The Saint schreef op 18 aug 2019 om 21:39:
There has been much speculation about how filgotinib and upadacitinib will perform against one another in terms of efficacy, safety, and mechanism of action. For Singh, this is all just talk, at least for the moment, for one simple reason: “It is impossible to compare them because they have not been stacked up head-to-head in a clinical trial,” he said.
Compare and contrast
Angus Worthing, MD, chair of the American College of Rheumatology’s Government Affairs Committee, tried to view the potential rivalry between the two drugs in a positive light. “Approval of a third JAK inhibitor could improve overall patient access to treatments,” he said.
Much ado has been made about the differences between JAK1, JAK2 and JAK3 inhibitors, according to Singh. “It is all very interesting from the perspective of a basic science discussion,” he said. “However, it does not necessarily pan out with regard to side effect profile. These differences present mesmerizing and interesting hypotheses at best.”
For Singh, the true story of the drugs will be told in phase 4 post-marketing studies. “There are a lot of claims being made by the developers that one drug is better than the other, or about the safety profiles,” he said. “This one causes an increase in thromboembolisms, that one causes gastrointestinal perforations. Most of these are unsubstantiated claims. We will see how this pans out once the drugs are in use in the real world.”
Overall, Singh noted that both JAK inhibitors have demonstrated “generally good efficacy and safety” as they have moved through the clinical trial process. “I view them as being in the neighborhood of other JAK inhibitors and biologics that we have seen,” he said. “They both appear to be good drugs.”
To that point, Worthing addressed upadacitinib in the context of AbbVie’s other flagship rheumatology drug, adalimumab. “Although upadacitinib is a small molecule JAK inhibitor that preferentially inhibits JAK1 and [adalimumab] is a monoclonal antibody to TNF, both might actually work similarly, since TNF activates intracellular JAK pathways,” he said.
Choi declined to comment on how filgotinib might perform against upadacitinib or adalimumab. She also declined to comment on whether the recent petition to the FDA signifies more steps into the rheumatology arena for Gilead.