If this new indication is approved, Invokana® would be the first diabetes medication to treat both T2D and CKD.
Canagliflozin (Invokana, Janssen Pharmaceutical Companies of Johnson and Johnson) demonstrated a 30% reduction in the risk of progression to end-stage kidney disease (ESKD), defined as the need for renal replacement therapy (RRT) such as chronic dialysis or renal transplant; doubling of serum creatinine, a key predictor of ESKD; and renal or cardiovascular (CV) death, according to study results being at the the International Society of Nephrology (ISN) 2019 World Congress of Nephrology (WCN) in Melbourne, Australia, and simultaneously published in The New England Journal of Medicine.
Results from the phase 3 CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) also showed Invokana® reduced the risk of the secondary CV endpoints, including the risk of CV death and hospitalization for heart failure by 31%, major adverse CV events (MACE; composite of nonfatal myocardial infarction [MI], nonfatal stroke and CV death) by 20 percent, and the risk of hospitalization for heart failure alone by 39%. Importantly, the study showed no imbalance in amputation or bone fracture. Additionally, no new safety concerns were identified in this study of high-risk patients.
The clinical trial was a randomized, double-blind, event-driven, placebo-controlled, parallel-group, 2-arm, multicenter study that included 4,401 patients with type 2 diabetes, stage 2 or 3 CKD (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 angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
The incidence rates of adverse events and serious adverse events were numerically lower for patients treated with the study drug compared with placebo. There were no observed differences in the incidence of amputations (HR: 1.11; 95% CI: 0.79 to 1.56) or adjudicated fractures (HR: 0.98; 95% CI: 0.70 to 1.37), which could assauge concerns that were first raised in the CANVAS trial. The researchers noted the differences in the incidence of amputations could have been due to different study populations in the 2 trials.
Last month, officials with Janssen included the CREDENCE data in the submission of a supplemental New Drug Application to the FDA for Invokana® to reduce the risk of ESKD, the doubling of serum creatinine, and renal or CV death for adults with CKD and T2D. This followed an Independent Data Monitoring Committee meeting in July 2018, where the committee recommended that the CREDENCE trial stop early because it met the prespecified criteria for efficacy. If this new indication is approved, Invokana® would be the first diabetes medication to treat both T2D and CKD.