Pharma's JAK drugs could suffer in rheumatoid arthritis, atopic dermatitis. How do FDA warnings affect other inflammatory uses?

Drugs and money sign
A rheumatology industry leader expects to reduce up to one third of his use of JAK inhibitors in rheumatoid arthritis following FDA's labeling updates. (Getty/ADragan)

After the FDA last week slapped safety warnings and use restrictions on AbbVie’s Rinvoq, Eli Lilly’s Olumiant and Pfizer’s Xeljanz, Wall Street has started rethinking its calculations for the JAK inhibitor class.

Based on discussions with three industry experts, analysts with SVB Leerink believe the FDA’s warning could have a range of effects on the meds’ opportunities across inflammatory diseases.

JAKs could see big use reductions in rheumatoid arthritis in the near term, and they’re vulnerable to new competition in atopic dermatitis, the SVB Leerink analysts said in recent notes. On the other hand, inflammatory bowel disease still represents a big market for JAK inhibitors, while smaller indications such as psoriatic arthritis and ankylosing spondylitis remain unchanged, according to the team.

As one of the largest indications for JAKs, rheumatoid arthritis is already an approved use for Xeljanz, Olumiant and Rinvoq. But after Xeljanz’s post-marketing study found heart-related side effects and cancer risks, a rheumatology industry leader SVB Leerink interviewed stopped starting new arthritis patients with the Pfizer drug, even though he had “considerable experience” with JAKs and liked their strong efficacy and oral dosing.

While the expert still prescribes Olumiant and Rinvoq to new patients, he expects to reduce up to one-third of his use of JAKs in rheumatoid arthritis in general. About 10% to 15% of his current rheumatoid arthritis patients are on JAKs now. As the final labels from the FDA kick in, JAKs will mostly be used after methotrexate and other small-molecule drugs, as well as TNFs and even other biologics such as Roche’s IL-6 inhibitor Actemra, the expert said.

Nevertheless, the rheumatologist suggests JAKs may regain share three years from now as doctors get used to the labels and if no new safety signals appear. Among the three drugs, the expect prefers Rinvoq given available clinical data and marketing strategies. Rheumatoid arthritis makes up half of AbbVie’s $8 billion estimate for Rinvoq sales in 2025.

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At $2 billion in potential 2025 sales, atopic dermatitis, or eczema, represents the second-largest indication AbbVie has planned for Rinvoq. That drug, plus Olumiant and Pfizer’s investigational JAK inhibitor abrocitinib, all await FDA decisions on their eczema applications.

In eczema, Sanofi and Regeneron’s Dupixent has become the doctor's go-to option, and analysts have always been expecting JAKs’ use behind the IL-4/13 biologic. But now that the FDA has restricted JAKs’ existing uses to patients who’ve tried but failed on at least one TNF inhibitor, a dermatologist that SVB Leerink has spoken with suggested novel pipeline drugs might jump ahead of JAKs in the treatment order.

These possible new meds include IL-13 inhibitors such as Eli Lilly’s lebrikizumab, anti-OX40 agents, and others, SVB Leerink proposed.

In addition to newcomers, the FDA’s cautious view on oral JAKs’ safety profile threatens potential approvals for the meds at high doses for eczema, the dermatologist suggested. He argued the high doses are “critical to the efficacy claims” of JAKs. That’s because JAKs have topped Dupixent on efficacy markers only at the higher strengths, the SVB Leerink analysts noted.

“The dermatologist notes that atopic dermatitis has variable disease symptoms, and without the flexibility to dose higher, patients may derive inadequate control of itch and other symptoms, thus limiting JAK usefulness,” the SVB Leerink team wrote in a note last week.

Among the three JAK applications in eczema, the dermatology expert also favored Rinvoq because of its better efficacy-safety balance.

Beyond rheumatoid arthritis and eczema, inflammatory bowel disease (IBD) is another large potential market for JAKs; AbbVie’s 2025 IBD sales projection for Rinvoq is $1 billion. There, a gastroenterology specialist figured the FDA’s changes to labeling don’t affect JAK inhibitors’ advantage as oral agents, and their strong efficacy still far outweighs the potential risks.

What’s more, the doctor pointed out the safety signals from Xeljanz were from rheumatoid arthritis, where patients are typically older with more cardiovascular risk factors.

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The gastroenterologist, who works at “a large New York medical system,” said about 70% of ulcerative patients either don’t respond to TNF inhibitors or can’t remain in remission and therefore need further treatment. JAKs currently reach about 10% to 15% of IBD patients in the second-line setting and could expand to 25% to 35% in the next five years, the expert estimated.

The IBD treatment paradigm is shifting toward oral drugs, the gastroenterologist predicted. To him, the trend favors JAK inhibitors, especially AbbVie’s Rinvoq, which he suggested is “modestly differentiated” from other in-class rivals. The SVB Leerink team, more bullish on JAKs’ opportunity in IBD than AbbVie, pegged $3 billion IBD sales for Rinvoq in 2025.

As for the smaller indications of psoriatic arthritis and ankylosing spondylitis, the market opportunity for JAKs there has always been limited, the SVB Leerink team noted in a Thursday note. In these two areas, TNFs and IL-17s—mostly, Novartis’ Cosentyx and Eli Lilly’s Taltz—have been “almost universally successful,” and there was little need for JAKs, the rheumatologist that SVB Leerink interviewed observed.