Last September, the FDA said it will require safety warnings for drugs such as Pfizer’s Xeljanz, Eli Lilly’s Olumiant and AbbVie’s Rinvoq.
Now, it’s Europe’s turn to step up its examination of the treatments. Friday, the European Medicines Agency (EMA) said its Pharmacovigilance Risk Assessment Committee (PRAC) would look at all JAK inhibitors following recent results of a clinical trial of rheumatoid arthritis drug Xeljanz, which showed recipients were more likely to experience cardio problems such as heart attack, stroke or death due to cardiovascular disease.
The trial also showed patients had a higher risk of developing cancer than patients who were treated with drugs from the TNF inhibitor class, such as AbbVie’s Humira.
Additionally, Xeljanz Study Reveals Serious Safety Concerns was linked to a higher risk of death from any cause—including infection, blood clots in the lungs and deep vein thrombosis.
RELATED: FDA weighs tighter restrictions for Pfizer’s Xeljanz on the heels of safety red flags
EMA said its decision to conduct a JAK review is in response to its preliminary look at another rheumatoid arthritis drug, Olumiant. An observational study also suggests an increased risk of major cardiovascular issues and deep vein thrombosis.
“In the treatment of inflammatory disorders, Olumiant and other JAK inhibitors work in a similar way to Xeljanz,” the EMA explained in a release. “PRAC will therefore carry out a review to determine whether these risks are associated with all JAK inhibitors authorized in the EU for the treatment of inflammatory disorders and whether the marketing authorizations for these medicines should be amended.”
Last week, the FDA said it was considering tightening its restrictions on Xeljanz after reviewing the same data. The U.S. regulator already restricts the 10 mg dose of the drug, which applies only to patients who take it for ulcerative colitis. Now, the FDA is considering limitations on smaller doses, which apply to other indications.
The regulators’ actions are in response to a trial of roughly 4,400 rheumatoid arthritis patients who were at least 50 years old and had at least one cardiovascular risk factor. The rate of major cardiovascular events was higher for Xeljanz takers at 3.37% versus 2.55% for the TNF group. Cancers developed in 4.19% of Xeljanz patients, also higher than the 2.89% among TNF recipients.
Pfizer first warned of heart-related safety issues tied to the trial’s 10-mg Xeljanz dose in 2019. The FDA took note, slapping a warning label on the drug pointing to an increased risk of blood clots and death. The EMA followed with a similar but slightly different restriction.
The restrictions and scrutiny have just begun to affect the use of Xeljanz. After years of steady growth from when it was first approved in 2012, sales of Xeljanz have leveled off. After generating (PDF) $2.44 billion in 2020, Xeljanz’s sales reached $2.45 billion in 2021.
In a quarterly conference call early this month, Pfizer said it’s too early to tell what the implications of the recent results will be.
“We still have a lot of work to do in terms of secondary endpoints, subpopulations and bringing all of this together to discuss this with regulators,” Angela Hwang, Pfizer’s biopharma president, said.
“I think we’re still a ways off in terms of really understanding what impact it will be to our label.”