Acadia Pharmaceuticals Announces Label Update for NUPLAZID® (pimavanserin)
— U.S. FDA revises Boxed Warning to clarify that NUPLAZID can be used to treat patients with Parkinson’s disease-related hallucinations and delusions who also have dementia
SAN DIEGO — September 18, 2023 – Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the U.S. Food and Drug Administration (FDA) has made two changes to the NUPLAZID label that clarify its use in patients with Parkinson’s disease-related hallucinations and delusions, with or without dementia. This update is consistent with the current indication. There are no other findings or changes included as part of the label change.
The two changes include: 1) Updated language in the Clinical Studies section, that restates that the Phase 3 study supporting the approval of NUPLAZID included patients with Parkinson’s disease-related hallucinations and delusions, with or without dementia; and 2) Revised Boxed Warning language clarifying that NUPLAZID is approved to treat patients with Parkinson’s disease-related hallucinations and delusions who also have dementia. The risk information in the Boxed Warning has not changed. See important safety information below for updates to the Boxed Warning.
“This update makes it clear that NUPLAZID can be prescribed to treat patients with Parkinson’s disease psychosis, with or without dementia,” said Jeffrey Cummings, M.D., Sc.D, Director of the Chambers-Grundy Center for Transformative Neuroscience, University of Nevada, Las Vegas. “As a prescriber, I believe that this clarification to the Boxed Warning language will help healthcare providers better identify appropriate candidates with Parkinson’s disease psychosis for treatment with NUPLAZID.”
About Parkinson’s Disease and Parkinson’s Disease Psychosis
Parkinson’s disease is a progressive nervous system disorder that affects about one million people in the United States.1,2 The signs and symptoms can vary with people experiencing both motor symptoms and non-motor symptoms such as hallucinations (seeing, hearing, or experiencing things that others don’t) and delusions (false beliefs).3,4 Physicians may refer to these Parkinson’s-related hallucinations and delusions as Parkinson’s disease psychosis.3 Around 50 percent of people living with Parkinson’s may experience hallucinations or delusions during the course of their disease.4 Non-motor symptoms, as a whole, can be more troublesome than motor symptoms, in terms of quality of life.5 Parkinson’s disease psychosis may add to the burden of caring for a loved one with Parkinson’s disease.6,7
Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A 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’s disease psychosis by the U.S. Food and Drug Administration in April 2016 under the trade name NUPLAZID. In addition, Acadia is developing pimavanserin in other neuropsychiatric conditions.
Indication and Important Safety Information for NUPLAZID® (pimavanserin)
NUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
Important Safety Information
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 who experience psychosis unless their hallucinations and delusions are related to Parkinson’s disease. (Emphasis added to clarify updated text.)
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.
Warnings and Precautions: 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 (e.g., Class 1A antiarrhythmics, Class 3 antiarrhythmics, certain antipsychotics or 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 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%).
Coadministration with strong CYP3A4 inhibitors 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.
Dosage and Administration
Recommended dose: 34 mg capsule taken orally once daily, without titration, with or without food.
NUPLAZID is available as 34 mg capsules and 10 mg tablets.
Please read the full Prescribing Information including Boxed WARNING.
About Acadia Pharmaceuticals
Acadia is advancing breakthroughs in neuroscience to elevate life. For 30 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 therapies for hallucinations and delusions associated with Parkinson’s disease psychosis and for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on treating the negative symptoms of schizophrenia, Prader-Willi syndrome, Alzheimer’s disease psychosis and neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at www.acadia.com and follow us on LinkedIn and Twitter.
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 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’s annual report on Form 10-K for the year ended December 31, 2022, 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.
1Parkinson’s Disease Foundation. What is Parkinson’s disease? Retrieved from https://www.parkinson.org/Understanding-Parkinsons/Statistics. Accessed August 2023.
2Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591-1601.
3Ravina B, Marder K, Fernandez HH, et al. Diagnostic criteria for psychosis in Parkinson’s disease: report of an NINDS, NIMH work group. Mov Disord. 2007 Jun 15;22(8):1061-8
4Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson’s disease. Arch Neurol. 2010;67(8):996-1001.
5Martinez-Martin P, Rodriguez-Blazquez C, et al. The Impact of Non-Motor Symptoms on Health Related Quality of Life of Patients with Parkinson’s Disease. Mov Disord. 2011;26(3):399-406.
6Schrag A, Hovris A, et al. Caregiver-burden in parkinson’s disease is closely associated with psychiatric symptoms, falls, and disability. Parkinsonism and Related Disorders. 2006;12:35-41.
7Aarsland D, Bronnick K, Ehrt U. et al. Neuropsychiatric symptoms in patients with Parkinson’s disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatry. 2007;78:36-42.