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FDA approves canagliflozin to treat diabetic kidney disease, heart failure hospitalization
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The FDA approved a new indication for the SGLT2 inhibitor canagliflozin to reduce the risk for end-stage renal disease, worsening of kidney function, cardiovascular death and hospitalization for heart failure among adults with type 2 diabetes and diabetic kidney disease, according to a press release from Janssen.
The new approval is based on results from the phase 3 CREDENCE study, which evaluated the efficacy and safety of canagliflozin (Invokana) vs. placebo for adults with type 2 diabetes and CKD. As Endocrine Today previously reported, the steering committee behind the CREDENCE trial announced an early stop of the study in July 2018, based on the achievement of prespecified efficacy criteria.
"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," James List, MD, PhD, global therapeutic area head of cardiovascular and metabolism for Janssen Research and Development, said in the release. "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."
LaVarne A. Burton, president and CEO of the American Kidney Fund, said in a statement that the approval comes at a time of heightened focus on renal health.
"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,” Burton said in the release. “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 CREDENCE trial, originally estimated to be completed by 2020, was designed to assess whether canagliflozin had a renal and vascular protective effect in reducing the progression of renal impairment relative to placebo in participants with type 2 diabetes, stage 2 or 3 CKD and macroalbuminuria. The trial enrolled 4,401 patients with type 2 diabetes and an estimated glomerular filtration rate between 30 mL/min/1.73 m2 and 90 mL/min/1.73 m2, and albuminuria, defined as a urinary albumin to creatinine ratio between 300 mg/g and 5,000 mg/g.
Researchers found ESRD, doubling of serum creatine and renal or CV death occurred for 340 patients who took placebo and for 245 patients who took canagliflozin (HR= 0.70; 30% reduction with canagliflozin). Regarding renal-specific outcomes, a composite of ESRD, doubling of serum creatine or renal death occurred for 224 patients who took placebo and 153 patients who took canagliflozin (HR = 0.66; 34% reduction with canagliflozin).
In addition, researchers observed a 32% risk reduction of ESRD among patients who took canagliflozin (HR = 0.68), as well as a 28% risk reduction for starting dialysis, having a kidney transplant or experiencing renal death.
In subgroup analyses of CREDENCE presented at the American Diabetes Association Scientific Sessions in June, researchers reported that canagliflozin also reduced risk for a CV event or renal failure among adults with type 2 diabetes and CKD regardless of prior history of CVD, making CREDENCE the first study to show a CV benefit for any type 2 diabetes treatment in a primary prevention cohort.
"For nearly two decades, we've been searching for a treatment that can help us intervene earlier to slow kidney disease progression,” George Bakris, MD, professor of medicine and director of the Comprehensive Hypertension Center at the University of Chicago and a CREDENCE study investigator, said in the release. “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 type 2 diabetes and DKD." – by Regina Schaffer
Disclosures: Burton is president and CEO of the American Kidney Fund. List is global therapeutic area head of cardiovascular and metabolism for Janssen Research and Development.
Editor's Note: This article was updated on Oct. 1, 2019, to correctly identify LaVarne A. Burton. The Editors regret the error.
Perspective
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Jacob A. Udell, MD, MPH, FRCPC
This FDA approval is based on really solid clinical trial evidence from the CREDENCE study that comes after several other CV outcome trials in patients with diabetes with less pronounced kidney disease both by canagliflozin itself and other drugs in the class. All of them appear to have quite a remarkable benefit with regards to CV risk reduction. In CREDENCE, there was a real focus for the first time as a primary endpoint on kidney protection. It’s great for patients. The safety profile seemed to relieve a lot of the concerns that were earlier suggested by this specific drug or the class of medication with regards to particular side effects that are concerning to patients and clinicians like diabetic ketoacidosis and limb amputations. There wasn’t a significant increase in risk seen, so that’s really reassuring.
Having more choices amongst the class of therapies that now have strong evidence for heart and kidney protection can only benefit patients. It will be great for the field. It will hopefully drive cost down because there will be more options and more competition between the class of medication. It may spark more investment by the pharmaceutical companies and public agencies to research other potential types of patients that might benefit from this class of drugs. Soon, there will be more experience among clinicians using SGLT2 inhibitors in routine clinical practice so that if there are residual concerns about safety or particular patient populations that we have to be cautious about, we will learn more studying their use in the health system.
The other thing we need to keep on the horizon is that dapagliflozin (Farxiga, AstraZeneca), another drug in the class, is getting fast-track evaluation by the FDA based on their emerging evidence. One of the studies that really sparked that is DAPA-HF, where they are starting to study patients with heart disease but without diabetes, specifically in heart failure with reduced ejection fraction. That’s really going to further open up the field dramatically. Further provocative studies like that are hopefully on the horizon.
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