Invokana Phase III Topline Data Show Significant Delay in Diabetic Kidney Disease Progression in Type 2 Diabetes Patients

On April 14, 2019, Janssen announced the latest Phase III clinical data for Invokana in the treatment of patients with type 2 diabetes and chronic kidney disease. Compared with the control group, Invokana significantly slowed the progression of kidney disease and reduced the risk of cardiovascular events (HR: 0.70; 95% CI: 0.59 to 0.82; p<0.0001). The release of these robust Phase III clinical data is expected to reverse the negative growth trend in Invokana’s sales.

Invokana (canagliflozin) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor approved by the FDA on March 29, 2013. In conjunction with diet and exercise, it is indicated to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Invokana lowers blood glucose levels by inhibiting SGLT2 expressed in the kidneys, thereby reducing renal glucose reabsorption and increasing urinary glucose excretion.

On April 14, 2019, Janssen Pharmaceuticals announced the latest Phase III CREDENCE clinical data on renal outcomes for Invokana. In patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), treatment with Invokana reduced the risk of the primary composite endpoint by 30% compared with the control group, thereby slowing the progression of renal and cardiovascular diseases.

CREDENCE was a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical study that enrolled 4,401 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) to evaluate the efficacy and safety of Invokana (100 mg) versus placebo in preventing adverse clinical renal and cardiovascular outcomes (Figure 1).

Figure 1. Design and Progress of the CREDENCE Trial

Baseline characteristics of patients in the Invokana group (n=2,202) and the placebo group (n=2,199) enrolled in the CREDENCE trial included the prevalence of hypertension, heart failure, and cardiovascular disease; duration of diabetes; glycated hemoglobin (HbA1c) levels; estimated glomerular filtration rate (eGFR); and urine albumin-to-creatinine ratio (UACR), among others (Figure 2).

Figure 2. Baseline Characteristics of Patients Enrolled in CREDENCE

CREDENCE clinical data demonstrated that, compared with placebo plus standard of care, Invokana plus standard of care reduced the primary composite endpoint by 30% (HR: 0.70; 95% CI: 0.59 to 0.82; p<0.0001), including progression to end-stage renal disease (eGFR decline, dialysis, or kidney transplantation, -32%; HR: 0.68; 95% CI: 0.54 to 0.86; p=0.0015), doubling of serum creatinine (-40%), and renal or cardiovascular death (-22%), significantly delaying the progression of kidney disease in patients with type 2 diabetes and chronic kidney disease (Figures 3/4).

Figure 3 Primary Composite Endpoint of the CREDENCE Trial

For secondary endpoints, compared with placebo, Invokana reduced the rate of cardiovascular death and heart failure-related hospitalizations by 31% (HR: 0.69; 95% CI: 0.57 to 0.83; p=0.0001) and the rate of serious adverse cardiovascular events (non-fatalMyocardial Infarction, nonfatal stroke and cardiovascular death (HR: 0.80; 95% CI: 0.67 to 0.95; p=0.0121), as well as a 39% reduction in heart failure–related hospitalization rate (HR: 0.61; 95% CI: 0.47 to 0.80; p=0.0003) (Figure 4).

Figure 4. Primary and Secondary Endpoints of the CREDENCE Trial

Compared with placebo, the Invokana group had lower rates of adverse events and serious adverse events, while safety data regarding amputation (HR: 1.11; 95% CI: 0.79 to 1.56) or fracture (HR: 0.98; 95% CI: 0.70 to 1.37) were largely consistent between the two groups (Figure 5).

Figure 5. Safety Data from the CREDENCE Trial

Invokana is the first therapy for type 2 diabetes (T2D) in nearly 20 years that can slow the progression of kidney disease. Clinical data from the CREDENCE trial demonstrate that Invokana can prevent patients from progressing to kidney failure and improve the quality of life for patients with chronic kidney disease (CKD) and T2D.

References:

1.INVOKANA® (canagliflozin) Significantly Reduces the Risk of Renal Failure in Patients with Type 2 Diabetes and Chronic Kidney Disease in the Landmark Phase 3 CREDENCE Study；

2.Invokana win in kidney patients could help J&J right the SGLT2 ship