The sNDA is seeking an indication for the reduction of major adverse events, including cardiovascular death, myocardial infarction, and stroke.
Janssen has submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for a new indication for canagliflozin (Invokana), an SGLT2 inhibitor, specifically for the reduction of the risk of major adverse cardiovascular events in adults with type 2 diabetes (T2D).
The list of major adverse events that have a reduced risk with the treatment includes cardiovascular death, myocardial infarction, and stroke. The new indication would apply to both Invokamet and Invokamet XR, 2 of the fixed-dose combination varieties of the drug.
Canagliflozin was approved by the FDA in March 2013 as a supplement to diet and exercise to improve glycemic control in adult patients with T2D.
"People with type 2 diabetes have a substantially increased risk of developing cardiovascular disease, and it's encouraging that we now have data to show INVOKANA may help address this challenge," James F List (pictured), MD, PhD, the global therapeutic area head of the cardiovascular & metabolism division at Janssen, said in a statement. "INVOKANA has shown a clear benefit in reducing cardiovascular risk in adults with type 2 diabetes and we look forward to working with FDA as it reviews our filing."
The application comes based on the data from the CANVAS program, which aimed to assess the safety and efficacy of canagliflozin in comparison with placebo in adults with T2D that were either at-risk for cardiovascular disease or with established cardiovascular disease.
CANVAS was composed of CANVAS and CANVAS-R and evaluated more than 10000 patients for 296 weeks (CANVAS) and 108 weeks (CANVAS-R). The CANVAS study also sought to investigate whether or possible heart failure related benefits demonstrated by similar drugs could be replicated. According to Robert Mentz, MD, an assistant professor of medicine at Duke University Medical School, the SGLT2 inhibitor could help prevent heart failure hospitalization in T2D patients.
Although SGLT2 inhibitors have been found to benefit T2D patients in cardiovascular risk, there have been concerns. In August 2017, the FDA reaffirmed warnings for canagliflozin related to amputations, which have been reported at a higher rate with SGLT2 inhibitors.
“At Janssen, patient safety is our highest priority. We continuously evaluate the safety and effectiveness of canagliflozin through ongoing clinical trials and post-marketing analyses to ensure prescribing information reflects the latest data,” Janssen told MD Magazine in a statement at the time. “Based on findings from the CANVAS Program, we worked with the U.S. FDA to update the product labels for canagliflozin to include the risk of lower-limb amputation—primarily of the toe or part of the foot—which was communicated previously to healthcare professionals by Janssen and by the FDA.”