Allergan Receives Refusal to File Letter from FDA for Vraylar® (cariprazine) Supplemental New Drug Application (sNDA) for the Treatment of Negative Symptoms in Schizophrenia

DUBLIN, Sept. 22, 2017 /PRNewswire/ -- Allergan plc (NYSE: AGN) today announced that it received a Refusal to File (RTF) letter from the U.S. Food and Drug Administration (FDA) regarding its Supplemental New Drug Application (sNDA) for Vraylar (cariprazine) for treatment of negative symptoms associated with schizophrenia in adult patients. VRAYLAR is an oral, once daily atypical antipsychotic approved in the United States for the treatment of schizophrenia and the acute treatment of adult patients with manic or mixed episodes associated with bipolar I disorder.

Upon its preliminary review, FDA determined that the sNDA for treatment of negative symptoms was not sufficiently complete to permit a substantive review.  

"We are disappointed with the FDA decision on our submission. We will request a meeting with FDA to discuss and determine our next steps. Vraylar is an important treatment option for patients suffering from bipolar I disorder and schizophrenia. We remain committed to our mental health program and to cariprazine and its potential as a treatment option for patients suffering from negative symptoms associated with schizophrenia," said David Nicholson Ph.D., Chief Research & Development Officer, Allergan.   

Schizophrenia is a chronic and disabling disorder that includes positive symptoms (i.e. hallucinations, delusions and thought disorders) and negative symptoms (i.e. loss of motivation and social withdrawal). These symptoms are strongly associated with long term morbidity, poor psychosocial functioning and considerable social and economic costs.

Cariprazine is approved in Europe for the treatment of schizophrenia. The approval includes data from the 460-patient negative symptoms study which was conducted by Gedeon Richter and published in the Lancet on February 6, 2017.

The Company will seek immediate guidance, and is in the process of planning a meeting with the FDA, to respond to the issues, and to seek clarification of what additional information will be required.

About VRAYLAR (cariprazine)

VRAYLAR is an oral, once daily atypical antipsychotic approved for the acute treatment of adult patients with manic or mixed episodes associated with bipolar I disorder, with a recommended dose range of 3 to 6 mg/day, and for the treatment of schizophrenia in adults, with a recommended dose range of 1.5 to 6 mg/day.

While the mechanism of action of VRAYLAR in schizophrenia and bipolar I disorder is unknown, the efficacy of VRAYLAR could be mediated through a combination of partial agonist activity at central dopamine D₂ and serotonin 5-HT_1A receptors and antagonist activity at serotonin 5-HT_2A receptors.

Pharmacodynamic studies with cariprazine have shown that it acts as a partial agonist at dopamine D₃, dopamine D₂, and with high binding affinity at the serotonin 5-HT_1A. Cariprazine demonstrated up to ~8-fold greater in vitro affinity for dopamine D₃ vs D₂ receptors. Cariprazine also acts as an antagonist at serotonin 5-HT_2B and 5-HT_2A receptors with high and moderate binding affinity, respectively as well as it binds to the histamine H₁ receptors. Cariprazine shows lower binding affinity to the serotonin 5-HT_2C and α_1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors. The clinical significance of these in vitro data is unknown.

VRAYLAR was discovered and co-developed by Gedeon Richter Plc and is licensed to Allergan in the U.S. and Canada.

Visit www.VRAYLAR.com for more information on this once daily option for the acute treatment of manic or mixed episodes associated with bipolar I disorder and for the treatment of schizophrenia in adults.

About Allergan plc

Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical company and a leader in a new industry model – Growth Pharma. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world.

Allergan markets a portfolio of leading brands and best-in-class products for the central nervous system, eye care, medical aesthetics and dermatology, gastroenterology, women's health, urology and anti-infective therapeutic categories.

Allergan is an industry leader in Open Science, a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry with 65+ mid-to-late stage pipeline programs currently in development.

Allergan's success is powered by our more than 18,000 global colleagues' commitment to being Bold for Life. Together, we build bridges, power ideas, act fast and drive results for our customers and patients around the world by always doing what is right.

With commercial operations in approximately 100 countries, Allergan is committed to working with physicians, healthcare providers and patients to deliver innovative and meaningful treatments that help people around the world live longer, healthier lives every day.

For more information, visit Allergan's website at www.Allergan.com.

Forward-Looking Statement

Statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Allergan's current perspective on existing trends and information as of the date of this release. Actual results may differ materially from Allergan's current expectations depending upon a number of factors affecting Allergan's business. These factors include, among others, the difficulty of predicting the timing or outcome of FDA approvals or actions, if any; the impact of competitive products and pricing; market acceptance of and continued demand for Allergan's products; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Allergan's periodic public filings with the Securities and Exchange Commission, including but not limited to Allergan's Annual Report on Form 10-K for the year ended December 31, 2016 and Allergan's Quarterly Report on Form 10-Q for the period ended June 30, 2017. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.

CONTACTS:      

Allergan:
Investors:
Daphne Karydas
(862) 261-8006

Media:
Mark Marmur
(862) 261-7558

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SOURCE Allergan plc