\nAcadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the Company has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its supplemental New Drug Application (sNDA) for NUPLAZID\u00ae <\/sup>(pimavanserin) for the treatment of hallucinations and delusions associated with dementia-related psychosis (DRP). The FDA issued a CRL to indicate that they have completed their review of the application and has determined that the application cannot be approved in its present form.\n<\/p>\n
\nDespite prior agreements with the Division of Psychiatry regarding the pivotal Phase 3 HARMONY study design targeting a broad DRP patient population analyzed as a single group, the Division, in the CRL, cited a lack of statistical significance in some of the subgroups of dementia, and insufficient numbers of patients with certain less common dementia subtypes as lack of substantial evidence of effectiveness to support approval.\n<\/p>\n
\nThe DRP pivotal HARMONY study met its prespecified primary and secondary endpoints with robust and persuasive clinical and statistical superiority of pimavanserin over placebo, which was a prospectively agreed prerequisite for the DRP indication. Statistical separation by dementia subgroups and certain minimum numbers of patients with specific subtypes were not among the prespecified requirements.\n<\/p>\n
\n\u201cAcadia stands behind the robustly positive results from the pivotal Phase 3 HARMONY study and the prospectively agreed trial design and criteria for establishing efficacy in DRP. Over the entire course of the review, the Division did not raise any concerns regarding the agreed upon study design, including the issues raised in the CRL,\u201d said Steve Davis, Chief Executive Officer of Acadia. \u201cWe will immediately request a Type A meeting to work with the FDA to address the CRL and determine an expeditious path forward for the approval of pimavanserin in DRP.\u201d\n<\/p>\n
\nThe Division also stated in the CRL that it considers the Phase 2 Alzheimer\u2019s disease psychosis study -019, a supportive study in the sNDA filing, to not be adequate and well controlled, citing that it was a single center study with no type I error control of secondary endpoints in which certain protocol deviations occurred. The Company believes these observations impact neither the positive results on the study\u2019s primary endpoint, nor the study\u2019s overall conclusions of efficacy.\n<\/p>\n
\nThere were no safety issues or concerns raised in the CRL.\n<\/p>\n
sNDA Submission for Dementia-Related Psychosis<\/b><\/p>\n
\nThe sNDA submission of pimavanserin for the treatment of hallucinations and delusions associated with DRP was supported by results from the pivotal Phase 3 HARMONY study, which met its primary endpoint, demonstrating that pimavanserin significantly reduced the risk of relapse of psychosis by 2.8 fold compared to placebo (hazard ratio = 0.353; one-sided p=0.0023). Pimavanserin also met the key secondary endpoint in the study, significantly reducing the risk of discontinuation for any reason by 2.2 fold compared to placebo (hazard ratio = 0.452, one-sided p=0.0024). The sNDA also included positive efficacy results from two additional placebo-controlled studies, both of which met their respective primary endpoints: the Phase 2 (-019) study in patients with Alzheimer\u2019s disease psychosis and the Phase 3 (-020) study in patients with Parkinson\u2019s disease psychosis. In addition, the sNDA included a large safety database from completed and ongoing studies representing over 1,500 patients with neurodegenerative disease.\n<\/p>\n
Conference Call and Webcast Information<\/i><\/p>\n
\nAcadia management will discuss today\u2019s announcement via conference call and webcast at 8:00 a.m. Eastern Time. The conference call may be accessed by dialing 855-638-4820 for participants in the United States or Canada and 443-877-4067 for international callers (reference passcode 6894834). A telephone replay of the conference call may be accessed through April 19, 2021 by dialing 855-859-2056 for callers in the United States or Canada and 404-537-3406 for international callers (reference passcode 6894834). The conference call also will be webcast live on Acadia\u2019s website, www.acadia-pharm.com<\/a> under the investors section and will be archived there through May 3, 2021.\n<\/p>\n About Dementia-Related Psychosis<\/i><\/p>\n \nApproximately 8 million people in the United States are living with dementia, a condition with a core feature of declining cognition (changes in memory, decision-making abilities, language, etc.) resulting in functional impairment. Dementia is a manifestation of an underlying condition which is often progressive and neurodegenerative in nature. In addition to cognitive decline, dementing illnesses almost universally lead to neuropsychiatric symptoms, including hallucinations, delusions, and changes in behavior.\n<\/p>\n \nIt is estimated that 2.4 million Americans (or 30% of people with dementia) experience dementia-related hallucinations and delusions. These symptoms may be frequent and severe and may recur over time. A hallucination is defined as a perception-like experience that occurs without an external stimulus and is sensory (seen, heard, felt, tasted, sensed) in nature. A delusion is defined as a false, fixed belief that is resolutely held despite evidence to the contrary. Dementia-related psychosis occurs in many types of dementia, including Alzheimer\u2019s disease, dementia with Lewy bodies, Parkinson\u2019s disease dementia, vascular dementia, and frontotemporal dementia. Serious consequences have been associated with psychosis in patients with dementia, such as repeated hospital admissions, increased likelihood of nursing home placement, faster progression of dementia, and increased risk of morbidity and mortality.\n<\/p>\n About Pimavanserin<\/i><\/p>\n \nPimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A<\/sub> receptors. These receptors are thought to play an important role in neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors. Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson\u2019s disease psychosis by the U.S. Food and Drug Administration in April 2016 under the trade name NUPLAZID\u00ae<\/sup>. NUPLAZID is not approved for dementia-related psychosis. In addition, Acadia is developing pimavanserin in other neuropsychiatric conditions.\n<\/p>\n About Acadia Pharmaceuticals<\/i><\/p>\n \nAcadia is trailblazing breakthroughs in neuroscience to elevate life. For more than 25 years we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only approved therapy for hallucinations and delusions associated with Parkinson\u2019s disease psychosis. Our late-stage development efforts are focused on dementia-related psychosis, negative symptoms of schizophrenia and Rett syndrome, and in early-stage clinical research we are exploring novel approaches to pain management, and cognition and neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at www.acadia-pharm.com<\/a> and follow us on LinkedIn<\/a>.\n<\/p>\n Forward-Looking Statements<\/i><\/p>\n \nStatements in this press release that are not strictly historical in nature are forward-looking statements. These statements include but are not limited to statements regarding the timing of future events. 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. For a discussion of these and other factors, please refer to Acadia\u2019s annual report on Form 10-K for the year ended December 31, 2020 as well as Acadia\u2019s 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.\n<\/p>\n Important Safety Information and Indication for NUPLAZID\u00ae<\/sup> (pimavanserin)<\/b><\/p>\n Indication<\/b><\/p>\n \nNUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson\u2019s disease psychosis.\n<\/p>\n Important Safety Information<\/b><\/p>\n WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS<\/b><\/p>\n \n\u2022\n<\/p>\n<\/td>\n Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.<\/b><\/p>\n<\/td>\n<\/tr>\n \n\u2022\n<\/p>\n<\/td>\n NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson\u2019s disease psychosis.<\/b><\/p>\n<\/td>\n<\/tr>\n \n\u00a0\n<\/p>\n<\/td>\n<\/tr>\n \n\u2022\n<\/p>\n<\/td>\n \n\u00a0\n<\/p>\n<\/td>\n<\/tr>\n \n\u2022\n<\/p>\n<\/td>\n \n\u00b0\n<\/p>\n<\/td>\n \nNUPLAZID 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.\n<\/p>\n<\/td>\n<\/tr>\n \n\u00b0\n<\/p>\n<\/td>\n \nNUPLAZID 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.\n<\/p>\n<\/td>\n<\/tr>\n \n\u00a0\n<\/p>\n<\/td>\n<\/tr>\n \n\u2022\n<\/p>\n<\/td>\n \n\u00a0\n<\/p>\n<\/td>\n<\/tr>\n \n\u2022\n<\/p>\n<\/td>\n \n\u00b0\n<\/p>\n<\/td>\n \nCoadministration with strong CYP3A4 inhibitors (e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to 10 mg taken orally as one tablet once daily.\n<\/p>\n<\/td>\n<\/tr>\n \n\u00b0\n<\/p>\n<\/td>\n \nCoadministration with strong or moderate CYP3A4 inducers reduces NUPLAZID exposure. Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID.\n<\/p>\n<\/td>\n<\/tr>\n<\/table>\n Dosage and Administration<\/b><\/p>\n \nRecommended dose: 34 mg capsule taken orally once daily, without titration.\n<\/p>\n \nNUPLAZID is available as 34 mg capsules and 10 mg tablets.\n<\/p>\n \nPlease read the full Prescribing Information<\/a> including Boxed WARNING.\n<\/p>\n View source version on businesswire.com: <\/span>https:\/\/www.businesswire.com\/news\/home\/20210405005229\/en\/<\/a><\/span><\/p>\n Media Contact: Investor Contact: KEYWORDS:<\/b> California United States North America<\/p>\n INDUSTRY KEYWORDS:<\/b> Mental Health FDA Health Clinical Trials Pharmaceutical Biotechnology<\/p>\n\n
\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Contraindication:<\/b> 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.<\/td>\n<\/tr>\n \n \n \n \n \n \n \n \n \n Warnings and Precautions:<\/b> QT Interval Prolongation<\/td>\n<\/tr>\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Adverse Reactions:<\/b> The common adverse reactions (\u22652% 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%).<\/td>\n<\/tr>\n \n \n \n \n \n \n \n \n \n Drug Interactions:<\/b><\/td>\n<\/tr>\n \n \n \n \n \n \n \n \n \n \n \n \n <\/p>\n
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Acadia Pharmaceuticals Inc.
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Stephanie Fagan
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(858) 212-0534
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media@acadia-pharm.com
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Acadia Pharmaceuticals Inc.
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Mark Johnson, CFA
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(858) 261-2771
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ir@acadia-pharm.com<\/a><\/p>\n
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