EMA cracks down on JAK inflammatory disease drugs

 More than one year after the FDA’s dreaded boxed warning addition and treatment line demotion, the JAK inhibitor class of inflammatory disease drugs has gotten its uses restricted on the other side of the pond by European regulators as they too cite safety concerns.

The European Medicines Agency’s (EMA's) safety committee has recommended limiting a group of oral JAK inhibitors’ use in certain at-risk patients unless no other suitable treatment alternatives are available. AbbVie’s Rinvoq, Pfizer’s Cibinqo and Xeljanz, Eli Lilly’s Olumiant and Gilead Sciences’ Jyseleca are included in the decree, and their labels will be updated accordingly.

The EMA reached the new restriction after a safety review launched in February. It comes as new postmarketing data have linked Xeljanz to increased risks of heart-related problems and cancer compared with TNF-alpha inhibitors like AbbVie’s Humira in rheumatoid arthritis.  

Specifically, the EMA now asks that these JAK drugs not be used in patients aged 65 years or above, those already bearing risk factors of major cardiovascular problems such as heart attack or stroke, those who smoke or have smoked for a long time and those with higher risk of cancer. Exceptions can be made when the patient has exhausted treatment options.

The EMA’s safety committee also recommends that JAK inhibitors be used “with caution” in patients with risks for blood clots in the lungs and in deep veins. In the case that a JAK drug is used in those at-risk patients, the EMA suggests doses should be reduced.

Although the review was conducted based on Xeljanz’s safety findings in rheumatoid arthritis, the EMA has applied the restrictions to all approved uses of JAK inhibitors in chronic inflammatory disorders. Novartis and Incyte’s Jakvi—known as Jakafi in the U.S.—and Bristol Myer Squibb’s Inrebic, which are for the bone marrow disorder of myelofibrosis, are not part of the scrutiny. Olumiant’s emergency authorization for the short-term treatment of COVID-19 is also not included.

For procedural purpose, the safety committee’s recommendation is now headed to the drug reviewers at the EMA’s Committee for Medicinal Products for Human Use, which will issue a legally binding decision to be adopted by the European Commission.

Before the EMA move, the U.S. FDA last year added its own safety measures targeting the JAK drugs, limiting their use to patients who’ve tried but failed on at least on TNF blocker. U.S. regulators also revised the drugs’ boxed warnings, which now carry information about increased risks of serious heart-related events, cancer, blood clots and death.

At that time, analysts pointed to the European market, suggesting a better commercial environment without the extra safety alerts. Being relegated to later line of treatment doesn’t mean much detriment to JAK drugs’ sales potential in certain indications such as inflammatory bowel disease and psoriatic arthritis but could be a pain in bigger uses in rheumatoid arthritis and atopic dermatitis, analysts figured.

Compared with the EMA’s policy, the FDA version applies to all patients regardless of risk factors such as age and existing conditions. But the FDA is pushing the JAKs to treatment behind only one TNF inhibitor, while the EMA is asking those at-risk individuals try everything else before taking a JAK.

But in a surprise move by the FDA, the U.S. agency also slapped a similar warning on Incyte’s topical Opzelura cream, which shares the same ruxolitinib active ingredient as Jakafi. Opzelura is not yet approved in Europe.

After the FDA clampdown, Pfizer witnessed sharp sales declines of Xeljanz. In the first half of 2022, sales from the first-in-class JAK inhibitor plummeted 29% to $802 million, with the U.S. market contributing to the lion’s share of the decline.

In contrast, Rinvoq has been doing relatively well. AbbVie just reported Rinvoq sales had jumped 54% in the third quarter to $695 million, which brought continues to a nine-month total of $1.75 billion. AbbVie has argued that its Rinvoq shouldn’t be put under the same lens as Xeljanz because the safety findings were indeed from the Pfizer drug.

https://www.fiercepharma.com/marketing/ema-cracks-down-jak-inflammatory-disease-drugs-limiting-abbvies-rinvoq-and-more-safety