Safety uncertainty forces FDA's hand on JAK inhibitors

The inclusion and wording of a black box warning for thrombosis and embolism risk in the label for upadacitinib are now likely to be applied across all JAK inhibitors used for autoimmune diseases, according to SVB Leerink Research analyst Pasha Sarraf, referring to last Friday’s approval of  AbbVie’s (NYSE: ABBV) Rinvoq (upadacitinib) by the US Food and Drug Administration.

Belgium-based Galapagos (Euronext: GLPG) has its own JAK-inhibitor, filgotinib, under development, and AbbVie once had a license option on the drug, which is now partnered with US biotech Gilead Sciences (Nasdaq: GILD).

Dr Sarraf said he has spoken to Galapagos management who believe that they can make a case based on their differentiated adverse event (AE) rates to avoid such language. Other regulatory specialists he contacted over the weekend, however, believe it is unlikely that filgotinib or other JAK inhibitors will be able to avoid such labels in the future. The proof of absence is hard to make in the real world, requiring enormous numbers of patient-years of exposure, which may be just as likely to increase the rates as decrease them, as has been seen with Pfizer’s (NYSE: PFE) Xeljanz (tofacitinib), Dr Sarraf noted.