The Janssen Pharmaceutical Companies of Johnson & Johnson announced the U.S. Food and Drug Administration (FDA) approved a new indication for INVOKANA® (canagliflozin) to reduce the risk of end-stage kidney disease (ESKD), worsening of kidney function, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes and diabetic kidney disease (nephropathy) with a certain amount of protein in the urine. INVOKANA® is now the only type 2 diabetes medicine indicated to both treat diabetic kidney disease and reduce the risk of hospitalization for heart failure in patients with T2D and DKD.
T2D is the leading cause of kidney disease in the United States and the fifth fastest-growing cause of death around the world. 2
"With the approval of these new uses, INVOKANA® is now the only diabetes medicine indicated to help type 2 diabetes patients reduce the risks associated with diabetic kidney disease, including hospitalization for heart failure," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. "This significant advancement addresses serious unmet needs and could change the trajectory of care for the many millions of patients living with type 2 diabetes and diabetic kidney disease."
In the United States, one in three people with T2D has DKD,1 which multiplies the risk of cardiovascular complications including heart failure and CV death, and puts patients on a trajectory to dialysis and kidney transplant. Additionally, heart failure is one of the leading causes of hospitalization,3 with a high unmet need for effective treatment options. With this approval, INVOKANA® is the only type 2 diabetes medicine indicated to reduce the risk of hospitalization for heart failure in patients with T2D and DKD, and is the first new treatment option in nearly 20 years indicated to slow the progression of DKD in these patients.
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"Given the nation's heightened focus on kidney health at the highest levels of government, this approval couldn't have come at a better time and offers real hope for patients with type 2 diabetes and diabetic kidney disease," said LaVarne A. Burton, President and Chief Executive Officer, American Kidney Fund. "We know that the real battle to turn the tide on kidney disease is in early detection and slowing its progression so that patients stay healthier and fewer patients reach kidney failure. We are so grateful that advances in kidney disease research are producing treatment options that help to slow the progression of diabetic kidney disease and reduce the risk of hospitalization for heart failure."
The new indication is based on results from the landmark Phase 3 CREDENCE study in patients with T2D and DKD, which was stopped early because it met the prespecified criteria for efficacy. In CREDENCE, INVOKANA® 100 mg demonstrated a 30 percent reduction in the risk of the primary composite endpoint, comprising end-stage kidney disease (ESKD), doubling of serum creatinine and renal or CV death.† Results also showed INVOKANA® reduced the risk of secondary CV endpoints, including a 39 percent reduction in the risk of hospitalization for heart failure. Overall, adverse events and serious adverse events were similar but numerically lower in the INVOKANA® group compared to placebo. The rates of diabetic ketoacidosis and genital mycotic infections were numerically higher in the INVOKANA® group, as observed in other clinical trials. Additionally, there was no imbalance in lower limb amputation or bone fracture in this trial and no new safety signals were identified.
"Millions of T2D patients around the world have DKD and almost half of them aren't even aware of it. By the time they are referred to a nephrologist, it is often too late because their disease has progressed to the point where dialysis is inevitable," said CREDENCE study investigator George Bakris, M.D., Professor of Medicine and Director, Comprehensive Hypertension Center, University of Chicago.‡ "For nearly two decades, we've been searching for a treatment that can help us intervene earlier to slow kidney disease progression. With the approval for this new indication for INVOKANA®, physicians will not only be able to help reduce the risks associated with diabetic kidney disease, but also reduce the risk of hospitalization for heart failure in patients with T2D and DKD."
CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) is the first dedicated renal outcomes study of any sodium-glucose co-transporter 2 (SGLT2) inhibitor in patients with T2D and DKD in addition to standard of care. The study is a randomized, double-blind, event-driven, placebo-controlled, parallel-group, 2-arm, multicenter study, which evaluated 4,401 patients with T2D, Stage 2 or 3 DKD (defined as an estimated glomerular filtration rate [eGFR] of ≥30 to <90 mL/min/1.73 m2) and macroalbuminuria (defined as urinary albumin-to-creatinine ratio [ACR] >300 to ≤5,000 mg/g) who were receiving standard of care, including a maximum tolerated labeled daily dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB). The primary efficacy outcome for these analyses was the composite of end-stage kidney disease (dialysis, transplant, or eGFR <15), doubling of serum creatinine, and renal death or cardiovascular (CV) death. Specified secondary outcomes included a composite of heart attack, stroke, or CV death and a composite of CV death or hospitalization for heart failure.