Following EMA, FDA restricts use of high-dose Xeljanz, warning of added risks for the blockbuster JAK
The FDA has come out with new restrictions on the use of Pfizer’s high-dose version of Xeljanz after researchers drew a direct line between the 10 mg dose and a higher risk of blood clots and death.
In a new safety warning out today, the agency added a boxed warning for the blockbuster JAK inhibitor, advising physicians of the risk and ordering them to restrict the approved 10 mg dose for ulcerative colitis to “certain patients who are not treated effectively or who experience severe side effects with certain other medicines.”
Though it wasn’t approved for rheumatoid arthritis, researchers had been using the 10 mg dose in a study for RA when they spotted the dangerous imbalance in outcomes, which alarmed regulators on both sides of the Atlantic. In Europe, the 10 mg dose is now banned among patients with heart failure, cancer, as well as an identifiable risk of developing blood clots.
The new restrictions follow the 2018 OK on UC, its third indication following the 2012 approval for rheumatoid arthritis and a 2017 OK for PsA.
Their notice today included this note:
The interim results of the trial, as of January 2019, have identified the following:
•19 cases of blood clots in the lung out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 3 cases out of 3,982 patient-years in patients who received TNF blockers
•45 cases of death from all causes out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 25 cases out of 3,982 patient-years in patients who received TNF blockers
The warning on Xeljanz may well have a knock-on effect at Eli Lilly, where agency concerns about Olumiant led them to steer clear of the high dose and stick with a lower dose than the company felt would be effective. You can expect the rest of the field to pay close attention as they work on rival drugs — including some therapies they hope will have a better safety profile.
Social image: Pfizer, AP Images