Acadia Pharmaceuticals Receives Complete Response Letter from U.S. FDA for Supplemental New Drug Application for Pimavanserin for the Treatment of Hallucinations and Delusions Associated with Alzheimer’s Disease Psychosis
The CRL indicated that the FDA has completed review of the application, determining that it could not approve the sNDA in its present form, and recommended that Acadia conduct an additional trial in ADP. While the FDA stated that Study 019 demonstrated a statistically significant treatment effect on its primary endpoint, they concluded that there are limitations in the interpretability of the 019 results. The FDA also stated that the positive treatment effect of pimavanserin on dementia-related psychosis in Study 045 (HARMONY) appeared to be driven by the robustly positive results in the Parkinson’s disease dementia subgroup, a condition they stated is subsumed within the currently approved NUPLAZID Parkinson’s disease psychosis (PDP) indication. Up to 50 percent of PDP patients have dementia.1
“We are disappointed with this outcome. The treatment of Alzheimer’s disease psychosis continues to be an area of high unmet need, for which there is no approved therapy,” said
NUPLAZID was approved in the
About Alzheimer’s Disease Psychosis
According to the Alzheimer’s Association, approximately six million people in
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
Acadia is advancing 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’s disease psychosis. Our late-stage development efforts are focused on the negative symptoms of schizophrenia and Rett syndrome. Our early-stage development efforts are focused on novel approaches to pain management, cognition and neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at www.acadia.com and follow us on LinkedIn and Twitter.
Important Safety Information
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-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.
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 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 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%).
- 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.
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 read the full Prescribing Information including Boxed WARNING.
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
1 Holt RJ et al. Prevalence of Parkinson’s disease-induced psychosis in a large
2 Alzheimer’s Association. 2021 Alzheimer’s Disease Facts and Figures. Alzheimer’s Dement. 2021; 16(3): 391.
3 Rajan KB et al. Population estimate of people with clinical Alzheimer’s disease and mild cognitive impairment in
4 Cummings J et al. Criteria for Psychosis in Major and Mild Neurocognitive Disorders: International Psychogeriatric Associations (IPA) Consensus Clinical and Research Definition. Am J of Geriatric Psychiatry. 2020; 28(12): 1256-1269.
5 Ballard C et al. A prospective study of psychotic symptoms in dementia sufferers: psychosis in dementia. Int Psychogeriatr. 1997; 9(1): 57-64.
6 Scarmeas N et al. Delusions and hallucinations are associated with worse outcome in Alzheimer Disease. Arch Neurol. 2005; 62(10): 1601-1608.
7 Peters ME et al. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer’s dementia and death: the Cache County Dementia Progression study. Am J Psychiatry. 2015; 172(5): 460-465.