JAK inhibitors from Pfizer, AbbVie and Lilly hit with dreaded FDA heart safety, cancer warnings

The safety problem for Pfizer’s arthritis drug Xeljanz has taken casualties across its drug class.

The FDA is requiring new heart safety and cancer warnings for Xeljanz, AbbVie’s Rinvoq and Lilly’s Olumiant, the agency said Wednesday. All three drugs belong to the same JAK inhibitor class of medicines, and they currently already bear boxed warnings about blood clots and lymphoma.

Thanks to the updated warnings, the FDA is pushing back the drugs’ place in the treatment sequence and is limiting their use in all approved indications to certain patients who have failed on or aren't appropriate for treatment with TNF blockers. For AbbVie's star immunology drug Rinvoq, the news prompted one influential analyst to dramatically lower his long-term sales expectations.

The FDA reached its decision after reviewing a large postmarketing study of Xeljanz that linked the Pfizer drug to an increased risk of serious heart-related side effects and cancer over traditional TNF blockers such as AbbVie’s Humira in patients with rheumatoid arthritis who have certain heart risk factors.

In this case, Olumiant and Rinvoq are suffering collateral damage. Before the FDA's ruling, industry watchers have largely been expecting a Xeljanz-exclusive limitation since other drugs haven’t shown the heart and cancer problems at the same scale in their own clinical trials. Some market watchers pointed to the European Medicines Agency’s recent go-ahead for Rinvoq in atopic dermatitis as a positive sign for the meds.

RELATED: FDA's new JAK safety restrictions spell trouble for AbbVie's Rinvoq, but to what extent?

As the FDA acknowledged, Olumiant and Rinvoq don’t have large safety trials similar to that of Xeljanz’s “so the risks have not been adequately evaluated.” 

But since Olumiant and Rinvoq “share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial,” the agency said.

In a note to clients Wednesday, Bernstein analyst Ronny Gal said his team is reducing their peak sales estimate for Rinvoq from $17.2 billion to $11.2 billion. The team expects the drug to be used after IL-23 inhibitors and other drugs in psoriatic arthritis and ulcerative colitis, and now expects lower uptake in the key atopic dermatitis indication.

For their part, Piper Sandler analysts don't see the news as negatively for AbbVie. They expect a "limited" effect from the FDA's move in the short term, and said they don't "believe all JAKs will be painted with the Xeljanz brush forever." 

RELATED: AbbVie's big Rinvoq ambitions—and the larger JAK class—face even more uncertainty with latest FDA delays

AbbVie has high hopes for Rinvoq as one of two immunology drugs to help fill in the huge revenue gap left by Humira once it loses U.S. market exclusivity. For Rinvoq's atopic dermatitis indication alone, AbbVie has pegged its 2025 sales potential at $2 billion. AbbVie's shares were down about 8% after the news on Wednesday.

Amid the FDA's JAK safety review, several drugs in the class have had label expansion reviews delayed. Those include Rinvoq’s filings in atopic dermatitis, psoriatic arthritis and ankylosing spondylitis, plus applications for Olumiant and Pfizer’s investigational abrocitinib in atopic dermatitis.

The warning doesn’t affect Incyte’s Jakafi and Bristol Myers Squibb’s Inrebic, both of which are JAK inhibitors used to treat blood disorders. The FDA is requiring other updates to their labels.