ACADIA Pharmaceuticals Initiates Phase 3 CLARITY Program with Pimavanserin as Adjunctive Treatment for Major Depressive Disorder

SAN DIEGO—(BUSINESS WIRE)—Apr. 25, 2019—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 initiation of the Phase 3 CLARITY-2 studyand plans to initiate the Phase 3 CLARITY-3 study in the upcomingmonths. These studies will evaluate the efficacy and safety ofpimavanserin as adjunctive treatment in patients with major depressivedisorder (MDD) who have an inadequate response to standardantidepressant therapy with either a selective serotonin reuptakeinhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor(SNRI). Pimavanserin is a selective serotonin inverse agonistpreferentially targeting 5-HT_2A receptors, which may play arole in depression.

“We are pleased to announce the initiation of the Phase 3 CLARITYprogram. The results observed in the original Phase 2 CLARITY studyshowed significant promise for patients with MDD, including asignificant antidepressant response, improvement in disability,decreased daytime sleepiness, no meaningful weight gain, and improvedsexual function,” said Serge Stankovic, M.D., M.S.P.H., ACADIA’sPresident. “We believe pimavanserin has the potential to be a veryimportant treatment option for the millions of MDD patients where thereremains unmet medical need. Based on feedback we received from the U.S.FDA, if we’re successful in the Phase 3 program, we plan to use thePhase 2 CLARITY study and positive study results from at least one ofthese two Phase 3 studies to support a supplemental NDA submission.”

About CLARITY-2 and CLARITY-3
CLARITY-2 and CLARITY-3 areboth 6-week, parallel-designed, randomized, double-blind,placebo-controlled, multi-center studies designed to evaluate theefficacy and safety of pimavanserin as adjunctive treatment in patientswith MDD who have an inadequate response to standard antidepressanttherapy with either a SSRI or a SNRI. CLARITY-2 will enrollapproximately 280 patients in the U.S. and CLARITY-3 will enrollapproximately 280 patients internationally. Patients in both studieswill be randomized to receive six weeks of oral treatment with either 34mg of pimavanserin or placebo, once daily, in addition to their ongoingantidepressant. The primary endpoint in both studies is the change frombaseline on the 17-item Hamilton Depression Rating Scale (HAMD-17) totalscore.

Patients who complete the CLARITY-2 or CLARITY-3 studies will beeligible to participate in a 52-week open-label extension study toevaluate the long-term safety and tolerability of pimavanserin.

About CLARITY
CLARITY was a Phase 2, 10-week, randomized,double-blind, placebo-controlled, multi-center, 2-stage sequentialparallel comparison design study that evaluated the safety,tolerability, and efficacy of pimavanserin (34 mg once daily) as anadjunctive treatment in patients with MDD who had an inadequate responseto a stable dose of standard antidepressant therapy with either a SSRIor a SNRI. The study was conducted in collaboration with the MGHClinical Trials Network & Institute and randomized 207 patients across28 clinical research centers in the U.S.

In the trial, pimavanserin met the overall primary endpoint of theweighted average results of Stage 1 and Stage 2 by significantlyreducing the HAMD-17 total score compared to placebo (p=0.039). On thekey secondary endpoint, pimavanserin demonstrated statisticallysignificant reductions compared to placebo in the Sheehan DisabilityScale score (p=0.004). Positive results were also observed for sevenother secondary endpoints including the Karolinska Sleepiness Scale(p=0.0205) and the Massachusetts General Hospital Sexual FunctioningIndex (p=0.0003).

About Major Depressive Disorder (MDD)
According to theNational Institute of Mental Health, MDD affects approximately 16million adults in the U.S.¹, with approximately 2.5 millionadults treated with adjunctive therapy^2,3. MDD is a conditioncharacterized by depressive symptoms such as a depressed mood or a lossof interest or pleasure in daily activities for more than two weeks, aswell as impaired social, occupational or other important functioning.The majority of people who suffer from MDD do not respond adequately toinitial antidepressant therapy⁴.

About Pimavanserin
Pimavanserin is a selective serotonininverse agonist preferentially targeting 5-HT_2A receptors.These receptors are thought to play an important role in depression,psychosis, and other neuropsychiatric disorders. ACADIA is evaluatingpimavanserin in an extensive clinical development program acrossmultiple indications with significant unmet need includingdementia-related psychosis, schizophrenia inadequate response,schizophrenia-negative symptoms, and major depressive disorder.Pimavanserin was approved for the treatment of hallucinations anddelusions associated with Parkinson’s disease psychosis by the U.S. Foodand Drug Administration in April 2016 under the trade name NUPLAZID^®.NUPLAZID is not approved for the adjunctive treatment of patients withmajor depressive disorder.

About ACADIA Pharmaceuticals
ACADIA is a biopharmaceuticalcompany focused on the development and commercialization of innovativemedicines to address unmet medical needs in central nervous systemdisorders. ACADIA has developed and commercialized the first and onlymedicine approved for the treatment of hallucinations and delusionsassociated with Parkinson’s disease psychosis. ACADIA also has ongoingclinical development efforts in additional areas with significant unmetneed, including dementia-related psychosis, schizophrenia inadequateresponse, schizophrenia-negative symptoms, major depressive disorder,and Rett syndrome. This press release and further information aboutACADIA can be found at: www.acadia-pharm.com.

Forward-Looking Statements
Statements in this press releasethat are not strictly historical in nature are forward-lookingstatements. These statements include, but are not limited to, statementsrelated to: the potential benefits of pimavanserin as adjunctivetreatment for MDD or other central nervous system disorders as well asthe potential results of clinical trials of pimavanserin in otherindications. These statements are only predictions based on currentinformation 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, 2018 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.

References

¹National Institute of Mental Health. (2017). MajorDepression. Retrieved from http://www.nimh.nih.gov/health/statistics/major-depression.shtml

²IMS NSP, NPA, NDTI MAT-24 month data through Aug-2017.

³PLOS One, Characterization of Treatment Resistant DepressionEpisodes in a Cohort of Patients from a US Commercial Claims Database,Oct 2013, Vol 8, Issue 10.

⁴Rush AJ, et al. (2007) Am J. Psychiatry 163:11, pp.1905-1917 (STAR*D Study).

Important Safety Information and Indication forNUPLAZID (pimavanserin)

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 not approved for the treatment of patients withdementia-related psychosis unrelated to the hallucinations anddelusions associated with Parkinson’s disease psychosis.

Contraindication: NUPLAZID is contraindicated in patients with ahistory of a hypersensitivity reaction to pimavanserin or any of itscomponents. Rash, urticaria, and reactions consistent with angioedema(e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea)have been reported.

QT Interval Prolongation: NUPLAZID prolongs the QT interval. Theuse of NUPLAZID should be avoided in patients with known QT prolongationor in combination with other drugs known to prolong QT intervalincluding Class 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% forNUPLAZID and greater than placebo) were peripheral edema (7% vs 2%),nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).

Drug Interactions: Coadministration with strong CYP3A4 inhibitors(e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID doseto 10 mg taken orally as one tablet once daily. Coadministration withstrong CYP3A4 inducers may reduce NUPLAZID exposure. Monitor patientsfor reduced efficacy and an increase in NUPLAZID dosage may be needed.

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

Dosage and Administration: Recommended dose: 34 mg taken orallyonce daily, without titration.

Indication: NUPLAZID is an atypical antipsychotic indicated forthe treatment of hallucinations and delusions associated withParkinson’s disease psychosis.

You are encouraged to report negative side effects of prescription drugsto the FDA. Visit www.fda.gov/medwatch,or call 1-800-FDA-1088. You can also call ACADIA Pharmaceuticals Inc. at1-844-4ACADIA (1-844-422-2342).

NUPLAZID is available as 34 mg capsules and 10 mg tablets.

Please see the full Prescribing Information including Boxed WARNING forNUPLAZID at https://www.nuplazid.com/pdf/NUPLAZID_Prescribing_Information.pdf.

Source: ACADIA Pharmaceuticals Inc.

Investor Contact:

ACADIA Pharmaceuticals Inc.
MarkJohnson, CFA
(858) 261-2771
ir@acadia-pharm.com

Media Contact:

ACADIA Pharmaceuticals Inc.
MaurissaMessier
(858) 768-6068
media@acadia-pharm.com