FDA clears cardiovascular claim for J&J’s Invokana

Johnson & Johnson finally has some good news to report for its diabetes blockbuster Invokana, after the FDA approved a new cardiovascular outcome claim on its label.

The US regulator has approved SGLT2 inhibitor Invokana (canagliflozin)  to reduce the risk of major adverse cardiovascular events – including heart attack, stroke or death due to a cardiovascular cause – in adults with type 2 diabetes and established cardiovascular disease.

J&J says Invokana is the only oral diabetes treatment to reduce the risk of these cardiovascular events and is hoping that the new indication will help reverse a steep slide in sales of the drug in recent months.

The approval is based on the results of the CANVAS trial, which is ironically also the source of Invokana’s recent sales fall, shrinking by almost a quarter to $653 million in the first nine months of the year.

CANVAS showed that Invokana reduced the combined risk of heart attack, stroke and cardiovascular death by 14% compared to placebo overall, with an 18% advantage over control in patients with established cardiovascular disease. The problem was that the trial also showed that Invokana almost doubled the risk of lower limb amputations, and that was added to the product’s label as a ‘black box’ warning.

Cue a decline in market share against rival SGLT2 inhibitors from Boehringer Ingelheim/Eli Lilly and AstraZeneca, which have been growing at the expense of Invokana, particularly in prescriptions for new patients. The companies have worked hard to show with clinical data that the amputation risk is not a class effect.

Jennifer Taubert, chairman of pharmaceuticals at J&J, said at a conference last month that Invokana “really has been hampered by the warning in the label, and we’re still working closely with the agency and generating data, and a lot of real world evidence, to make sure that we understand and appropriately characterise any level of risk there.”

In June, the company reported real-world data at the American Diabetes Association (ADA) meeting from more than 140,000 patients treated with the product, saying it observed no elevated risk of below-knee lower extremity (BKLE) amputations.

J&J is also hoping for a boost later this year from its CREDENCE renal outcome study in patients with diabetic nephropathy, which was halted earlier this year on the recommendation of its data monitoring committee after hitting the mark on pre-specified efficacy endpoints.

The company said in July it would present the data at a medical conference before the end of the year, and would also be discussing the results with regulatory authorities.

In the meantime, J&J’s woes helped sales of Boehringer/Lilly’s Jardiance (empagliflozin) drug more than double last year to top the $1 billion threshold, with AZ hitting similar heights for its Farxiga (dapagliflozin) product.

Analysts at Evercore ISI have suggested that Jardiance could hit sales of $4 billion at its peak, driven by the results of the EMPA-REG cardiovascular outcomes study in diabetics, which showed an improvement in cardiovascular death with the drug.

Meanwhile, Farxiga has become the latest SGLT2 inhibitor to show it can reduce cardiovascular risk in type 2 diabetes last month, when AZ reported the results of the DECLARE-TIMI 58 trial, showing the drug achieved a statistically significant reduction in the composite endpoint of hospitalisations for heart failure or cardiovascular death.