Following Pfizer’s recent announcement of co-primary endpoint results from ORAL Surveillance (NCT02092467) in rheumatoid arthritis (RA) patients with cardiovascular (CV) risk factors;

Rose Joachim, Pharma Analyst at GlobalData, a leading data and analytics company, offers her view:

“These results signal troubles ahead for Xeljanz and potentially other JAK inhibitor products. The ORAL Surveillance trial first came under scrutiny in early 2019, when Pfizer had to modify the protocol mid-study due to associations between the 10mg twice daily dose of Xeljanz and higher risk of thrombosis and overall mortality. Despite a lack of safety signals with the 5mg twice daily dose at that time, some key opinion leaders interviewed by GlobalData cautiously chose to limit use of Xeljanz in RA patients with CV risk factors. This appears to have been a good judgement call.

“Working with the FDA and other regulatory agencies, Pfizer will need to do some serious damage control and try to pinpoint the specific level of cardiovascular risk associated with these negative safety outcomes. This evaluation will likely lead to an even lengthier black box warning that elaborates on malignancy and MACE risks. Prior to release of these new data, GlobalData forecast that global Xeljanz sales in RA would fall approximately 12% between 2019 and 2024, due to competition from new JAK inhibitors such as AbbVie’s Rinvoq. This recent strike against Xeljanz’s safety will likely further diminish the drug’s market share in the years leading up to patent expiry.

“While trouble for Xeljanz could mean less competition for other JAK inhibitors, it is more likely that the entire drug class will now be subject to added scrutiny. For example, in the US, following the 2019 announcement of Xeljanz’s elevated thrombosis risk, JAK inhibitors received a class-wide black box warning highlighting this potential risk. These new data may push the FDA and other regulatory authorities to request JAK inhibitor developers to perform similar cardiovascular safety studies. This inquiry may lead physicians to be warier of JAK inhibitors in general.

“There is some hope in the field that JAK1-specific inhibitors, such as AbbVie’s Rinvoq and Gilead/Galapagos’s Jyseleca, may have lower safety risks compared to multi-JAK inhibitors, such as Xeljanz. If either of these products can demonstrate improved safety in this vulnerable population, it would certainly provide them with a strong competitive edge.”