ACADIA Pharmaceuticals Initiates Phase III Trial of Pimavanserin for Adjunctive Treatment in Patients with Schizophrenia

SAN DIEGO—(BUSINESS WIRE)—Nov. 3, 2016—ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD), a biopharmaceutical companyfocused on innovative treatments that address unmet medical needs incentral nervous system disorders, today announced the initiation ofENHANCE-1, a Phase III study to evaluate pimavanserin for adjunctivetreatment of schizophrenia in patients with an inadequate response tocurrent antipsychotic therapy. Current antipsychotics approved forschizophrenia primarily target the dopaminergic pathway. As a selectiveserotonin inverse agonist (SSIA), pimavanserin is a new class ofantipsychotic medication with a distinct mechanism of action targetingserotonergic 5-HT_2A receptors while avoiding activity atdopamine and other receptors commonly targeted by other antipsychotics.

“About 30 percent of patients with schizophrenia do not achieve anadequate response to a single antipsychotic medication, and as a resultmore than one in four schizophrenia patients are treated with two ormore antipsychotics,” said Serge Stankovic, M.D., M.S.P.H., ACADIA’sExecutive Vice President, Head of Research and Development. “We believepimavanserin, through its highly selective mechanism of action, couldprovide an important new option for adjunctive treatment ofschizophrenia and improve clinical outcomes by both augmenting theefficacy of currently used antipsychotics and lessening the undesirableside effects associated with polypharmacy.”

About ENHANCE-1

ENHANCE-1 is a Phase III, six-week, randomized, double-blind,placebo-controlled, multi-center, outpatient study designed to examinethe efficacy and safety of adjunctive use of pimavanserin in patientswith schizophrenia who have not achieved an adequate response to theircurrent antipsychotic treatment. Approximately 380 patients will berandomized to receive pimavanserin, or placebo, orally, once daily, inaddition to their ongoing antipsychotic in a flexible dosing regimen.The starting daily dose of 20 mg of pimavanserin at baseline may beadjusted to 34 mg or 10 mg during the first three weeks of treatment.The primary endpoint of the study is the change from baseline to weeksix on the Positive and Negative Syndrome Scale (PANSS) total score.Following participation in ENHANCE-1, patients will be eligible toenroll in a 52-week open-label extension study.

About Schizophrenia

According to the National Mental Health Institute, approximately onepercent of the U.S. population develops schizophrenia during theirlifetime. Schizophrenia is a chronic, debilitating mental illnesscharacterized by disturbances in thinking, emotional reaction, andbehavior. These disturbances may include positive symptoms, such ashallucinations and delusions, and a range of negative symptoms,including loss of interest, emotional withdrawal and cognitivedisturbances. Current drugs used to treat schizophrenia have substantiallimitations, including severe side effects and a lack of efficacy on thefull range of symptoms of the disease.

According to the American Psychiatric Association, about 30 percent ofpatients with schizophrenia have inadequate response to antipsychoticmedications, meaning that they exhibit improvement, but continue to haveresidual hallucinations or delusions. As a result, about 25 to 50percent of schizophrenia patients are treated with two or moreantipsychotics. This polypharmacy has led to increased dose-related sideeffects and complicated dosing regimens that can further contribute topoor treatment compliance and subsequent relapse in these patients.

About Pimavanserin

Pimavanserin is a selective serotonin inverse agonist (SSIA)preferentially targeting 5-HT_2A receptors. These receptorsare thought to play an important role in schizophrenia. Pimavanserin isbeing evaluated in an extensive clinical development program by ACADIAacross multiple indications. Pimavanserin (34 mg) was approved for thetreatment of hallucinations and delusions associated with Parkinson’sdisease psychosis by the U.S. Food and Drug Administration in April 2016under the trade name NUPLAZID^®. NUPLAZID is not approved forthe adjunctive treatment of patients with schizophrenia.

About ACADIA Pharmaceuticals

ACADIA is a biopharmaceutical company focused on the development andcommercialization of innovative medicines to address unmet medical needsin central nervous system disorders. ACADIA maintains a website at www.acadia-pharm.comto which we regularly post copies of our press releases as well asadditional information and through which interested parties cansubscribe to receive e-mail alerts.

Forward-Looking Statements

Statements in this press release that are not strictly historical innature are forward-looking statements. These statements include but arenot limited to statements related to the progress and timing of ACADIA’sdrug discovery and development programs, the expected design and scopeof ACADIA’s clinical trials, and the benefits to be derived fromNUPLAZID (pimavanserin) and ACADIA’s product candidates, includingwhether pimavanserin could provide an important new option foradjunctive treatment of schizophrenia or improve clinical outcomes byaugmenting the efficacy of currently used antipsychotics and/orlessening the undesirable side effects associated with polypharmacy.These statements are only predictions based on current information andexpectations and involve a number of risks and uncertainties. Actualevents or results may differ materially from those projected in any ofsuch statements due to various factors, including the risks anduncertainties inherent in drug discovery, development, approval andcommercialization, and in collaborations with others, and the fact thatpast results of clinical trials may not be indicative of future trialresults. For a discussion of these and other factors, please refer toACADIA’s annual report on Form 10-K for the year ended December 31, 2015as well as ACADIA’s subsequent filings with the Securities and ExchangeCommission. 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 PrivateSecurities Litigation Reform Act of 1995. All forward-looking statementsare qualified in their entirety by this cautionary statement and ACADIAundertakes no obligation to revise or update this press release toreflect events or circumstances after the date hereof, except asrequired by law.

Important Safety Information and Indication forNUPLAZID (pimavanserin) tablets

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITHDEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated withantipsychotic drugs are at an increased risk of death. NUPLAZID is notapproved for the treatment of patients with dementia-related psychosisunrelated to the hallucinations and delusions associated withParkinson’s disease psychosis.

NUPLAZID is an atypical antipsychotic indicated for the treatment ofhallucinations and delusions associated with Parkinson’s diseasepsychosis.

QT Interval Prolongation: NUPLAZID prolongs the QT interval. The use ofNUPLAZID should be avoided in patients with known QT prolongation or incombination with other drugs known to prolong QT interval includingClass 1A antiarrhythmics or Class 3 antiarrhythmics, certainantipsychotic medications, and certain antibiotics. NUPLAZID should alsobe avoided in patients with a history of cardiac arrhythmias, as well asother circumstances that may increase the risk of the occurrence oftorsade de pointes and/or sudden death, including symptomaticbradycardia, hypokalemia or hypomagnesemia, and presence of congenitalprolongation of the QT interval.

Adverse Reactions: The most common adverse reactions (≥2%for NUPLAZID and greater than placebo) were peripheral edema (7%vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination(5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).

Drug Interactions: Strong CYP3A4 inhibitors (eg, ketoconazole)increase NUPLAZID concentrations. Reduce the NUPLAZID dose by one-half.Strong CYP3A4 inducers may reduce NUPLAZID exposure, monitor for reducedefficacy. Increase in NUPLAZID dosage may be needed.

Renal Impairment: No dosage adjustment for NUPLAZID is needed inpatients with mild to moderate renal impairment. Use of NUPLAZID is notrecommended in patients with severe renal impairment.

Hepatic Impairment: Use of NUPLAZID is not recommended in patients withhepatic impairment. NUPLAZID has not been evaluated in this patientpopulation.

Pregnancy: Use of NUPLAZID in pregnant women has not been evaluated andshould therefore be used in pregnancy only if the potential benefitjustifies the potential risk to the mother and fetus.

Pediatric Use: Safety and efficacy have not been established inpediatric patients.

Dosage and Administration: Recommended dose: 34 mg per day, taken orallyas two 17-mg tablets once daily, without titration.

For additional Important Safety Information, including boxed warning,please see the full Prescribing Information for NUPLAZID at https://www.nuplazid.com/pdf/NUPLAZID_Prescribing_Information.pdf.

Source: ACADIA Pharmaceuticals Inc.

Investor Contact:
ACADIA Pharmaceuticals Inc.
LisaBarthelemy
(858) 558-2871
ir@acadia-pharm.com
or
MediaContact:
Taft Communications
Ted Deutsch
(609)578-8765
ted@taftcommunications.com