...We have spoken to GLPG management whobelieve that they can make a case based on their differentiated adverseevent (AE) rates to avoid such language. Other regulatory specialistswe have contacted over the weekend, however, believe it is unlikelythat filgotinib or other JAK inhibitors will be able to avoid such labelsin the future. The proof of absence is hard to make in the real world,requiring enormous numbers of patient-years of exposure, which maybe just as likely to increase the rates as decrease them, as we haveseen with Xeljanz. In the view of these specialists, given the time neededto accumulate these numbers, together with the significant uncertaintyaround the occurrence of deep vein thrombosis (DVT) and pulmonaryembolism (PE) events, the FDA is unlikely to spare future JAK inhibitorswith a "clean" label. We view this as a prudent approach by the FDAgiven the danger of thrombotic events as silent killers. Furthermore,the mechanism of why these events are occurring is unclear.
...The scientific literature does not offer adequate explanationsfor why JAK inhibitors may or may not be driving increased thromboticevents, nor have other players with active programs, including GLPG,offered meaningful hypotheses on what’s going on. In effect there is ascientific and clinical vacuum. In this vacuum, the FDA has chosen tobe careful with caution to physicians. The clinical trialists we spoke withdo not pay any attention to these type of warnings, but note that generalpractitioners do. According to those specialists, however, the details ofthe adverse events tables are important and may drive their choicesfor prescribing. The ability to share this data may provide some abilityfor differentiation. We believe this safety overhang, on top of expectedand well-known concerns such as heightened infection risk and those ofmalignancy, will negatively impact the breadth and speed of JAK inhibitoruptake in the treatment of rheumatoid arthritis (RA) despite the need forbetter treatments in the space.