- Johnson & Johnson on Sunday announced full results of a major Invokana renal outcomes trial that showed the drug reduced the risk of diabetics dying or having kidney-related complications by 30%.
- The 4,400-patient study was halted early because an independent review committee determined last year the results would be positive. As a result of the early stoppage, J&J has already asked the Food and Drug Administration to add the renal data to the Invokana label, which would give it a marketing edge over rival pills from AstraZeneca and Eli Lilly.
- Specialists view kidney and heart safety as essential for diabetes drugs because these complications are more likely to lead to hospitalization or death than blood sugar instability.
Diabetes is a metabolic disease with numerous complications. Even if they can control their blood sugar levels, diabetics are more likely to suffer cardiovascular and renal disease. So diabetes specialists and regulators want new drugs to not only be safe for the heart and kidneys, but also to be capable of preventing cardiovascular and renal complications.
Invokana (canagliflozin) is part of a relatively new class of diabetes drugs called SGLT-2 inhibitors, which help to control blood sugar by increasing glucose output in the urine — a profile that raises questions about whether they are safe for the kidneys. Other drugs in this class are Jardiance (empagliflozin) from Eli Lilly and Boehringer Ingelheim, and Farxiga (dapagliflozin) from AstraZeneca.
Jardiance was the first to show that SGLT-2 inhibitors could actually avert heart attacks, strokes and cardiovascular death when Lilly reported data from the EMPA-REG OUTCOMES trial, a claim that has since been matched by both Farxiga and Invokana.
Now Invokana is the first to show another benefit: reducing dialysis, kidney transplantations and renal death. Full data from the CREDENCE trial were released at the International Society of Nephrology World Congress in Australia and simultaneously published in the New England Journal of Medicine.
The trial's main outcome was a composite of end-stage renal disease, doubling of the serum creatinine level from baseline and sustained over 30 days, or death from renal or cardiovascular disease. CREDENCE found that patients taking Invokana were 30% less likely to have suffered any of those outcomes than patients taking placebo, with event rates of 43.2 per 1,000 patient-years for Invokana and 61.2 per 1,000 patient-years for placebo.
CREDENCE also confirmed earlier heart-related outcomes findings, showing reduced risk of composite measures of cardiovascular death, hospitalization for heart failure, stroke and myocardial infarction.
"Overall, the importance of CREDENCE, a well done and large clinical trial, cannot be overstated," wrote Julie Ingelfinger and Clifford Rosen, respectively of the Tufts University School of Medicine and the Maine Medical Center Research Institute, in an editorial in the New England Journal of Medicine. Both work for the Journal as editors.
If the FDA agrees to put kidney safety on the Invokana label, the drug would likely enjoy a marketing edge for some years to come. Lilly and Boehringer only initiated a kidney outcomes trial in January, with results expected in 2022, while AstraZeneca does not appear to have begun such a trial.
Invokana is the only SGLT-2 that carries a warning of lower-limb amputations, however, so having an additional marketing claim will be useful as the three drugs fight for market share.