Red flag upgrade for Pfizer: FDA limits Xeljanz in colitis, slaps black box on label

Pfizer sign
Pfizer's Xeljanz has been hit with a boxed warning over potential cardiovascular risks with the 10-mg twice daily dose. (Tracy Staton)

For Pfizer’s blockbuster immunology drug Xeljanz, an FDA safety communication has now turned into a boxed warning. And forget the drug's approval as a first-line ulcerative colitis treatment, at least for now.

In a new addition to Xeljanz’s label on Friday, the FDA is warning of an increased risk of blood clots—and potentially, death—with the JAK inhibitor's 10-mg twice daily dose.

And meanwhile, the drug’s green light in ulcerative colitis has been pushed down the treatment line: It's approved only for those who do not respond to or are not suitable for other medicines.


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While the cardiovascular risks showed up in rheumatoid arthritis patients taking the 10-mg dose in a postmarketing study, the FDA argued they “may also apply to those taking [Xeljanz] for ulcerative colitis.” The 10 mg dose is only approved in UC patients.

Besides rheumatoid arthritis and colitis, Xeljanz's 5-mg twice-daily dose is also approved in psoriatic arthritis.

Pfizer first flagged the safety signal in February after an independent panel noticed higher rates of pulmonary embolism and death in RA patients taking the 10-mg regimen versus those in the 5-mg group and the TNF inhibitor control arm. The postmarketing study was designed to evaluate the risk of CV events, cancer and certain infections.

The company switched the 10-mg patients to the lower dose, and the FDA soon issued a safety communication alerting the public of the problems.

In a statement sent to FiercePharma, Pfizer said it’s still analyzing the safety information now in hand and noted that the clinical data remain blinded. “We will continue to communicate important information in a timely manner as we are able,” it said.

RELATED: FDA issues red alert on Pfizer's Xeljanz after trial tags higher dose with blood clots, death

In May, the EMA’s safety committee also put a temporary restriction on the higher dose in patients “who are at high risk of blood clots in the lungs,” including those who have heart failure or a history of blood clots, among other disorders. The temporary ban is in place until the EMA can review the available information and come up with long-term guidance, the agency said at the time.

The “boxed warning,” the FDA's most severe safety flag, could deal a blow to Xeljanz’s growth momentum. In the first quarter, its sales jumped 34% to $423 million, with 7% volume growth in ulcerative colitis, CEO Albert Bourla said during an earnings call in April.

Despite the warnings, Pfizer still expects Xeljanz will continue to grow, mainly because the 10-mg dose has never been approved in RA, its largest indication, Cantor Fitzgerald analyst Louise Chen noted in a Friday report to clients. As for being removed from the first line in UC, “Pfizer has noted that the large majority of current UC patients on Xeljanz are inadequate responders to TNFi's anyhow,” so the impact is limited, the analyst said.

It could spell more trouble as new JAK inhibitors near the market, though. AbbVie’s upadacitinib is under FDA priority review with a decision expected next month. Evaluate Pharma analysts previously estimated the drug could reach $2.18 billion in annual sales by 2024.

Meanwhile, Gilead Sciences' application for filgotinib—which carries its own potential testicular safety concerns—could be filed soon. Gilead recently said a meeting with the FDA went its way.

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