After the FDA finalized its review of safety risks for oral JAK inhibitors, it’s now ready to sign off on several inflammatory disease applications that had been delayed—only with unfavorable use restrictions.
The FDA has approved AbbVie’s Rinvoq in psoriatic arthritis and Pfizer’s Xeljanz for active ankylosing spondylitis. Both uses are restricted to patients who can’t tolerate or don’t respond well to one or more TNF inhibitors, such as AbbVie’s Humira.
The limitations aren’t really a surprise. Just a few days ago, the FDA updated the drugs’ labels, asking patients to go through TNF blockers first before taking the newer JAK inhibitors in their already-approved indications such as rheumatoid arthritis. At that time, industry watchers figured the same requirement would be applied to any future indications.
The extra caution around JAK inhibitors stems from a postmarketing study of Xeljanz which linked the drug to an increased risk of blood clots, heart-related safety events and cancer over traditional TNF drugs. After investigating, the FDA slapped classwide warnings reflecting those findings on the labels for Xeljanz, Rinvoq and Eli Lilly’s Olumiant. It also postponed several decisions in the drug class.
Rinvoq’s new psoriatic arthritis approval is based on two phase 3 trials that showed the drug better improved joint symptoms, physical function and skin manifestations than placebo did. It also showed numerically higher responses related to spinal involvement over Humira.
For its part, Xeljanz also topped placebo at triggering better responses on a spondyloarthritis scale in a phase 3 trial.
Psoriatic arthritis and ankylosing spondylitis are relatively small indications for the JAK meds. Because TNF inhibitors and IL-17 inhibitors such as Novartis’ Cosentyx and Eli Lilly’s Taltz already work pretty well for those patients, experts have expected to use the JAKs in later lines of treatment regardless of FDA restrictions, SVB Leerink analyst Geoffrey Porges wrote in a September note.
By comparison, the large atopic dermatitis indication is where industry watchers are dialed in. Before the JAK safety fallout, AbbVie expected more than $8 billion in Rinvoq sales in 2025, with $2 billion coming from atopic dermatitis. There, Porges has projected the same restriction to post-TNF use—or even behind Sanofi’s blockbuster Dupixent—for Rinvoq and other JAK drugs. Besides Rinvoq, Lilly’s Olumiant and Pfizer’s follow-on JAK candidate Cibinqo are also awaiting FDA decisions on their eczema applications.
For both rheumatoid arthritis and psoriatic arthritis, Rinvoq is only used in a 15 mg dosing strength. But it was really 30 mg Rinvoq that got analysts excited, given that it topped Dupixent on skin symptoms in a phase 3b atopic dermatitis trial.
But Porges isn’t sure whether AbbVie can get a high dose of Rinvoq approved in eczema. An approval of the apparently more efficacious high dose would give Rinvoq an efficacy edge over standard of care, whereas the low dose only offers an option similar to existing treatments, he said.
Mizuho analyst Vamil Divan has similar concerns. In a recent note to clients, Divan said he expects the low dose of Rinvoq to be approved by the FDA for eczema. But he argued the AbbVie drug’s commercial opportunity in the indication will be limited by the safety questions, “especially given how comfortable most dermatologists are with Dupixent.”