Study results published in the New England Journal of Medicine and featured in a special symposium at the American Diabetes Association 77th Scientific Sessions
RARITAN, NJ and SAN DIEGO, CA, USA I June 12, 2017 I Results from the landmark CANVAS Program showed INVOKANA® (canagliflozin) significantly reduced the combined risk of cardiovascular (CV) death, myocardial infarction (MI), and nonfatal stroke, versus placebo in patients with type 2 diabetes mellitus (T2DM) at risk for or with a history of CV disease. The results also showed canagliflozin treatment was associated with a reduced risk for hospitalization for heart failure (HHF) and demonstrated potential renal protective effects. These data from the integrated analysis of the CANVAS and CANVAS-R trials were published in the New England Journal of Medicine, and presented in a special symposium at the American Diabetes Association 77th Scientific Sessions on Monday, June 12, in San Diego.
Canagliflozin was studied in the longest, largest and broadest completed CV outcomes program of any sodium glucose cotransporter-2 (SGLT2) inhibitor. The CANVAS Program is the first program to assess the efficacy, safety, and durability of canagliflozin in more than 10,000 patients with T2DM, who had either a prior history of CV disease, or at least two CV risk factors.
Canagliflozin achieved a 14% reduction in the risk of the composite primary endpoint of CV mortality, nonfatal MI or nonfatal stroke (HR: 0.86; 95% CI: 0.75 to 0.97), and demonstrated the CV safety of canagliflozin (p<0.0001 for non-inferiority) and superiority compared to placebo (p=0.0158). Each component evenly contributed to this risk reduction, including nonfatal MI by 15% (HR: 0.85; 95% CI: 0.69 to 1.05), CV death by 13% (HR: 0.87; 95% CI: 0.72 to 1.06), and nonfatal stroke by 10% (HR: 0.90; 95% CI: 0.71 to 1.15). These outcomes were broadly consistent across various patient subgroups and across the individual components of the primary endpoint.
Additional analysis further revealed canagliflozin lowered the risk of HHF by 33% (HR: 0.67; 95% CI: 0.52 to 0.87) and provided sustained positive effects on glycemic and blood pressure control, as well as weight reduction, demonstrating wide-ranging durability.
In addition, canagliflozin showed potential renal protective effects, delaying progression of albuminuria and reducing the risk of clinically important renal composite outcomes (such as renal death, renal replacement therapy, and 40% reduction of eGFR) by 40% (HR: 0.60; 95% CI: 0.47 to 0.77). The ongoing, fully enrolled CREDENCE study, the first dedicated SGLT2 inhibitor renal outcomes trial in patients with T2DM and kidney disease, is further evaluating the effects of canagliflozin on renal and CV outcomes.
“The CANVAS results are important because they show clear benefit of canagliflozin over current standard-of-care treatments,” said Bruce Neal, M.B., Ch.B., Ph.D., principal investigator of the CANVAS and CANVAS-R trials, Professor of Medicine, University of New South Wales Sydney, and Senior Director, The George Institute for Global Health. “Furthermore, the CANVAS Program showed consistent reductions across all components of the primary study outcome – CV death, MI and stroke – indicating efficacy of canagliflozin for all the main CV risks likely to affect patients with diabetes.”
“Patients with diabetes are two to four times more likely to suffer from associated comorbidities, such as heart failure and kidney disease, and the CANVAS results demonstrate the potential of canagliflozin in reducing the risk for such conditions in high-risk type 2 diabetes patients,” said David Matthews, CANVAS Steering Committee co-chair, and Professor of Diabetic Medicine and Honorary Consultant Physician, University of Oxford. “These data are promising as they suggest canagliflozin may offer potential benefits for patients with type 2 diabetes, who are also facing complications from, or are at risk for, hospitalization for heart failure or kidney disease.”
“With the CANVAS Program results, we are excited to show the positive benefit-risk profile for cardiovascular and renal endpoints,” said James F. List, M.D., Ph.D., Global Therapeutic Head, Cardiovascular & Metabolism, Janssen. “The success of this Program is especially encouraging for our ongoing and future studies exploring the potential of canagliflozin in additional patient populations.”
Overall adverse events seen in the CANVAS Program were consistent with previous findings. An increased risk of amputation with canagliflozin was seen in both the completed CANVAS and CANVAS-R studies. This is consistent with the observation made by the study’s Independent Data Monitoring Committee (IDMC) in 2016, and the data shared with Health Authorities and Health Care Professionals. There was an increased risk of amputation (6.3 vs. 3.4/1000 patient-years) corresponding to a hazard ratio (HR) of 1.97. The highest absolute risk of amputation occurred in patients with a prior history of amputation or peripheral vascular disease, but the relative risk for amputation with canagliflozin was comparable across these subgroups. These findings have been shared by the U.S. FDA and will be reflected in the U.S. Prescribing Information for canagliflozin. The risk has been included in the canagliflozin European Union Summary of Product Characteristics (SmPC).
Separately, while an increased risk of adjudicated low trauma fracture was identified in the CANVAS study, no increase was observed in the CANVAS-R study. A full assessment is ongoing to provide a complete safety review of these results.
About the CANVAS Program
The CANVAS Program is composed of two, nearly-identical large outcomes studies CANVAS (CANagliflozin CardioVascular Assessment Study (NCT01032629) and CANVAS-R (Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects with T2DM (NCT01989754).
The CANVAS Program is the largest completed CV outcomes program of any SGLT2 inhibitor to date, with a total of 10,142 patients – 4,330 patients in CANVAS and 5,812 patients in CANVAS-R. In the randomized, placebo-controlled Phase 3/4 studies, a vast majority of patients were obese, with a history of hypertension, and 66% of patients had a history of CV disease (14% had a history of heart failure) and 34% of patients had at least two CV risk factors. The study assessed the safety of canagliflozin relative to placebo in patients receiving specific commonly-used diabetes agents. The primary endpoint was defined as major adverse CV events (MACE), composed of nonfatal MI, nonfatal stroke and CV death, and the secondary endpoint was defined as progression of albuminuria, beta-cell function, eGFR changes and UACR.
In the CANVAS study, patients were randomly assigned in a 1:1:1 ratio to placebo, canagliflozin 100mg and canagliflozin 300mg. The mean and median exposure to investigational product was approximately 4.3 and 5.8 years, respectively. The mean and median follow-up time was 5.7 and 6.1 years, respectively.
In the CANVAS-R study, patients were randomly assigned in a 1:1 ratio to placebo or canagliflozin 100mg (with an investigator option to up-titrate to 300mg if the patient required additional glycemic control, provided the 100mg dosage was well tolerated). The mean and median exposure to investigational product was approximately 1.8 and 1.9 years, respectively. The mean and median follow-up time was 2.1 years.
These CANVAS and CANVAS-R studies were designed to be highly similar in patient population, procedures and assessments, evaluating the effects of canagliflozin on CV events. This approach is demonstrated in three published studies: “Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)—A randomized placebo-controlled trial,” published online by American Heart Journal; “Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study–Renal (CANVAS-R): A randomized, placebo-controlled trial,” published online by Diabetes, Obesity and Metabolism; and “Optimizing the analysis strategy for the CANVAS Program – a pre-specified plan for the integrated analyses of the CANVAS and CANVAS-R trials,” published online by Diabetes, Obesity and Metabolism.
About INVOKANA®
In March 2013, the U.S. FDA approved canagliflozin – INVOKANA® – as a single agent. In two studies comparing INVOKANA® plus metformin to current standard treatments plus metformin – one studying sitagliptin[i] and the other studying glimepiride[ii] – INVOKANA® dosed at 300 mg provided greater reductions in A1C levels and body weight than either comparator. In the two studies, the overall incidence of adverse events was similar with INVOKANA® and the comparators. INVOKANA® continues to be the number-one prescribed SGLT2 inhibitor leading with more prescriptions than all other SGLT2 inhibitors combined in U.S. in 2017*. Since its launch, more than 14 million prescriptions have been written for INVOKANA® in the U.S.
Janssen Pharmaceuticals, Inc. and its affiliates have rights to canagliflozin through a license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen Pharmaceuticals, Inc. and its affiliates have marketing rights in Africa, parts of Asia, Australia, Europe, the Middle East, New Zealand, North America and South America.
INVOKANA® is approved as a single agent in Argentina, Aruba, Australia, Azerbaijan, Bahrain, Bolivia, Brazil, Brunei, Canada, Chile, Colombia, Costa Rica, Curacao, Dominican Republic, Egypt, El Salvador, the European Union (28 countries), Ghana, Guatemala, Honduras, Hong Kong, Iceland, India, Israel, Jamaica, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Morocco, New Zealand, Nicaragua, Norway, Oman, Panama, Paraguay, Peru, Philippines, Qatar, Russia, Saudi Arabia, Serbia, Singapore, South Korea, Switzerland, Taiwan, Thailand, Ukraine, United Arab Emirates and the United States.
WHAT IS INVOKANA®?
INVOKANA® is a prescription medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. INVOKANA® is not for people with type 1 diabetes or with diabetic ketoacidosis (increased ketones in blood or urine). It is not known if INVOKANA® is safe and effective in children under 18 years of age.
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal.
SOURCE: Janssen
Post Views: 198
Study results published in the New England Journal of Medicine and featured in a special symposium at the American Diabetes Association 77th Scientific Sessions
RARITAN, NJ and SAN DIEGO, CA, USA I June 12, 2017 I Results from the landmark CANVAS Program showed INVOKANA® (canagliflozin) significantly reduced the combined risk of cardiovascular (CV) death, myocardial infarction (MI), and nonfatal stroke, versus placebo in patients with type 2 diabetes mellitus (T2DM) at risk for or with a history of CV disease. The results also showed canagliflozin treatment was associated with a reduced risk for hospitalization for heart failure (HHF) and demonstrated potential renal protective effects. These data from the integrated analysis of the CANVAS and CANVAS-R trials were published in the New England Journal of Medicine, and presented in a special symposium at the American Diabetes Association 77th Scientific Sessions on Monday, June 12, in San Diego.
Canagliflozin was studied in the longest, largest and broadest completed CV outcomes program of any sodium glucose cotransporter-2 (SGLT2) inhibitor. The CANVAS Program is the first program to assess the efficacy, safety, and durability of canagliflozin in more than 10,000 patients with T2DM, who had either a prior history of CV disease, or at least two CV risk factors.
Canagliflozin achieved a 14% reduction in the risk of the composite primary endpoint of CV mortality, nonfatal MI or nonfatal stroke (HR: 0.86; 95% CI: 0.75 to 0.97), and demonstrated the CV safety of canagliflozin (p<0.0001 for non-inferiority) and superiority compared to placebo (p=0.0158). Each component evenly contributed to this risk reduction, including nonfatal MI by 15% (HR: 0.85; 95% CI: 0.69 to 1.05), CV death by 13% (HR: 0.87; 95% CI: 0.72 to 1.06), and nonfatal stroke by 10% (HR: 0.90; 95% CI: 0.71 to 1.15). These outcomes were broadly consistent across various patient subgroups and across the individual components of the primary endpoint.
Additional analysis further revealed canagliflozin lowered the risk of HHF by 33% (HR: 0.67; 95% CI: 0.52 to 0.87) and provided sustained positive effects on glycemic and blood pressure control, as well as weight reduction, demonstrating wide-ranging durability.
In addition, canagliflozin showed potential renal protective effects, delaying progression of albuminuria and reducing the risk of clinically important renal composite outcomes (such as renal death, renal replacement therapy, and 40% reduction of eGFR) by 40% (HR: 0.60; 95% CI: 0.47 to 0.77). The ongoing, fully enrolled CREDENCE study, the first dedicated SGLT2 inhibitor renal outcomes trial in patients with T2DM and kidney disease, is further evaluating the effects of canagliflozin on renal and CV outcomes.
“The CANVAS results are important because they show clear benefit of canagliflozin over current standard-of-care treatments,” said Bruce Neal, M.B., Ch.B., Ph.D., principal investigator of the CANVAS and CANVAS-R trials, Professor of Medicine, University of New South Wales Sydney, and Senior Director, The George Institute for Global Health. “Furthermore, the CANVAS Program showed consistent reductions across all components of the primary study outcome – CV death, MI and stroke – indicating efficacy of canagliflozin for all the main CV risks likely to affect patients with diabetes.”
“Patients with diabetes are two to four times more likely to suffer from associated comorbidities, such as heart failure and kidney disease, and the CANVAS results demonstrate the potential of canagliflozin in reducing the risk for such conditions in high-risk type 2 diabetes patients,” said David Matthews, CANVAS Steering Committee co-chair, and Professor of Diabetic Medicine and Honorary Consultant Physician, University of Oxford. “These data are promising as they suggest canagliflozin may offer potential benefits for patients with type 2 diabetes, who are also facing complications from, or are at risk for, hospitalization for heart failure or kidney disease.”
“With the CANVAS Program results, we are excited to show the positive benefit-risk profile for cardiovascular and renal endpoints,” said James F. List, M.D., Ph.D., Global Therapeutic Head, Cardiovascular & Metabolism, Janssen. “The success of this Program is especially encouraging for our ongoing and future studies exploring the potential of canagliflozin in additional patient populations.”
Overall adverse events seen in the CANVAS Program were consistent with previous findings. An increased risk of amputation with canagliflozin was seen in both the completed CANVAS and CANVAS-R studies. This is consistent with the observation made by the study’s Independent Data Monitoring Committee (IDMC) in 2016, and the data shared with Health Authorities and Health Care Professionals. There was an increased risk of amputation (6.3 vs. 3.4/1000 patient-years) corresponding to a hazard ratio (HR) of 1.97. The highest absolute risk of amputation occurred in patients with a prior history of amputation or peripheral vascular disease, but the relative risk for amputation with canagliflozin was comparable across these subgroups. These findings have been shared by the U.S. FDA and will be reflected in the U.S. Prescribing Information for canagliflozin. The risk has been included in the canagliflozin European Union Summary of Product Characteristics (SmPC).
Separately, while an increased risk of adjudicated low trauma fracture was identified in the CANVAS study, no increase was observed in the CANVAS-R study. A full assessment is ongoing to provide a complete safety review of these results.
About the CANVAS Program
The CANVAS Program is composed of two, nearly-identical large outcomes studies CANVAS (CANagliflozin CardioVascular Assessment Study (NCT01032629) and CANVAS-R (Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects with T2DM (NCT01989754).
The CANVAS Program is the largest completed CV outcomes program of any SGLT2 inhibitor to date, with a total of 10,142 patients – 4,330 patients in CANVAS and 5,812 patients in CANVAS-R. In the randomized, placebo-controlled Phase 3/4 studies, a vast majority of patients were obese, with a history of hypertension, and 66% of patients had a history of CV disease (14% had a history of heart failure) and 34% of patients had at least two CV risk factors. The study assessed the safety of canagliflozin relative to placebo in patients receiving specific commonly-used diabetes agents. The primary endpoint was defined as major adverse CV events (MACE), composed of nonfatal MI, nonfatal stroke and CV death, and the secondary endpoint was defined as progression of albuminuria, beta-cell function, eGFR changes and UACR.
In the CANVAS study, patients were randomly assigned in a 1:1:1 ratio to placebo, canagliflozin 100mg and canagliflozin 300mg. The mean and median exposure to investigational product was approximately 4.3 and 5.8 years, respectively. The mean and median follow-up time was 5.7 and 6.1 years, respectively.
In the CANVAS-R study, patients were randomly assigned in a 1:1 ratio to placebo or canagliflozin 100mg (with an investigator option to up-titrate to 300mg if the patient required additional glycemic control, provided the 100mg dosage was well tolerated). The mean and median exposure to investigational product was approximately 1.8 and 1.9 years, respectively. The mean and median follow-up time was 2.1 years.
These CANVAS and CANVAS-R studies were designed to be highly similar in patient population, procedures and assessments, evaluating the effects of canagliflozin on CV events. This approach is demonstrated in three published studies: “Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)—A randomized placebo-controlled trial,” published online by American Heart Journal; “Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study–Renal (CANVAS-R): A randomized, placebo-controlled trial,” published online by Diabetes, Obesity and Metabolism; and “Optimizing the analysis strategy for the CANVAS Program – a pre-specified plan for the integrated analyses of the CANVAS and CANVAS-R trials,” published online by Diabetes, Obesity and Metabolism.
About INVOKANA®
In March 2013, the U.S. FDA approved canagliflozin – INVOKANA® – as a single agent. In two studies comparing INVOKANA® plus metformin to current standard treatments plus metformin – one studying sitagliptin[i] and the other studying glimepiride[ii] – INVOKANA® dosed at 300 mg provided greater reductions in A1C levels and body weight than either comparator. In the two studies, the overall incidence of adverse events was similar with INVOKANA® and the comparators. INVOKANA® continues to be the number-one prescribed SGLT2 inhibitor leading with more prescriptions than all other SGLT2 inhibitors combined in U.S. in 2017*. Since its launch, more than 14 million prescriptions have been written for INVOKANA® in the U.S.
Janssen Pharmaceuticals, Inc. and its affiliates have rights to canagliflozin through a license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen Pharmaceuticals, Inc. and its affiliates have marketing rights in Africa, parts of Asia, Australia, Europe, the Middle East, New Zealand, North America and South America.
INVOKANA® is approved as a single agent in Argentina, Aruba, Australia, Azerbaijan, Bahrain, Bolivia, Brazil, Brunei, Canada, Chile, Colombia, Costa Rica, Curacao, Dominican Republic, Egypt, El Salvador, the European Union (28 countries), Ghana, Guatemala, Honduras, Hong Kong, Iceland, India, Israel, Jamaica, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Morocco, New Zealand, Nicaragua, Norway, Oman, Panama, Paraguay, Peru, Philippines, Qatar, Russia, Saudi Arabia, Serbia, Singapore, South Korea, Switzerland, Taiwan, Thailand, Ukraine, United Arab Emirates and the United States.
WHAT IS INVOKANA®?
INVOKANA® is a prescription medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. INVOKANA® is not for people with type 1 diabetes or with diabetic ketoacidosis (increased ketones in blood or urine). It is not known if INVOKANA® is safe and effective in children under 18 years of age.
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal.
SOURCE: Janssen
Post Views: 198
