professor at Brown University. "Currently, thetreatment options for these patients are limited. Whereas antipsychotics areused off-label, it is a challenge for physicians to find the balance betweenantipsychotic activity and tolerability. There is a large unmet medical needfor new therapies that will effectively treat the psychosis and otherdysfunctions that result from the use of dopamine replacement drugs withoutcausing excess sedation, orthostatic hypotension or impairing motor function."
The Phase II clinical trial was a multi-center, double-blind,placebo-controlled study designed to evaluate the motoric tolerability,antipsychotic efficacy, and safety of ACP-103 in patients with Parkinson'sdisease suffering from treatment-induced psychosis. The trial enrolled 60patients at multiple clinical sites in the United States. The study involvedonce-daily oral administration of either ACP-103 or placebo for a 28-dayperiod to patients who also received their stable dopamine replacementtherapy. The design of the study permitted escalation of the initial 20 mgdose of ACP-103 to 40 mg and then to 60 mg at two scheduled intervals duringthe study. Fewer patients on ACP-103 were escalated to higher doses ascompared to placebo-treated patients, and the mean total dose of ACP-103 wassignificantly less than the mean total dose of placebo (p=0.05). Thisdifference in dose escalation between the two groups as indicated byphysicians' answers to a trial questionnaire was mainly due to positiveclinical responses in those patients who were not escalated rather than anydose limitation due to tolerability.
The primary endpoint of the clinical trial was met by the demonstrationthat there was no statistical difference between the ACP-103-treated group andthe placebo-treated group in motoric function as measured by subsections PartsII and III of the UPDRS (p=0.22). The primary endpoint evaluated absolutechange from baseline to study day 28 between the ACP-103 and placebo groups onthe UPDRS for the intent-to-treat population. The study was designed with 95%statistical power to detect a clinically meaningful 5 point difference betweenACP-103 and placebo as measured by subsections Parts II and III of the UPDRS.This lack of statistical significance between ACP-103 and placebo-treatedgroups showed that ACP-103 did not worsen motor functions in patients withParkinson's disease suffering from treatment-induced psychosis.
The study also included secondary endpoints of antipsychotic efficacyusing three different rating scales: Part I of the UPDRS, which measuresmental impairments, including an item rating severity of psychosis; the Scalefor the Assessment of Positive Symptoms (SAPS), which measures hallucinationsand delusions; and the Clinical Global Impression - Severity of Illness scale(CGI-S), which reflects a general assessment of a patient's overall severityof mental illness.
ACP-103 demonstrated statistically significant improvement compared toplacebo on the UPDRS Part I (p<0.05) and this result was attributable toeffects on hallucinations and delusions. ACP-103 also showed a statisticaltrend compared to placebo on total SAPS score (p<0.09) as measured by theabsolute change from baseline. Post-hoc analyses showed a significantdifference from placebo for ACP-103 using a relative percent change frombaseline analysis for the SAPS (p=0.05). ACP-103 did not show a significanteffect as compared to placebo on the CGI-S. However, more patients in theACP-103-treated group (42%) showed a reduction in CGI-S score as compared topatients in the placebo-treated group (18%).
Secondary Endpoint Measures of Antipsychotic Efficacy
The following table shows the mean baseline scores and mean change scoresfrom baseline to study day 28 for the ACP-103 and placebo-treated groups. Thedata are based on the per protocol population using the observed cases andexclude patients with major protocol deviations. Negative figures under meanchange indicate improvements. The p-values reflect the difference betweenACP-103 and placebo (n.s.=not significant).
ACP-103 Placebo(n=24) (n=28)Mean Mean Mean MeanBaseline Change Baseline Change p-valueUPDRS Part I 6.6 -1.5 6.3 -0.5 p<0.05SAPS Total 16.7 -5.6 17.9 -1.2 p<0.09CGI-S 4.3 -0.6 3.8 0 n.s.
The study also assessed other complications of Parkinson's disease therapyusing the UPDRS Part IV, which measures clinical fluctuations (i.e., on/offperiods), dyskinesias, and other complications common to the dopaminergictreatments used in Parkinson's therapy. ACP-103 showed a statistical trendfor improvement versus placebo on the UPDRS Part IV (p<0.06), suggesting thatit may be useful in treating a variety of dysfunctions in Parkinson's disease.
ACP-103 was safe and well tolerated in patients with Parkinson's diseasesuffering from treatment-induced psychosis. There were no treatment-relatedserious adverse events in the study as designated by the investigators. Mostof the adverse events were mild to moderate in nature and the frequency ofadverse events were generally similar across the ACP-103 and placebo-treatedgroups. The most common adverse events that were experienced by theACP-103-treated group (24%) and the placebo-treated group (32%) were nervoussystem disorders such as somnolence, headache and dizziness. ACP-103 was safeacross a wide variety of clinical measures assessed throughout the study,including ECG, vital signs, hematology, urinalysis and clinical chemistry.
Open-Label Extension Study of ACP-103
ACADIA is also conducting an ongoing open-label extension study involvingthe extended use of ACP-103 in patients with Parkinson's disease who havecompleted the aforementioned Phase II trial and may, in the opinion of thetreating physician, benefit from continued treatment with ACP-103. Theextension study is designed to determine the safety of ACP-103 duringlong-term administration. A total of 39 patients enrolled in the open-labelstudy, out of a total of approximately 45 patients who were eligible followingthe initiation of this study. Currently, 26 patients are participating in theextension study. Ten of these patients have been on ACP-103 for at least sixmonths and three of these patients have continued treatment with ACP-103 forover one year. ACP-103 has been safe and well tolerated in these patients andthere have been no treatment-related serious adverse events reported.
Conference Call and Webcast Information
ACADIA will host a conference call and webcast today, March 23, 2006, at5:00 p.m. Eastern Time to discuss the results from the ACP-103 Phase IIclinical trial. The conference call can be accessed by dialing 800-299-9630for participants in the U.S. or Canada and 617-786-2904 for internationalcallers (reference passcode 20101257). A telephone replay of the conferencecall may be accessed through April 6, 2006 by dialing 888-286-8010 for callersin the U.S. or Canada and 617-801-6888 for international callers (referencepasscode 34870055). The conference call also will be webcast live on ACADIA'swebsite, www.acadia-pharm.com, under the investors section and will bearchived there until April 6, 2006.
About ACP-103
ACP-103 is a proprietary, potent and selective 5-HT2A receptor inverseagonist, which acts to block the activity of this key serotonin receptor.ACADIA has demonstrated that ACP-103 is safe and well tolerated in preclinicalstudies and in Phase I and initial Phase II clinical trials. ACADIA is alsodeveloping ACP-103 as an adjunctive therapy for schizophrenia.
About Parkinson's Disease
Parkinson's disease is a chronic, progressive neurological disorder thatresults from the degeneration of neurons in a region of the brain thatcontrols movement. It is marked by a number of debilitating symptoms,including tremors, limb stiffness, slowness of movements, and difficultieswith posture and balance. According to the American Parkinson's DiseaseAssociation, over 1.5 million people in the United States suffer fromParkinson's disease. Patients with Parkinson's disease are currently treatedwith dopamine replacement therapies and the use of these agents frequentlyresults in a range of drug-induced side effects, including neuropsychiatricabnormalities such as psychotic symptoms as well as uncontrollable andexcessive movements of the limbs referred to as dyskinesias.
There have been numerous attempts to use existing antipsychotic drugs totreat the neuropsychiatric abnormalities caused by the treatment ofParkinson's disease. Because antipsychotic agents worsen the pre-existingbrain dopamine deficit and often produce disabling side effects, these drugsare generally not well tolerated by patients with Parkinson's disease.Currently, there is a large unmet medical need for therapies that willeffectively control or eliminate the side effects that result from the use ofdopamine replacement therapies, without impairing motor function in thesepatients.
About ACADIA Pharmaceuticals
ACADIA Pharmaceuticals is a biopharmaceutical company utilizing innovativetechnology to fuel drug discovery and clinical development of novel treatmentsfor central nervous system disorders. ACADIA currently has four drug programsin clinical development as well as a portfolio of preclinical and discoveryassets directed at large unmet medical needs, including schizophrenia,Parkinson's disease, neuropathic pain, and glaucoma. All of the drugcandidates in ACADIA's product pipeline emanate from discoveries made usingits proprietary drug discovery platform. ACADIA's corporate headquarters islocated in San Diego, California and it maintains research and developmentoperations in both San 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 potential for ACP-103 as a therapy forcertain patients with Parkinson's disease or its utility in treating certaindysfunctions. These statements are only predictions based on currentinformation and expectations and involve a number of risks and uncertainties.Actual events or results may differ materially from those projected in any ofsuch statements due to various factors, including the risks and uncertaintiesinherent in drug discovery, development and commercialization. In particular,results from Phase II clinical trials are not guarantees of results in anyfuture trials or of ACADIA's ability to obtain regulatory approval forACP-103. For a discussion of these and other factors, please refer to ACADIA'sannual report on Form 10-K for the year ended December 31, 2005 filed with theUnited States Securities and Exchange Commission as well as other subsequentfilings with the Securities and Exchange Commission. You are cautioned not toplace undue reliance on these forward-looking statements, which speak only asof the date hereof. This caution is made under the safe harbor provisions ofthe Private Securities Litigation Reform Act of 1995. All forward-lookingstatements are qualified in their entirety by this cautionary statement andACADIA undertakes no obligation to revise or update this press release toreflect 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