ACADIA Pharmaceuticals Initiates Phase III Study of Pimavanserin in Dementia-Related Psychosis

• Dementia-Related Psychosis Includes Psychosis in Patients withAlzheimer’s Disease, Dementia with Lewy Bodies, Parkinson’s DiseaseDementia, Vascular Dementia, and Frontotemporal Dementia

• FDA Grants Breakthrough Therapy Designation to Pimavanserin forDementia-Related Psychosis
• Conference Call to Be Held Today at 5:00 pm ET to Discuss Phase IIIDevelopment Program

SAN DIEGO—(BUSINESS WIRE)—Oct. 4, 2017—ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD) today announced theinitiation of HARMONY, a Phase III study to evaluate pimavanserin forthe treatment of hallucinations and delusions associated withdementia-related psychosis, a serious medical condition for which thereis no therapy approved by the U.S. Food and Drug Administration (FDA).The company also announced that the FDA has granted Breakthrough TherapyDesignation to pimavanserin for dementia-related psychosis.Dementia-related psychosis includes psychosis in patients withAlzheimer’s disease, dementia with Lewy bodies, Parkinson’s diseasedementia, vascular dementia, and frontotemporal dementia.

If the clinical development program is successful, and pimavanserin isultimately approved by the FDA for the treatment of dementia-relatedpsychosis, it would represent a significant expansion of the approveduse of pimavanserin. Currently, pimavanserin is the only drug approvedby the FDA for the treatment of hallucinations and delusions associatedwith Parkinson’s disease psychosis. It is marketed under the trade nameNUPLAZID^®.

“We are pleased the FDA has agreed to an efficient development path forpimavanserin in this broad indication and granted Breakthrough TherapyDesignation in recognition of this serious unmet need,” said SergeStankovic, M.D., M.S.P.H., ACADIA’s Executive Vice President, Head ofResearch and Development. “Initiation of our Phase III study issupported by clinical and preclinical evidence of pimavanserin’santipsychotic activity without detrimental effects on cognitive functionor other side effects associated with antipsychotics currently usedoff-label for this indication.”

Around 8 million people in the United States are living with dementiaand approximately half are diagnosed with the disease. Studies suggestthat approximately 30% of patients with dementia have psychosis,commonly consisting of hallucinations and delusions. Seriousconsequences have been associated with severe or persistent psychosis inpatients with dementia such as repeated hospital admissions, earlierprogression to nursing home care, more rapid progression of dementia,and increased risk of morbidity and mortality.

“With receipt of FDA’s Breakthrough Therapy Designation forpimavanserin, we are able to accelerate this important program,” saidSteve Davis, President and Chief Executive Officer of ACADIA.“Pimavanserin has a unique biological mechanism that distinguishes itfrom any other antipsychotic. We believe the profile we observed in ourPhase II -019 Study in Alzheimer’s disease psychosis could beparticularly beneficial in this elderly underserved population. In thatstudy, pimavanserin demonstrated antipsychotic effect without impairingcognition and we also observed a very favorable tolerability profile. Wewere very excited to be the first and only FDA approved drug for thetreatment of Parkinson’s disease psychosis and are equally excited aboutthe potential to help many more patients suffering from dementia-relatedpsychosis.”

The initiation of the pivotal study in dementia-related psychosis,referred to as HARMONY, follows an End-of-Phase II Meeting and agreementwith the FDA on the clinical development plan and the design of thePhase III study. ACADIA believes that robust positive results from onePhase III study together with supportive data from prior studies withpimavanserin could serve as the basis of a supplementary New DrugApplication (sNDA) for the treatment of hallucinations and delusionsassociated with dementia-related psychosis.

Breakthrough Therapy Designation serves to expedite the development andreview by the FDA of drugs that are intended to treat a serious orlife-threatening disease or condition. The Breakthrough TherapyDesignation for dementia-related psychosis was granted, in part, basedon results of ACADIA’s Phase II -019 Study with pimavanserin inAlzheimer’s disease psychosis and results of the company’s Phase III-020 Study with pimavanserin in Parkinson’s disease psychosis. This isthe second Breakthrough Therapy Designation for pimavanserin.

About the Phase III HARMONY Study

HARMONY is a Phase III, randomized, double-blind, placebo-controlledstudy, evaluating the efficacy and safety of pimavanserin for thetreatment of hallucinations and delusions associated withdementia-related psychosis. The objective of the study is to evaluatethe ability of pimavanserin to prevent relapse of psychotic symptoms ina broad population of patients with the most common subtypes ofdementia: Alzheimer’s disease, dementia with Lewy bodies, Parkinson’sdisease dementia, vascular dementia and frontotemporal dementia. Thestudy will be conducted globally and is expected to enroll approximately360 patients.

The study includes a 12-week open-label stabilization period duringwhich patients with dementia-related psychosis will be treated withpimavanserin 34 mg once daily. Dose reduction to 20 mg once daily willbe allowed if clinically justified. Following the 12-week stabilizationperiod, patients who meet pre-specified criteria for treatment responsewill then be randomized into the double-blind period of the study tocontinue their pimavanserin dose (34 mg or 20 mg per day) or be switchedto placebo and followed for up to 26 weeks or until a relapse ofpsychosis occurs. The primary endpoint in the study is time to relapsein the double-blind period.

Clinical Data Supporting Phase III Trial Design

The Phase III development plan is supported by data from two completedclinical studies. As previously announced, in the completed Phase II-019 Study of pimavanserin in Alzheimer’s disease psychosis,pimavanserin demonstrated clinically meaningful and statisticallysignificant efficacy of pimavanserin 34 mg over placebo on the primaryendpoint as measured by the Neuropsychiatric Inventory-Nursing Home(NPI-NH) psychosis score at week 6 of dosing (p=0.0451). Results fromthis Phase II study in Alzheimer’s disease psychosis will be presentedat the 10^th Clinical Trials on Alzheimer’s Disease (CTAD)Meeting on November 3, 2017 in Boston.

Additional clinical evidence for efficacy of pimavanserin indementia-related psychosis was observed in the Phase III -020 Study inpatients with Parkinson’s disease psychosis. Approximately a quarter ofthe patients enrolled in the -020 Study also suffered from milddementia. In a pre-specified subgroup analysis of these patients, thosetreated with pimavanserin observed a significant improvement inpsychosis compared to placebo. This effect was larger than the overallaverage effect observed in the study.

Other

ACADIA also announced that due to the potential overlap of clinicalsites and study participants between its Phase III HARMONYdementia-related psychosis study and the Company’s ongoing Phase IISERENE study of pimavanserin in Alzheimer’s disease agitation, it hasdecided to discontinue enrollment of new patients in the SERENE study.Patients already enrolled will complete the study as planned.Discontinuation of enrollment in the SERENE study will avoid potentialinterference between the two studies and enable ACADIA to focus externaland internal resources on the Phase III dementia-related psychosisprogram.

Conference Call and Webcast Information

ACADIA management will hold a conference call and webcast today at 5:00p.m. Eastern Time. The conference call may be accessed by dialing844-821-1109 for participants in the U.S. or Canada and 830-865-2550 forinternational callers (reference passcode 94813084). A telephone replayof the conference call may be accessed through October 18, 2017 bydialing 855-859-2056 for callers in the U.S. or Canada and 404-537-3406for international callers (reference passcode 94813084). The conferencecall also will be webcast live on ACADIA’s website, www.acadia-pharm.com,under the investors section and will be archived there through October18, 2017.

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 dementia-related psychosis.Pimavanserin is being evaluated in an extensive clinical developmentprogram by ACADIA across multiple indications. Pimavanserin (34 mg) wasapproved for the treatment of hallucinations and delusions associatedwith Parkinson’s disease psychosis by the FDA in 2016 under the tradename NUPLAZID^®. NUPLAZID is not approved for the treatment ofpatients with dementia-related psychosis.

About Dementia-Related Psychosis

Around 8 million people in the United States are living with dementiaand approximately half are diagnosed with the disease. Studies suggestthat approximately 30% of patients with dementia have psychosis,commonly consisting of hallucinations and delusions. Dementia-relatedpsychosis is a serious medical condition for which there is currently noFDA-approved therapy. Dementia-related psychosis includes psychosis inAlzheimer’s disease, dementia with Lewy bodies, Parkinson’s diseasedementia, vascular dementia, and frontotemporal dementia. Seriousconsequences have been associated with severe or persistent psychosis inpatients with dementia such as repeated hospital admissions, earlierprogression to nursing home care, more rapid progression of dementia,and increased risk of morbidity and mortality.

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 benefits to be derived fromNUPLAZID (pimavanserin); the utility of pimavanserin in indicationsother than hallucinations and delusions associated with Parkinson’sdisease psychosis, including indications falling within dementia-relatedpsychosis; whether the profile observed in the Phase II -019 Study inAlzheimer’s disease psychosis will be beneficial to elderly patientswith dementia-related psychosis; whether the development path fordementia-related psychosis will be efficient; whether NUPLAZID willreceive a broad indication for dementia-related psychosis; whether theapproved use of NUPLAZID will be significantly expanded; whetherpositive results from one Phase III study of pimavanserin indementia-related psychosis will be sufficient basis for the filing orapproval of an sNDA for that indication; the timing of presentation ofclinical data and results; and the timing or results of future studiesinvolving pimavanserin. These statements are only predictions based oncurrent information and expectations and involve a number of risks anduncertainties. Actual events or results may differ materially from thoseprojected in any of such statements due to various factors, includingthe risks and uncertainties inherent in drug discovery, development,approval and commercialization, and the fact that past results ofclinical trials may not be indicative of future trial results. For adiscussion of these and other factors, please refer to ACADIA’s annualreport on Form 10-K for the year ended December 31, 2016 as well asACADIA’s subsequent filings with the Securities and Exchange Commission.You are cautioned not to place undue reliance on these forward-lookingstatements, which speak only as of the date hereof. This caution is madeunder the safe harbor provisions of the Private Securities LitigationReform Act of 1995. All forward-looking statements are qualified intheir entirety by this cautionary statement and ACADIA undertakes noobligation to revise or update this press release to reflect events orcircumstances after the date hereof, except as required by law.

Important Safety Information and Indication forNUPLAZID (pimavanserin) tablets
WARNING: INCREASEDMORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Elderlypatients with dementia-related psychosis treated with antipsychoticdrugs are at an increased risk of death. NUPLAZID is not approved forthe treatment of patients with dementia-related psychosis unrelated tothe hallucinations and delusions associated with Parkinson’s diseasepsychosis.

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

Contraindication: NUPLAZID is contraindicated in patients with a historyof hypersensitivity reaction to pimavanserin or any of its components.Reactions have included rash, urticaria, tongue swelling, circumoraledema, and throat tightness.

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.

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