Allergan and Gedeon Richter Plc. to Present Data on Cariprazine at the American Psychiatric Association (APA) Annual Meeting

DUBLIN and BUDAPEST, Hungary, May 12, 2016 /PRNewswire/ -- Allergan plc (NYSE: AGN) and Gedeon Richter Plc. today announced that nine posters highlighting additional scientific data and clinical research on cariprazine, an atypical antipsychotic, will be presented during the upcoming American Psychiatric Association Annual Meeting in Atlanta, GA, May 14 to May 18, 2016.

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"Advancing scientific discovery and addressing unmet clinical needs are at the heart of Allergan's Open Science approach," said Dr. David Nicholson, President & Executive Vice President, Global R&D at Allergan. "The abstracts presented at APA underscore the safety and efficacy of cariprazine, and investigated its potential to provide additional therapeutic benefits for the treatment of bipolar depression and the negative symptoms of schizophrenia."

The titles of the poster presentations are as follows:

Monday, May 16, 2016, 2:00-4:00 p.m. ET

• Relationship of Cariprazine Plasma Concentration to Efficacy and Safety in Patients with Schizophrenia or Bipolar Mania (P6-014), authored by Carrothers, T., Willavize, S., Jaworowicz, D., Passarell, J., Periclou, A., Ghahramani, P., Durgam, S., Earley, W., Kapás, M., Khariton, T.

Tuesday, May 17, 2016, 2:00-4:00 p.m. ET

• Efficacy of Cariprazine on Predominant Negative Symptoms of Patients with Schizophrenia: Post Hoc Analysis of PANSS data, Marder Factors and Cognition (P8-081), authored by Marder, S., Laszlovszky, I., Szalai, E., Szatmári, B., Harsányi, J., Barabássy, A., Debelle, M., Durgam, S., Bitter, I., Németh, G.

• Efficacy of Cariprazine in Negative, Cognitive, and Social Function Symptoms in Schizophrenia: Post Hoc Analysis of a Randomized, Controlled Trial (P8-022), authored by Cutler, A., Durgam, S., Lu, K., Laszlovszky, I., Earley, W.

• Early Improvement is a Predictor of Response and Remission in Bipolar I Disorder: A Pooled Analysis of 3 Randomized Cariprazine Trials (P8-026), authored by Durgam, S., Calabrese, J., Earley, W., Migliore, R., Lu, K., Laszlovszky, I.

• Safety and Efficacy of Cariprazine in FDA-Approved Dose Ranges for Schizophrenia and Bipolar I Disorder: A Pooled Post Hoc Analysis (P8-027), authored by Earley, W., Durgam, S., Lu, K., Németh, G., Laszlovszky, I.

• Long-Term Cariprazine Treatment for the Prevention of Relapse in Patients With Schizophrenia: Analysis of Additional Efficacy Outcomes (P8-095), authored by Nasrallah, H., Durgam, S., Earley, W., Lu, K., Laszlovszky, I.

• Efficacy of Cariprazine in Bipolar Depression: Post Hoc Band-Pass Analyses of 2 Randomized, Double-Blind, Placebo-Controlled Trials (P8-144), authored by Yatham, L., Vieta, E., Durgam, S., Earley, W., Lu, K., Laszlovszky, I.

• Pharmacological Characteristics of Major Human Metabolites of Cariprazine (P8-062), authored by Kiss, B., Némethy, Z., Laszlovszky, I., Gyertyán, I., Adham N.

• Characterization of Population Pharmacokinetics of Cariprazine and Its Major Metabolites (P8-105), authored by Periclou, A., Phillips, L., Bihorel, S., Ghahramani, P., Kapás, M., Carrothers, T., Khariton, T.

About Cariprazine

Cariprazine 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.  

Cariprazine – marketed as VRAYLAR™ in the United States – was approved by the U.S. Food and Drug Administration for the treatment of acute manic or mixed episodes of bipolar I disorder and schizophrenia in adults.

Although the exact mechanism of action for cariprazine is unknown, it is thought to affect the activity of neurotransmitters such as dopamine and serotonin. The efficacy of cariprazine 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 have shown that VRAYLAR (cariprazine) acts as a partial agonist at the dopamine D₃ and dopamine D₂ receptors, with high binding affinity (K_i  values of 0.085 nM, and 0.49 nM (D_2L) and 0.69 nM (D_2S), respectively). Cariprazine demonstrated up to

~8-fold greater in vitro affinity for dopamine D₃ vs D₂ receptors. Cariprazine acts as a partial agonist at serotonin 5-HT_1A receptors (K_i value of 2.6 nM) and as an antagonist at serotonin 5-HT_2B and 5-HT_2A receptors with high and moderate binding affinity (K_i values of 0.58 nM and 18.8 nM, respectively). It also binds to the histamine H₁ receptors (K_i value of 23.2 nM). Cariprazine shows lower binding affinity for the serotonin 5-HT_2C and α_1A-adrenergic receptors (K_i values of 134 nM and155 nM, respectively) and has no appreciable affinity for cholinergic muscarinic receptors (IC₅₀>1000 nM). The clinical significance of these in vitro data is unknown.

Cariprazine 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.

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. VRAYLAR is not approved for treatment of patients with dementia-related psychosis.

Contraindication: VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and events suggestive of angioedema.

Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic drugs, elderly subjects with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities vs placebo. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotics drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.  Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered.

Late-Occurring Adverse Reactions: Adverse events may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. As a result, the incidence of adverse reactions in short-term trials may not reflect the rates after longer term exposures. Monitor for adverse reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug.

Metabolic Changes: Atypical antipsychotics have caused metabolic changes, such as:

• Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Assess fasting glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment.
• Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after starting an antipsychotic, obtain baseline fasting lipid profile and monitor periodically during treatment.
• Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at baseline and frequently thereafter.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases.

Seizures: Use VRAYLAR with caution in patients with history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle).

Body Temperature Dysregulation: Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration.

Drug Interactions: Strong CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended.

Adverse Reactions: In clinical trials, the most common adverse reactions (≥5% and at least twice the rate of placebo) are listed below:

• Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5 – 3 mg/day and 4.5 – 6 mg/day vs placebo) were: EPS (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%)
• Bipolar mania: The incidences within the recommended dose range (VRAYLAR 3 – 6 mg/day vs placebo) were: EPS (26% vs 12%), akathisia (20% vs 5%), dyspepsia (7% vs 4%), vomiting (10% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%)

Please also see full Prescribing Information, including Boxed Warning, at www.vraylar.com.

About Gedeon Richter

Gedeon Richter Plc. (www.richter.hu), headquartered in Budapest/Hungary, is a major pharmaceutical company in Central Eastern Europe, with an expanding direct presence in Western Europe. Having reached a market capitalisation of EUR 3.3 billion (US$ 3.6 billion) by the end of 2015, Richter's consolidated sales were approximately EUR 1.2 billion (US$ 1.3 billion) during the same year. The product portfolio of Richter covers many important therapeutic areas, including gynaecology, central nervous system, and cardiovascular areas. Having the largest R&D unit in Central Eastern Europe, Richter's original research activity focuses on CNS disorders. With its widely acknowledged steroid chemistry expertise, Richter is a significant player in the female healthcare field worldwide. Richter is also active in biosimilar product development.

About Allergan

Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a unique, global pharmaceutical company and a leader in a new industry model – Growth Pharma. Allergan is focused on developing, manufacturing and commercializing innovative branded pharmaceuticals, high-quality generic and over-the-counter medicines and biologic products for patients around the world.

Allergan markets a portfolio of best-in-class products that provide valuable treatments for the central nervous system, eye care, medical aesthetics, gastroenterology, women's health, urology, cardiovascular and anti-infective therapeutic categories, and operates the world's third-largest global generics business, providing patients around the globe with increased access to affordable, high-quality medicines. Allergan is an industry leader in research and development, with one of the broadest development pipelines in the pharmaceutical industry and a leading position in the submission of generic product applications globally.

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.

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 of existing trends and information as of the date of this release. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements. 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 risks associated with acquisition transactions; 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 Quarterly Report on Form 10-Q for the quarter ended December 31, 2015 (such periodic public filings having been filed under the "Actavis plc" name) and from time to time in Allergan's other investor communications . Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.

ALLERGAN CONTACTS:

Investors: 
Lisa DeFrancesco 
(862) 261-7152

Media:  
Mark Marmur 
(862) 261-7558

GEDEON RICHTER CONTACTS:

Investors:
Katalin Ördög 
+36 1 431 5680

Media:
Zsuzsa Beke
+36 1 431 4888

SOURCE Allergan plc

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