– Application Seeks to Expand VRAYLAR Indication to Include the Treatment of Bipolar Depression –
DUBLIN, Ireland I September 26, 2018 I Allergan plc (NYSE: AGN), a leading global pharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the company’s supplemental New Drug Application (sNDA) for VRAYLAR® (cariprazine), seeking to expand the indication to include the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults in the current product label.
The sNDA is supported by data from three pivotal trials, including RGH-MD-53, RGH-MD-54 and RGH-MD-56. In all three pivotal studies, cariprazine demonstrated greater improvement than placebo for the change from baseline to week 6 on the Montgomery Asberg Depression Rating scale (MADRS) total score. Both cariprazine 1.5 mg and 3 mg demonstrated superiority to placebo in reducing depressive symptoms associated with bipolar I depression.
“Despite decades of development, bipolar depression remains difficult to treat. Importantly, bipolar I patients will need treatment for the full spectrum of of their disorder,” said Gary Sachs, MD, Associate Clinical Professor of Psychiatry at Harvard Medical School. “If approved for bipolar depression, cariprazine would be the first and only partial agonist with proven efficacy for both the manic and depressive symptoms of bipolar I disorder. That is very encouraging news for patients, their families, and the psychiatry community.”
Cariprazine was generally well tolerated in the trials. The most commonly reported adverse events (i.e., those reported by ≥ 5% of patients in any cariprazine treatment group and at twice the rate of placebo) were nausea, akathisia, restlessness and upper respiratory tract infection. Adverse events led to discontinuation in 6.7% of cariprazine-treated patients versus 4.8% of placebo treated patients.
“This sNDA filing provides an important step towards the availability of a potential treatment option for the approximately 5 million patients suffering with bipolar I depression. These positive pivotal studies, demonstrated the efficacy and safety of VRAYLAR for the treatment of bipolar depression,” said David Nicholson, Chief Research & Development Officer at Allergan. ” “VRAYLAR is the flagship product of our Psychiatry portfolio and demonstrates Allergan’s commitment to the mental health community.”
Cariprazine was approved by the FDA in September 2015 and is marketed as VRAYLAR® in the US for the treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
About Cariprazine Trials in Bipolar I Depression
The efficacy and safety of cariprazine in bipolar depression was evaluated in a total of four, 6- and 8-week randomized, placebo-controlled studies. One exploratory study phase 2 study RGH-MD-52 in bipolar I & II patients, and 3 pivotal studies (RGH-MD-56, 53 & 54) in bipolar I patients.
RGH MD 52 was a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comparing cariprazine to placebo in outpatients with a primary diagnosis of bipolar I or II disorder who were experiencing a major depressive episode. The study randomized 233 patients with bipolar I and bipolar II disorder to 1 of 3 dose groups for 8 weeks of double blind treatment: cariprazine 0.25 mg to 0.75 mg; cariprazine 1.5 mg to 3 mg; or placebo.
RGH-MD-56 was a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group clinical trial in adult patients with bipolar I depression. A total of 584 patients were randomized to evaluate the efficacy, safety, and tolerability of cariprazine 0.75 mg, 1.5 mg and 3 mg compared to placebo in the treatment of outpatients with bipolar I depression. Patients underwent a no-drug screening period of approximately 7-14 days, followed by 8 weeks of double-blind treatment (primary endpoint was 6-weeks) and a 1-week, no investigational product safety follow-up period.
RGH-MD-53 and RGH-MD-54 were identical Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, fixed-dose clinical trials in adult patients with bipolar I depression. Patients were randomized in both studies aiming to evaluate the efficacy, safety, and tolerability of cariprazine 1.5 mg and 3 mg compared to placebo in outpatients with bipolar I depression. Patients underwent a no-drug screening period of approximately 7-14 days, followed by 6 weeks of double-blind treatment and a 1-week, no investigational product safety follow-up period.
About VRAYLAR® (cariprazine)
VRAYLAR is an oral, once daily atypical antipsychotic approved for the treatment of schizophrenia in adults, with a recommended dose range of 1.5 to 6 mg/day and 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.
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-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. Pharmacodynamic studies with cariprazine have shown that it acts as a partial agonist with high binding affinity at dopamine D3, dopamine D2, and serotonin 5-HT1A receptors. 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-HT2B and 5-HT2A 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-HT2C and α1A– 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 by Allergan, in the U.S. and Canada. For more than a decade both companies have conducted over 20 clinical trials enrolling thousands of patients worldwide to evaluate the efficacy and safety of cariprazine for patients suffering from a broad range of mental health illnesses.
Visit www.vraylar.com for more information.
INDICATION AND USAGE
VRAYLAR (cariprazine) is indicated in adults for the treatment of schizophrenia and for the acute treatment of manic or mixed episodes of bipolar I disorder.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical leader. 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.
Allergan’s success is powered by our 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.
SOURCE: Allergan
Post Views: 143
– Application Seeks to Expand VRAYLAR Indication to Include the Treatment of Bipolar Depression –
DUBLIN, Ireland I September 26, 2018 I Allergan plc (NYSE: AGN), a leading global pharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the company’s supplemental New Drug Application (sNDA) for VRAYLAR® (cariprazine), seeking to expand the indication to include the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults in the current product label.
The sNDA is supported by data from three pivotal trials, including RGH-MD-53, RGH-MD-54 and RGH-MD-56. In all three pivotal studies, cariprazine demonstrated greater improvement than placebo for the change from baseline to week 6 on the Montgomery Asberg Depression Rating scale (MADRS) total score. Both cariprazine 1.5 mg and 3 mg demonstrated superiority to placebo in reducing depressive symptoms associated with bipolar I depression.
“Despite decades of development, bipolar depression remains difficult to treat. Importantly, bipolar I patients will need treatment for the full spectrum of of their disorder,” said Gary Sachs, MD, Associate Clinical Professor of Psychiatry at Harvard Medical School. “If approved for bipolar depression, cariprazine would be the first and only partial agonist with proven efficacy for both the manic and depressive symptoms of bipolar I disorder. That is very encouraging news for patients, their families, and the psychiatry community.”
Cariprazine was generally well tolerated in the trials. The most commonly reported adverse events (i.e., those reported by ≥ 5% of patients in any cariprazine treatment group and at twice the rate of placebo) were nausea, akathisia, restlessness and upper respiratory tract infection. Adverse events led to discontinuation in 6.7% of cariprazine-treated patients versus 4.8% of placebo treated patients.
“This sNDA filing provides an important step towards the availability of a potential treatment option for the approximately 5 million patients suffering with bipolar I depression. These positive pivotal studies, demonstrated the efficacy and safety of VRAYLAR for the treatment of bipolar depression,” said David Nicholson, Chief Research & Development Officer at Allergan. ” “VRAYLAR is the flagship product of our Psychiatry portfolio and demonstrates Allergan’s commitment to the mental health community.”
Cariprazine was approved by the FDA in September 2015 and is marketed as VRAYLAR® in the US for the treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
About Cariprazine Trials in Bipolar I Depression
The efficacy and safety of cariprazine in bipolar depression was evaluated in a total of four, 6- and 8-week randomized, placebo-controlled studies. One exploratory study phase 2 study RGH-MD-52 in bipolar I & II patients, and 3 pivotal studies (RGH-MD-56, 53 & 54) in bipolar I patients.
RGH MD 52 was a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comparing cariprazine to placebo in outpatients with a primary diagnosis of bipolar I or II disorder who were experiencing a major depressive episode. The study randomized 233 patients with bipolar I and bipolar II disorder to 1 of 3 dose groups for 8 weeks of double blind treatment: cariprazine 0.25 mg to 0.75 mg; cariprazine 1.5 mg to 3 mg; or placebo.
RGH-MD-56 was a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group clinical trial in adult patients with bipolar I depression. A total of 584 patients were randomized to evaluate the efficacy, safety, and tolerability of cariprazine 0.75 mg, 1.5 mg and 3 mg compared to placebo in the treatment of outpatients with bipolar I depression. Patients underwent a no-drug screening period of approximately 7-14 days, followed by 8 weeks of double-blind treatment (primary endpoint was 6-weeks) and a 1-week, no investigational product safety follow-up period.
RGH-MD-53 and RGH-MD-54 were identical Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, fixed-dose clinical trials in adult patients with bipolar I depression. Patients were randomized in both studies aiming to evaluate the efficacy, safety, and tolerability of cariprazine 1.5 mg and 3 mg compared to placebo in outpatients with bipolar I depression. Patients underwent a no-drug screening period of approximately 7-14 days, followed by 6 weeks of double-blind treatment and a 1-week, no investigational product safety follow-up period.
About VRAYLAR® (cariprazine)
VRAYLAR is an oral, once daily atypical antipsychotic approved for the treatment of schizophrenia in adults, with a recommended dose range of 1.5 to 6 mg/day and 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.
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-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. Pharmacodynamic studies with cariprazine have shown that it acts as a partial agonist with high binding affinity at dopamine D3, dopamine D2, and serotonin 5-HT1A receptors. 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-HT2B and 5-HT2A 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-HT2C and α1A– 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 by Allergan, in the U.S. and Canada. For more than a decade both companies have conducted over 20 clinical trials enrolling thousands of patients worldwide to evaluate the efficacy and safety of cariprazine for patients suffering from a broad range of mental health illnesses.
Visit www.vraylar.com for more information.
INDICATION AND USAGE
VRAYLAR (cariprazine) is indicated in adults for the treatment of schizophrenia and for the acute treatment of manic or mixed episodes of bipolar I disorder.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical leader. 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.
Allergan’s success is powered by our 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.
SOURCE: Allergan
Post Views: 143
