ACADIA Pharmaceuticals Presents Data from the Phase II Study of Pimavanserin in Alzheimer’s Disease Psychosis at the Clinical Trials on Alzheimer’s Disease (CTAD) 2017 Meeting

Data Confirmed Significant Improvement in Psychosis in Patientswith Alzheimer’s Disease with Substantively Greater Benefit in Patientswith More Severe Psychotic Symptoms

SAN DIEGO—(BUSINESS WIRE)—Nov. 3, 2017—ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD), a biopharmaceutical companyfocused on the development and commercialization of innovative medicinesto address unmet medical needs in central nervous system (CNS)disorders, today announced the presentation of data from the Phase II-019 Study of pimavanserin in Alzheimer’s disease psychosis at the 10^thClinical Trials on Alzheimer’s Disease (CTAD) meeting in Boston. The-019 Study data are being presented at the symposium titled, “TheImportance of Serotonin in Alzheimer’s Disease Psychosis and the Role ofPimavanserin.”

Pimavanserin met the primary endpoint in the Phase II -019 Study,showing a statistically significant reduction in psychosis versusplacebo, as previously reported. Data presented at CTAD showed multiplesensitivity and responder analyses supportive of the primary result anddemonstrated substantively greater benefit in those patients with moresevere psychosis. Building on these data, ACADIA recently initiated thePhase III HARMONY study of pimavanserin in dementia-related psychosis.Dementia-related psychosis includes psychosis in Alzheimer’s disease,dementia with Lewy bodies, Parkinson’s disease dementia, vasculardementia, and frontotemporal dementia. There is no drug approved by theFDA for dementia-related psychosis. In October 2017, the FDA grantedBreakthrough Therapy Designation for pimavanserin for the treatment ofdementia-related psychosis.

“In the Phase II -019 Study, pimavanserin significantly reducedpsychosis in patients with Alzheimer’s disease without negativelyimpacting cognition,” said Clive Ballard, MBChB, MRCPsych,Pro-Vice-Chancellor and Executive Dean, University of Exeter MedicalSchool. “Pimavanserin also had a favorable tolerability profile comparedto known adverse effects of current antipsychotics. With no approvedtreatment for dementia-related psychosis, there is a significant unmetneed. The results of the study indicate that pimavanserin could be animportant new treatment option for this elderly and underserved patientpopulation.”

Key Findings from the Phase II -019 Study Presented at CTAD Symposium

The Phase II -019 Study data are being presented by Clive Ballard in thepresentation titled, “Clinical Trial of Pimavanserin in Alzheimer’sDisease Psychosis.” The Phase II -019 Study was a double-blind,placebo-controlled trial designed to evaluate the efficacy and safety ofpimavanserin in 181 patients with Alzheimer’s disease psychosis.Top-line results of the study were previously reported in December 2016.

Pimavanserin met the primary endpoint in the study, showing astatistically significant reduction in psychosis versus placebo asmeasured by the Neuropsychiatric Inventory-Nursing Home (NPI-NH)Psychosis score at week 6 of dosing (delta = 1.84, p=0.0451, effect size[Cohen’s d] = 0.32). The proportion of responders at week 6 that had anNPI-NH Psychosis score improvement of ≥ 30% was 55.2% forpimavanserin-treated patients versus 37.4% for placebo (p=0.0159).

Importantly, in the -019 Study, no detrimental effect was observed oncognition for pimavanserin-treated patients compared to placebo.Atypical antipsychotics have been associated with a statisticallysignificant acceleration of cognitive deterioration in patients withAlzheimer’s disease.

The pimavanserin and placebo groups did not separate statistically onthe secondary endpoints of the Alzheimer’s Disease Cooperative Study -Clinical Global Impression of Change (ADCS-CGIC) or the Cohen-MansfieldAgitation Inventory Short Form (CMAI-SF), nor on the exploratoryendpoints of the mean change in NPI-NH Psychosis score at week 12 or theAlzheimer’s Disease Cooperative Study - Activities of Daily Living(ADCS-ADL).

Data presented at CTAD from a pre-specified subgroup analysisdemonstrated a substantively larger and significant reduction inpsychosis in pimavanserin-treated patients with more severe psychosis,further underscoring the effect seen on the primary result.Approximately one-third of patients in the study had more severepsychotic symptoms (NPI-NH Psychosis score ≥12). In this subgroup,pimavanserin demonstrated a statistically significant reduction inpsychosis versus placebo on the NPI-NH Psychosis score at week 6 (delta= 4.43, p=0.0114, effect size [Cohen’s d] = 0.73). Additionally, theproportion of responders at week 6 that had an NPI-NH Psychosis scoreimprovement of ≥ 30% was 88.9% for pimavanserin-treated patients versus43.3% for placebo (p=0.0004).

Larger effects were also observed on the NPI-NH Psychosis score inpimavanserin-treated patients with prior antipsychotic use.

As previously reported, pimavanserin was well tolerated in this frailand elderly population and the safety profile was consistent with whathas been observed in previous studies.

Other Presentations at CTAD Symposium: “The Importance of Serotoninin Alzheimer’s Disease Psychosis and the Role of Pimavanserin”

The -019 Study data are being presented as part of a three-partsymposium. The symposium also includes a presentation by Stephen M.Stahl, MD, PhD, Adjunct Professor of Psychiatry, University ofCalifornia, San Diego, titled, “The Role of 5-HT_2A Receptorsin the Pharmacology of Alzheimer’s Disease Psychosis.” Serotonin 2Areceptors are highly expressed in brain regions critical for processingsensory information and performing executive functions. Circuitryperforming these functions may be deregulated when neurodegeneration hasoccurred. Selective 5-HT_2A inverse agonists/antagonists canbe used to restore balance to these deregulated circuits. Pimavanserinis a non-dopaminergic selective serotonin inverse agonist (SSIA)preferentially targeting 5-HT_2A receptors.

Furthermore, a presentation by Pierre N. Tariot, MD, Banner Alzheimer’sInstitute and University of Arizona College of Medicine, titled, “Reviewof Pimavanserin Clinical Results in the Context of HistoricalAlzheimer’s Disease Psychosis Trials,” reviews the results of thepimavanserin Phase II -019 Study compared to Alzheimer’s diseasepsychosis studies with other antipsychotics. Off-label use of atypicalantipsychotics is associated with modest and often equivocal efficacyand significant acceleration in cognitive decline in patients withdementia, as well as other adverse effects.

The symposium’s moderator is Jeffrey Cummings, MD, ScD, Director ofCleveland Clinic Lou Ruvo Center for Brain Health, who reviewsepidemiology, clinical phenomenology and psycho-social consequences ofdementia-related psychosis and the current treatment options andopportunities.

About Dementia-Related Psychosis

Around 8 million people in the United States are living with dementia,of which around 5.5 million people suffer from Alzheimer’s disease.Approximately half the people with dementia are diagnosed with thedisease. Studies suggest that approximately 30% of patients withdementia have psychosis, commonly consisting of hallucinations anddelusions. Dementia-related psychosis includes psychosis in Alzheimer’sdisease, dementia with Lewy bodies, Parkinson’s disease dementia,vascular dementia, and frontotemporal dementia. Serious consequenceshave been associated with severe or persistent psychosis in patientswith dementia such as repeated hospital admissions, earlier progressionto nursing home care, more rapid progression of dementia, and increasedrisk of morbidity and mortality.

Phase III HARMONY Study

Pimavanserin is currently being evaluated in a Phase III study, HARMONY,which is designed to evaluate its efficacy and safety for the treatmentof hallucinations and delusions associated with dementia-relatedpsychosis. The objective of the study is to evaluate the ability ofpimavanserin to prevent relapse of psychotic symptoms in a broadpopulation of patients with the most common subtypes of dementia:Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s diseasedementia, vascular dementia and frontotemporal dementia.

The FDA has granted Breakthrough Therapy Designation for pimavanserinfor the treatment of dementia-related psychosis. No drug is approved bythe FDA for dementia-related psychosis.

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^®, and is the first and only medicine approvedfor this indication. NUPLAZID is not approved for the treatment ofpatients with dementia-related psychosis.

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 pimavanserin could be an important new treatment forelderly and underserved patients with dementia-related psychosis;whether selective 5-HT2A inverse agonists/antagonists, such aspimavanserin, can be used to restore balance to brain regions criticalfor processing sensory information and performing executive functions;and the timing or results of future studies involving pimavanserin.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 the fact that past results of clinical trials maynot be indicative of future trial results. For a discussion of these andother factors, please refer to ACADIA’s annual report on Form 10-K forthe year ended December 31, 2016 as well as ACADIA’s subsequent filingswith the Securities and Exchange Commission. You are cautioned not toplace undue reliance on these forward-looking statements, which speakonly as of the date hereof. This caution is made under the safe harborprovisions of the Private Securities Litigation Reform Act of 1995. Allforward-looking statements are qualified in their entirety by thiscautionary statement and ACADIA undertakes no obligation to revise orupdate this press release to reflect events or circumstances after thedate hereof, except as required 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.

Contraindication: NUPLAZID is contraindicated in patients with a historyof a hypersensitivity reaction to pimavanserin or any of its components.Rash, urticaria, and reactions consistent with angioedema (e.g., tongueswelling, circumoral edema, throat tightness, and dyspnea) have beenreported.

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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