Johnson & Johnson (JNJ) ‘s Janssen Pharmaceuticals has announced that Health Canada has approved a new indication for the glucose-lowering drug Invokana (canagliflozin): Complementary drugs for standard care therapies for adult patients with type 2 diabetes (T2D) and diabetic nephropathy (DN; Also called diabetic kidney disease, DKD) with proteinuria(>33.9mg/mmol), reducing end-stage renal disease (ESKD), doubling serum creatinine, and cardiovascular (CV) risk . This approval makes Invokana the only diabetes drug approved in Canada for this group of patients.
In the United States, the FDA approved Invokana in September 2019: for adults with T2D and DKD and a certain amount of protein in the urine, reducing the risk of ESKD, worsening renal function, CV death, and hospitalization for heart failure. With this approval, Invokana is the first type 2 diabetes drug to reduce the risk of hospitalization for heart failure in patients with both T2D and DKD, and the first new drug to delay the progression of DKD in these patients in nearly 20 years.
Type 2 diabetes is the leading cause of kidney disease and the fifth fastest growing cause of death worldwide. In Canada, one in every two T2D patients shows signs of kidney damage in their lifetime. DKD is progressive and can lead to dialysis and kidney transplantation if left untreated. In addition, patients with DKD are at high risk for heart disease and stroke.
This approval is based on data from CREDENCE, a milestone Phase III clinical study that evaluates Invokana’s renal prognosis, the only completed renal prognosis study in diabetes medicine. In July 2018, JNJ made a decision to terminate the CREDENCE study prematurely, based on the recommendations of the Independent Data Monitoring Committee (IDMC) due to the particularly significant efficacy. CREDENCE is the first well-designed kidney prognosis study in T2D patients with DKD treated with standard care background therapies, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blocker (ARBS).
“The approval of the new Invokana indication is a significant step forward, given the increased prevalence of diabetic nephropathy in patients with type 2 diabetes,” said Adeera Levin, lead national researcher at CREDENCE and Canadian University of British Columbia professor of medicine. Doctors can now offer patients a treatment plan that reduces cardiovascular and kidney risks associated with diabetic nephropathy. ”
Invokana is a new hypoglycemic agent of the SGLT2 inhibitor class. SGLT2 is a transporter involved in glucose reabsorption in the proximal tubules of the kidney. Invokana mainly reduces the reabsorption of glucose by the kidney and increases the excretion of glucose in the urine by inhibiting SGLT2 expressed in the kidney, thereby reducing the blood glucose level, and the effect of reducing blood glucose is not dependent on β cell function and insulin resistance. Compared with non-diabetics, the kidneys of people with type 2 diabetes are able to reabsorb large amounts of glucose into the bloodstream, which may push blood sugar levels higher. In addition to a clear hypoglycemic effect, Invokana can also provide additional benefits such as weight loss, delayed proteinuria progression, and decreased blood pressure.
At present, Invokana’s indications are: (1) combining diet control and exercise to reduce blood sugar levels in adults with type 2 diabetes; (2) used in adults with type 2 diabetes with cardiovascular disease to reduce the risk of major adverse cardiovascular events , such as heart attack, stroke and death; (3) for adult patients with type 2 diabetes and diabetic nephropathy with proteinuria, reduced the risk of end-stage renal disease (ESKD), worsening renal function, cardiovascular death, and hospitalization for heart failure. Not suitable for patients with type 1 diabetes or patients with diabetic ketoacidosis. The safety and effectiveness of the drug in children under 18 are currently unknown.
References:
- New Analysis from Landmark CREDENCE Study Shows the Efficacy and Safety Profiles of INVOKANA® (canagliflozin) are Consistent Across Various Levels of Kidney Function