Phase III CREDENCE study shows reduction in CV and renal risks for type 2 diabetes patients

Janssen Pharmaceutical announced new results from the Phase III CREDENCE study, showing that Invokana (canagliflozin) demonstrated a 30 percent reduction in the risk of the primary composite endpoint, comprised 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.

The landmark study evaluated the efficacy and safety of Invokana versus placebo in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) when used in addition to standard of care. Study results also showed Invokana reduced the risk of the secondary CV endpoints, including the risk of CV death and hospitalization for heart failure by 31 percent, 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 percent. 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. Furthermore, Invokana showed a 20 percent reduction in the risk of the secondary endpoints of MACE, which is composed of nonfatal MI, nonfatal stroke, and CV death, a 31 percent reduction in the risk of the composite of CV death and hospitalization for heart failure, and a 39 percent reduction in the risk of hospitalization for heart failure alone. The incidence rates of adverse events and serious adverse events were numerically lower for patients treated with Invokana as compared to placebo.

The data were presented at 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.

See: "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy" Vlado Perkovic et al. NEJM April 14, 2019 DOI: 10.1056/NEJMoa1811744

Comment: In March 2019, 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.