On 20 March 2019, the European Medicines Agency (EMA) announced that it has put Pfizer’s blockbuster JAK inhibitor drug, Xeljanz (tofacitinib), under review following signs from a post-marketing study showing an increased risk of pulmonary embolism and overall mortality in rheumatoid arthritis (RA) patients who received a 10mg dose of Xeljanz twice daily, compared to patients receiving a 5mg twice daily dose.  

Rose Joachim, Pharma Analyst at GlobalData, a leading data and analytics company, offers her view on the implications of this development on the future of Xeljanz and the growing JAK inhibitor class:

“Considering that the cardiovascular risks of JAK inhibitors have long been on the radar of regulatory agencies, GlobalData does not think that Xeljanz’s new cardiovascular safety signal will greatly impact the evaluation of novel JAK inhibitor candidates like AbbVie’s upadacitinib or Galapagos’ and Gilead’s filgotinib.

“However, this event does further raise the stakes for companies to develop a JAK inhibitor that lacks these safety issues. For example, if filgotinib continues to show the safety profile it did in its first completed Phase III trial, it could be a powerful differentiator for the product.

“This recent communication by the EMA appears to be in line with the Drug Safety Communication released by the FDA in late February. The regulatory agencies are scrutinizing Pfizer’s ongoing post-marketing study and urging physicians to carefully monitor patients on Xeljanz for signs of pulmonary embolism, but do not yet feel the need to put limits on dosing.

“While this approach seems logical for patients with RA and other diseases in which the approved dose of Xeljanz is 5mg twice daily, it is interesting that the FDA and now the EMA remain unfazed by the treatment of patients with ulcerative colitis (UC) using the approved 10mg dose. It appears that the EMA and FDA are confident that at the approved doses, the benefits of JAK inhibitors like Xeljanz outweigh the risks.”