ACADIA Pharmaceuticals Announces Positive Top-line Results from Phase 2 CLARITY Trial of Pimavanserin for Adjunctive Treatment in Patients with Major Depressive Disorder (MDD)

- Pimavanserin met primary endpoint with statistically significantoverall improvement in HAMD-17 total score compared to placebo (p=0.039)

- Pimavanserin met key secondary endpoint with statisticallysignificant overall improvement in Sheehan Disability Scale compared toplacebo (p=0.004)

- Positive results also observed on seven additional secondaryendpoints including responder rate, improvement in sexual function, andreduction in daytime sleepiness

- ACADIA to initiate Phase 3 program in adjunctive MDD in 1H 2019

- Conference call and webcast to be held today at 8:30 a.m. EasternTime

SAN DIEGO—(BUSINESS WIRE)—Oct. 31, 2018—ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD) today announced positivetop-line results from CLARITY, a randomized, double-blind,placebo-controlled, multi-center, sequential parallel comparison design(SPCD) study in major depressive disorder (MDD). In the study, 207 adultpatients with a confirmed inadequate response to existing first-lineSSRI or SNRI therapy for MDD received adjunctive treatment of either 34mg pimavanserin or placebo in addition to pre-existing first-linetherapy for five weeks (Stage 1). Those patients who did not show aresponse to placebo in Stage 1 were re-randomized to receive eitherpimavanserin or placebo for a second five-week treatment period (Stage2).

In the trial, pimavanserin met the overall primary endpoint of theweighted average results of Stage 1 and Stage 2 by significantlyreducing 17-item Hamilton Depression Rating Scale (HAMD-17) total scorecompared to placebo (p=0.039). In addition, in Stage 1 (n=207) patientson pimavanserin demonstrated a highly significant improvement in HAMD-17(p=0.0003). Importantly, this group of patients saw a benefit overplacebo in the first week of treatment (p=0.0365). Stage 2 (n=58)results did not demonstrate significant separation in this small set ofplacebo non-responders.

On the key secondary endpoint, pimavanserin demonstrated statisticallysignificant reductions compared to placebo in the Sheehan DisabilityScale (SDS) score (p=0.004).

Positive results were also observed for seven of the eleven othersecondary endpoints listed below with nominal p-values: Clinical GlobalImpression-Severity (p=0.0084), Clinical Global Impression-Improvement(p=0.0289), Short Form-12 Mental Component Summary (p<0.0001),Karolinska Sleepiness Scale (p=0.0205), Massachusetts General HospitalSexual Functioning Index (p=0.0003), Barratt Impulsiveness Scale(p=0.0075), as well as response rates (p=0.0065), defined as a 50% orgreater reduction on the HAMD-17 total score.

In this Phase 2 study, pimavanserin was generally well-tolerated.Discontinuations due to adverse events were 1.2% for pimavanserin and3.2% for placebo. One subject in each of the pimavanserin and placebogroups reported serious adverse events (SAEs). These SAEs were deemednot to be related to the study drug by the investigators and bothsubjects completed the study. No deaths were reported in the study.

“We are pleased with the robustness of the data from our Phase 2 CLARITYtrial, which shows significant promise for patients with MDD, includingearly and sustained antidepressant response over placebo, decreaseddaytime sleepiness, no meaningful weight gain, and improved sexualfunction. This is important because most people with MDD do not respondto initial antidepressant therapies and experience significant unwantedside effects,” said Serge Stankovic, M.D., M.S.P.H., ACADIA's ExecutiveVice President, Head of Research & Development. “Pimavanserin is aselective serotonin inverse agonist, or SSIA, that shows great potentialas an antidepressant. We look forward to engaging with the FDA andinitiating a Phase 3 program in the first half of 2019.”

“The results of this study suggest pimavanserin may represent a novelapproach to adjunctive treatment for patients suffering from majordepressive disorder. The selective serotonergic mechanism of action mayprovide additional benefit for patients who do not adequately respond toSSRI or SNRI treatment,” said Professor Maurizio Fava, M.D., ExecutiveVice Chair, Department of Psychiatry, Massachusetts General Hospital(MGH) and Associate Dean for Clinical & Translational Research, HarvardMedical School. “The majority of patients with MDD do not respondadequately to initial antidepressant therapy and the treatment effectseen in this study combined with a favorable tolerability profileprovides evidence that adjunctive therapy with pimavanserin may benefitpatients suffering from inadequate response in major depressivedisorder.”

About CLARITY
CLARITY was a Phase 2, 10-week, randomized,double-blind, placebo-controlled, multi-center, 2-stage sequentialparallel comparison design (SPCD) 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 aselective serotonin reuptake inhibitor (SSRI) or a serotoninnorepinephrine reuptake inhibitor (SNRI). The study was conducted incollaboration with the MGH Clinical Trials Network & Institute (CTNI)and randomized 207 patients across 28 clinical research centers in theUnited States.

Consistent with the SPCD design, the study was conducted in two,five-week sequential stages. Eligible subjects continued receiving theirSSRI or SNRI antidepressant at a stable dose for the duration of thestudy. Patients were randomly assigned (1:3) to pimavanserin 34 mg/dayor placebo in Stage 1. Placebo non-responders in Stage 1 (defined asHAMD-17 total score >14 and a percent-reduction from baseline in HAMD-17total score of <50% at week 5) were re-randomized (1:1) to Stage 2 toreceive pimavanserin 34 mg/day or placebo. The primary endpoint of thestudy was the change in HAMD-17 total score for Stage 1 and Stage 2.Treatment differences from Stage 1 and Stage 2 were combined as weightedaverages.

A post-hoc comparison between pimavanserin (n=51) and placebo (n=123)for patients consistently receiving either placebo or pimavanserin forthe entire 10-week period also yielded meaningful separation withpositive p-values at all weeks starting from week 2 to week 10 in favorof pimavanserin for both the primary endpoint, HAMD-17 (week 10,p=0.0076), and the key secondary endpoint, SDS (week 10, p=0.0094).

Conference Call and Webcast Information
ACADIA will discusstop-line results from its Phase 2 trial of pimavanserin for adjunctivetreatment of patients with major depressive disorder via conference calland webcast today at 8:30 a.m. Eastern Time. The conference call can beaccessed by dialing 855-638-4820 for participants in the U.S. or Canadaand 443-877-4067 for international callers (reference passcode 8786247).A telephone replay of the conference call may be accessed throughNovember 30, 2018 by dialing 855-859-2056 for callers in the U.S. orCanada and 404-537-3406 for international callers (reference passcode8786247). The conference call will also be webcast live on ACADIA’swebsite, www.acadia-pharm.com,in the investors section and archived until November 30, 2018.

About Major Depressive Disorder (MDD)
According to theNational Institute of Mental Health, MDD affects approximately 16million adults in the United States¹, with approximately 2.5million adults treated with adjunctive therapy^2,3. MDD is acondition characterized by depressive symptoms, such as a depressed moodor a loss of interest or pleasure in daily activities for more than twoweeks, as well as impaired social, occupational or other importantfunctioning. The majority of people who suffer from MDD do not respondadequately to initial antidepressant therapy⁴.

About Pimavanserin
Pimavanserin is a selective serotonininverse agonist (SSIA) 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 (34 mg) was approved for the treatment of hallucinationsand delusions associated with Parkinson’s disease psychosis by the U.S.Food and 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 is commercializing the first andonly medicine approved for the treatment of hallucinations and delusionsassociated with Parkinson’s disease psychosis. In addition, ACADIA hasongoing clinical development efforts in additional areas withsignificant unmet need, including dementia-related psychosis,schizophrenia inadequate response, schizophrenia-negative symptoms,major depressive disorder, and Rett syndrome. This press release andfurther information about ACADIA 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, 2017 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).

Source: ACADIA Pharmaceuticals Inc.

Investor Contact:

ACADIA Pharmaceuticals Inc.
ElenaRidloff, CFA
(858) 558-2871
ir@acadia-pharm.com
or
MediaContact:
ACADIA Pharmaceuticals Inc.
Maurissa Messier
(858)768-6068
media@acadia-pharm.com