The FDA’s safety review of the approved Pfizer anti-inflammatory drug has been completed, and the conclusion is rippling across the entire drug category because the agency requires Additional warning Regarding the risk of serious adverse events, some of them can be fatal.
The focus of the review is Xeljanz, which is the first drug approved for the treatment of rheumatoid arthritis (RA). Pfizer’s drug is a small molecule that blocks the Janus kinase (JAK) enzyme, a family of enzymes that plays a role in cell signaling in inflammatory diseases and cancer. Xeljanz’s blocking of JAK enzymes can solve an overactive immune system, but this method can also cause other problems, such as blood clots, decreased anti-infection ability, and even cancer. These warnings are marked on the drug label.
When the FDA initially approved Xeljanz in 2012, regulators asked Pfizer to conduct an additional study to further evaluate cardiovascular problems, cancer, and infections in rheumatoid arthritis patients 50 years and older with at least one cardiovascular risk factor risk. The open-label study recruited 4,362 volunteers who were randomly assigned to receive one of two doses of Xeljanz or a tumor necrosis factor (TNF) blocker, an older drug used to treat arthritis. The two main goals of the study are to evaluate major adverse cardiovascular events and cancer.
According to the FDA’s report, the two Xeljanz groups had an increased risk of death, cardiovascular problems, cancer, and blood clots compared with the group of patients treated with TNF blockers. The risk of cancer is also higher. The FDA stated that the incidence of lymphoma and lung cancer was higher in the two Xeljanz groups compared to the TNF group. These risks are especially obvious among current or past smokers.
Since Xeljanz was first approved, the drug has won additional regulatory approvals for the treatment of psoriatic arthritis, ulcerative colitis, and a type of arthritis that develops in children and adolescents. According to the company’s 2020 annual report, among all approved indications, Pfizer’s drug sales last year exceeded $2.4 billion. Other FDA-approved JAK inhibitors include Eli Lilly’s Olumiant and AbbVie’s Rinvoq-both of which are rheumatoid arthritis drugs. Like Xeljanz, Lilly and AbbVie drugs carry a black box warning, which is the strictest and most prominent warning that the FDA can put on a drug label. The FDA said on Wednesday that it now requires label changes to further remind clinicians and patients to consider the risks and benefits of JAK inhibitors.
“Olumiant and Rinvoq have not been studied in trials similar to Xeljanz’s large safety clinical trials, so the risks have not been fully assessed,” the FDA said. “However, because they share the mechanism of action with Xeljanz, the FDA believes that these drugs may have risks similar to those seen in Xeljanz’s safety trials.”
To ensure that the benefits of these drugs outweigh the risks to patients taking them, the FDA further restricts the approved use of these drugs to patients who do not respond to or cannot tolerate TNF blockers.
Two other JAK inhibitors, Jakafi from Incyte and Inrebic from Bristol Myers Squibb, are used to treat blood diseases. Because they are not approved for use in arthritis and other inflammatory diseases, the FDA stated that they are not included in the prescribing information updates required to cover JAK inhibitors from Pfizer, AbbVie, and Eli Lilly. But the FDA added that Jakafi and Inrebic will need to update their labels differently.
It is not clear what the update means for the JAK drug application that is still under review by the FDA. The regulatory decision of Pfizer’s drug abrocitinib to treat atopic dermatitis has been postponed twice this year.Earlier this week, the clinical data reported by the pharmaceutical giant showed that small molecules Defeat Regeneron Pharmaceuticals’ blockbuster drug Dupixent in a head-to-head study of atopic dermatitisPfizer is also waiting for the FDA to approve the extension of Xeljanz’s approval to include ankylosing spondylitis, an inflammation that affects the spine.
Rinvoq was first approved in 2019 and brought AbbVie $731 million in sales last year.The pharmaceutical giant based in Illinois wait Regulatory decision on extending the scope of Rinvoq’s approval to moderate to severe atopic dermatitis. Olumiant was developed by partners Incyte and Lilly and sold by Eli Lilly, with sales of $639 million last year.Lilly and Incyte are also waiting for regulators to add Moderate to severe atopic dermatitis As an approved indication.
Photo courtesy of FDA
