ACADIA Pharmaceuticals Announces that The Journal of Clinical Psychiatry Publishes Positive Phase 2 CLARITY Results for Pimavanserin as Adjunctive Treatment for Patients with Major Depressive Disorder

ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD), announced today that positive results from the Phase 2 CLARITY study evaluating pimavanserin as adjunctive treatment in patients with major depressive disorder (MDD) have been published online by The Journal of Clinical Psychiatry, the official journal of the American Society of Clinical Psychopharmacology (ASCP). In this 10-week, randomized, double-blind, placebo-controlled study (n=207), pimavanserin met the overall primary endpoint of the study by significantly reducing the 17-item Hamilton Depression Rating Scale (HAMD-17) total score compared to placebo (p=0.039). In the parallel design portion (Stage 1) of this two-stage sequential parallel comparison design (SPCD) study, adding pimavanserin to first-line SSRI or SNRI therapy also significantly reduced HAMD-17 scores compared to placebo (p=0.0003). On the key secondary endpoint, pimavanserin also demonstrated statistically significant reductions compared to placebo in the Sheehan Disability Scale (SDS) score (p=0.004).

The study published today, “A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients with Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY),” also included positive overall results observed for additional secondary study endpoints with nominal p-values including: Clinical Global Impression-Severity (p=0.0084), Clinical Global Impression-Improvement (p=0.0289), Karolinska Sleepiness Scale (p=0.0205), Massachusetts General Hospital Sexual Functioning Index (p=0.0003), and Barratt Impulsiveness Scale (p=0.0075). Pimavanserin was well-tolerated in the study and the most common adverse events reported in the pimavanserin group were dry mouth, nausea, and headache all with frequency of less than 10%.

“Today, the standard of care in MDD is to start patients on SSRI or SNRI therapies. However, a majority of patients do not adequately respond to these initial treatments and are prescribed an adjunctive therapy to manage their symptoms,” said Professor Maurizio Fava, M.D., Executive Vice Chair, Department of Psychiatry, Massachusetts General Hospital (MGH) and Associate Dean for Clinical & Translational Research, Harvard Medical School. “Results from this study suggest pimavanserin could be an important new adjunctive treatment for MDD patients who continue to experience significant depression with their initial therapy.”

“Based on these positive Phase 2 results, we initiated our Phase 3 CLARITY program earlier this year to further evaluate pimavanserin as an adjunctive treatment option for MDD. At least one additional positive trial out of the two ongoing Phase 3 studies, together with our Phase 2 study, will serve as the basis for an sNDA submission,” said Serge Stankovic, M.D., M.S.P.H., ACADIA's President.

About the Phase 2 CLARITY Study

The study was conducted in collaboration with the MGH Clinical Trials Network & Institute (CTNI) and randomized 207 adult patients with a confirmed inadequate response to existing first-line selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) therapy for MDD across 27 U.S. clinical research centers.

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

About Major Depressive Disorder

According to the National Institute of Mental Health, MDD affects approximately 16 million adults in the U.S.1, with approximately 2.5 million adults treated with adjunctive therapy.2,3 MDD is a condition characterized by depressive symptoms such as a depressed mood or a loss of interest or pleasure in daily activities for more than two weeks, as well as impaired social, occupational, or other important functioning. The majority of people who suffer from MDD do not respond adequately to initial antidepressant therapy.4

About Pimavanserin

Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors. ACADIA is evaluating pimavanserin in an extensive clinical development program across multiple indications with significant unmet need including dementia-related psychosis, adjunctive major depressive disorder, and the negative symptoms of schizophrenia. Pimavanserin was approved for the treatment of hallucinations and 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 dementia-related psychosis, schizophrenia or major depressive disorder.

About ACADIA Pharmaceuticals

ACADIA is a biopharmaceutical company focused on the development and commercialization of innovative medicines to address unmet medical needs in central nervous system disorders. ACADIA has developed and commercialized the first and only medicine approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. ACADIA also has ongoing clinical development efforts in additional areas with significant unmet need, including dementia-related psychosis, major depressive disorder, the negative symptoms of schizophrenia, and Rett syndrome. This press release and further information about ACADIA can be found at: www.acadia-pharm.com.

Forward-Looking Statements

Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements include, but are not limited to, statements related to: the potential benefits of pimavanserin as adjunctive treatment for major depressive disorder or other central nervous system disorders as well as the potential results of clinical trials of pimavanserin in other indications. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in drug development, approval and commercialization, and the fact that past results of clinical trials may not be indicative of future trial results. For a discussion of these and other factors, please refer to ACADIA’s annual report on Form 10-K for the year ended December 31, 2018 as well as ACADIA’s subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and ACADIA undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law.

Important Safety Information and Indication for NUPLAZID (pimavanserin)

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

• NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.

• Contraindication: NUPLAZID is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. 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.
  • The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.
  • NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation 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:
  • Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to 10 mg taken orally as one tablet once daily.
  • Coadministration with strong or moderate CYP3A4 inducers reduces NUPLAZID exposure. Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID.

Indication: NUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.

Dosage and Administration: Recommended dose: 34 mg capsule taken orally once daily, without titration.

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

Please see the full Prescribing Information including Boxed WARNING for NUPLAZID.

References

1National Institute of Mental Health. (2017). Major Depression. 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 Depression Episodes 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).

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