FDA pulls J&J's Invokana boxed warning after reviewing amputation risks—but the sales damage is done

Sales of Johnson & Johnson’s diabetes drug Invokana have suffered since the FDA slapped a boxed warning on its label detailing the product’s amputation risks. But in an about-face, the agency now says it’s removed that warning.

The FDA this week scrapped the boxed warning—which has graced Invokana’s label since 2017—after reviewing data from three clinical trials, it said in a drug safety memo.

Its reasoning was twofold: For one, while Invokana did elevate risks in trials, the FDA found on its second look that the risk was “lower than previously described,” particularly when patients are “appropriately monitored,” it said.

And for two, it’s all about risk-benefit, the agency noted—and thanks to more recent data showing Invokana can help the heart and kidneys, the amputation risks no longer outweigh the drug’s “significantly enhanced benefit.”

That’s not to say the amputation threat won’t appear on Invokana’s label at all. It’ll still be described in the “Warnings and Precautions” section of the med’s prescribing info, the FDA said.

J&J’s Janssen unit, for its part, said it was “pleased with the FDA’s recognition of the important benefits Invokana brings to people living with Type 2 diabetes.”

“At Janssen, we have always been confident in the overall safety profile of Invokana,” it said in a statement, adding that it believes “these prescribing information changes appropriately communicate the safety and efficacy profile of this treatment for patients.”

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While the move represents a major obstacle out of the way for Invokana, plenty of damage has already been done to the drug’s sales over the last few years. The product, which competes against Boehringer Ingelheim and Eli Lilly’s Jardiance and AstraZeneca’s Farxiga in the SGLT2 class, has seen its revenue haul shrink by nearly half since peaking since 2016.

That year—the last full year of sales before the boxed warning—Invokana drummed up $1.41 billion, a tally that’s steadily shrunk over the last few years to reach just $735 million in 2019.

J&J can’t necessarily blame the entire slide on the warning, though. In late 2016, rival Jardiance added its ability to lower patients’ cardiovascular death risk to its label, marking the first heart-helping indication for the class and giving it a boost over its competition.

Since then, Invokana has gone on to win a couple label expansions of its own. In 2018, it nabbed clearance to reduce the combined risk of heart attack, stroke or CV death in high-risk Type 2 diabetes patients; it followed up in 2019 with a go-ahead for lowering the risk of kidney disease, worsening kidney function, CV death and hospitalization for heart failure in certain patients with Type 2 diabetes and diabetic kidney disease.

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Competition is still mounting, though, with Jardiance and AstraZeneca’s Farxiga—now the class’ sales leader—chasing kidney indications of their own.

In March, the FDA granted Jardiance a speedy review as a treatment for reducing kidney disease progression and cardiovascular death in patients with chronic kidney disease. And last month, Farxiga hit its primary endpoint of decreased kidney function, end-stage kidney disease and cardiovascular death in a pivotal phase 3 trial for chronic kidney disease patients.