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 - BioSpace

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  • INVOKANA® is the only medicine in nearly 20 years and the first diabetes medicine to demonstrate significant reduction in risk of renal failure, dialysis or kidney transplantation, and renal or cardiovascular death in this high-risk patient population
  • In the study, INVOKANA® significantly reduced the combined risk of cardiovascular death, myocardial infarction, and stroke, and demonstrated no imbalance in amputation or bone fracture
  • The CREDENCE study was halted early for positive efficacy findings and served as the basis for Janssen's March 2019 filing of a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA) for INVOKANA®

MELBOURNE, Australia, April 14, 2019 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson[1] announced today new results from the Phase 3 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.

The data were presented today during a late-breaking clinical trials session 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[2].

"Canagliflozin is the first medical breakthrough in nearly twenty years proven to slow the progression of chronic kidney disease in patients with diabetes at high risk of developing kidney failure," said Vlado Perkovici, M.B.B.S, Ph.D., F.A.S.N., F.R.A.C.P., CREDENCE Steering Committee co-chair, Executive Director, The George Institute for Global Health, Australia and Professor of Medicine, UNSW Sydney. "These impressive results from the CREDENCE study have significant clinical implications for preventing kidney failure and improving health for millions of people living with chronic kidney disease and type 2 diabetes."

"Diabetes is the leading cause of kidney failure for millions of people worldwide, and this clear need for a new treatment option was the motivation for initiating the CREDENCE study. Today, we are pleased to share study results that potentially could establish INVOKANA® as the only medicine to safely reduce the risk of renal failure in this high-risk patient population when added to current standard of care," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. "We are working closely with the U.S. FDA and health authorities worldwide to bring this important medicine to those living with these life-threatening conditions."

The Phase 3 CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation, NCT02065791[3]) clinical trial was a randomized, double-blind, event-driven, placebo-controlled, parallel-group, 2-arm, multicenter study. It evaluated 4,401 patients with T2D, 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).

"At Janssen, we tackle some of the world's most challenging and burdensome diseases, both by exploring the ability of our established medicines to meet unmet patient needs and by leveraging the cutting edge of science to develop entirely new medicines," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. "The CREDENCE clinical trial results demonstrate our commitment to helping patients, and bring us one step closer to treating the comorbidities associated with type 2 diabetes and meeting the unmet needs of the millions of people living with chronic kidney disease."

In March 2019[4], Janssen included the CREDENCE data in the submission of a supplemental New Drug Application to the U.S. 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[5], 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, and could be an important new treatment option for the millions of patients around the world who live with these illnesses.

Study Results
In the CREDENCE study, INVOKANA® showed a 30 percent reduction in the risk of the primary composite endpoint – comprised of progression to doubling of serum creatinine, ESKD, and renal or CV death (HR: 0.70; 95% CI: 0.59 to 0.82; p<0.0001). These findings were consistent across the individual components of the primary composite endpoint, as well as across all 15 prespecified subgroups tested. INVOKANA® reduced the risk of end-stage kidney disease by 32 percent (HR: 0.68; 95% CI: 0.54 to 0.86; p=0.0015).

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 (HR: 0.80; 95% CI: 0.67 to 0.95; p=0.0121), a 31 percent reduction in the risk of the composite of CV death and hospitalization for heart failure (HR: 0.69; 95% CI: 0.57 to 0.83; p=0.0001), and a 39 percent reduction in the risk of hospitalization for heart failure alone (HR: 0.61; 95% CI: 0.47 to 0.80; p=0.0003).

The incidence rates of adverse events and serious adverse events were numerically lower for patients treated with INVOKANA® as compared to 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).

At this time, INVOKANA®, which is currently indicated for the treatment of glycemia in patients with T2D and the reduction in MACE in patients with T2D and established CV disease, is contraindicated for patients with severe renal impairment (eGFR <30 mL/min/1.73 m2), ESKD, or patients on dialysis. In addition, INVOKANA® is not recommended when eGFR is persistently less than 45 mL/min/1.73 m2. Please see the Important Safety Information below and the full Prescribing Information[6] for additional details.

WHAT IS INVOKANA®?

INVOKANA® is a prescription medicine used:

  • along with diet and exercise to lower blood sugar (glucose) in adults with type 2 diabetes
  • to reduce the risk of major cardiovascular events such as heart attack, stroke, or death in adults with type 2 diabetes who have known cardiovascular disease. INVOKANA® is not for people with type 1 diabetes or with diabetic ketoacidosis (increased ketones in blood or urine). It is not known if INVOKANA® is safe and effective in children under 18 years of age.

IMPORTANT SAFETY INFORMATION

INVOKANA® can cause important side effects, including:

  • Amputations. INVOKANA® may increase your risk of lower-limb amputations.Amputations mainly involve removal of the toe or part of the foot; however, amputations involving the leg, below and above the knee, have also occurred. Some people had more than one amputation, some on both sides of the body. You may be at a higher risk of lower-limb amputation if you: have a history of amputation, have heart disease or are at risk for heart disease, have had blocked or narrowed blood vessels (usually in leg), have damage to the nerves (neuropathy) in the leg, or have had diabetic foot ulcers or sores. Call your doctor right away if you have new pain or tenderness, any sores, ulcers, or infections in your leg or foot. Your doctor may decide to stop your INVOKANA® for a while if you have any of these signs or symptoms. Talk to your doctor about proper foot care
  • Dehydration. INVOKANA® can cause some people to become dehydrated (the loss of too much body water), which may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You may be at higher risk of dehydration if you have low blood pressure, take medicines to lower your blood pressure (including diuretics [water pills]), are on a low sodium (salt) diet, have kidney problems, or are 65 years of age or older
  • Vaginal yeast infection. Women who take INVOKANA® may get vaginal yeast infections. Symptoms include: vaginal odor, white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese), or vaginal itching
  • Yeast infection of the penis (balanitis or balanoposthitis). Men who take INVOKANA® may get a yeast infection of the skin around the penis. Symptoms include: redness, itching, or swelling of the penis; rash of the penis; foul-smelling discharge from the penis; or pain in the skin around penis

Talk to your doctor about what to do if you get symptoms of a yeast infection of the vagina or penis.

Do not take INVOKANA® if you:

  • are allergic to canagliflozin or any of the ingredients in INVOKANA®.

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