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

The FDA raised a red flag Monday on Pfizer's immunology drug Xeljanz after study data drew potential links between its higher, 10mg dose and life-threatening or fatal blood clots.

In a safety communication, the agency highlighted Pfizer's decision last week to move rheumatoid arthritis trial patients taking 10mg of Xeljanz twice daily to the twice-daily 5mg dose. Early data from that trial suggested that patients on the higher dose were more likely to suffer pulmonary embolism—blood clots in the lungs that can be fatal—or die.

The Pfizer drug isn't the only one in its class of JAK inhibitors to run into dose-related safety worries. Eli Lilly only won a green light for the lower dose of Olumiant after study data flagged a risk of serious blood clots. Olumiant was approved with a black-box warning citing those risks.

The Xeljanz postmarketing safety study—which the FDA required when it approved Xeljanz for RA back in 2012—will continue, the agency said. The FDA is “working with the manufacturer to evaluate other currently available safety information” for Xeljanz and would “update the public with any new information based on our ongoing review.”

RELATED: Does Pfizer's Xeljanz share its CV safety questions with burgeoning JAK class?

In the meantime, the FDA told healthcare professionals to follow Xeljanz’ prescribing information for the specific condition they are treating. The 10 mg dose in question isn’t approved for rheumatoid arthritis patients; it is, however, greenlighted in ulcerative colitis patients.

“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

The Xeljanz trial—which was meant to evaluate the risk of cardiovascular events, cancer and certain infections—first made headlines last week when Pfizer said it was moving all study patients receiving the 10 mg dose onto the 5 mg dose. The study enrolled only RA patients who were at least 50 years old and had at least one cardiovascular risk factor.

RELATED: Pfizer switches RA patients to lower dose of fast-growing Xeljanz as safety issues arise in postmarketing study

The Xeljanz alarm bell follows Olumiant's own dose-related problems. In March 2017, the FDA rejected the Lilly drug on its first attempt at approval, citing a need for more data “to determine the most appropriate doses” and to “further characterize safety concerns across treatment arms."

When Olumiant came back up for FDA review last year—looking for approval for two different doses—the agency's expert advisers refused to back the higher dose. The FDA ended up approving only the lower dose, and then only with the black-box warning.

The agency is now reviewing AbbVie's entrant into the class, upadacitinib, and Gilead Sciences' JAK inhibitor, filgotinib, is moving its way up the pipeline. Upadacitinib's phase 3 data turned up a hemorrhagic stroke death and a pulmonary embolism, both in patients the pharma says had “pre-existing cardiovascular risk factors."

The Gilead drug, partnered with Galapagos, could have a safety edge, analysts say; serious clot risks so far haven't surfaced in its trials.