FDA boxed warning for AbbVie’s JAK inhibitor clouds Gilead’s

• The Food and Drug Administration’s decision to approve a new rheumatoid arthritis treatment with a boxed safety warning could limit the potential for the entire drug class, one Wall Street analyst cautioned in a Sunday note to investors.
• On Friday, the FDA cleared AbbVie’s Janus kinase inhibitor upadacitinib, but stipulated the drug’s labeling carry prominent mention of the risk of thrombosis — a warning that is “likely to limit the overall market size of JAK inhibitors,” SVB Leerink analyst Pasha Sarraf wrote.
• The boxed warning could have implications for Gilead and Galapagos, which together have billion-dollar sales hopes for filgotinib, an experimental JAK inhibitor they expect to file for U.S. approval by year’s end. Multiple sell-side analysts now anticipate filgotinib will receive a similar safety warning as AbbVie’s drug, called Rinvoq.

The JAK inhibitor class has excited biopharma companies, investors and physicians with clinical results that promise arthritis patients effective and more convenient treatment. But concerns the drugs increase rates of thrombosis and embolisms have resulted in safety warnings from the FDA.

Those worries are compounded by unclear scientific explanations for why these drugs may increase blood clotting, which generally occurred rarely in clinical testing of JAK inhibitors.

“In effect, there is a scientific and clinical vacuum,” SVB Leerink’s Sarraf wrote on the uncertainty. “In this vacuum, the FDA has chosen to be careful with caution to physicians.”

AbbVie’s Rinvoq (upadicitinib) is the third JAK inhibitor to gain U.S. approval in rheumatoid arthritis, following Pfizer’s Xeljanz (tofacitinib) and Eli Lilly’s Olumiant (baricitinib). All three drugs are taken orally, in contrast to the many injectable drugs commonly used for rheumatoid arthritis.

All three also have black box warnings, the FDA’s strictest possible warning. While Xeljanz and Olumiant both featured warnings specific to those drugs, Rinvoq’s warning included a more general description of the thrombotic risks.

Analysts at Cantor Fitzgerald, RBC Capital Markets and Credit Suisse each wrote in research notes that filgotinib, if approved, would likely carry a warning similar to Rinvoq’s.

SVB Leerink’s Geoffrey Porges pointed out the FDA put a warning on Rinvoq’s label even though the drug showed lower rates of venous thromboembolic events than placebo and Humira (adalimumab) in late-stage studies.

“While such class labeling does limit Rinvoq’s commercial opportunity, we now expect the whole JAK class, including the much-anticipated ‘safer JAK inhibitor’ filgotinib, to receive similar labeling,” Porges wrote in a Sunday research note.

Gilead and Galapagos are discussing with the FDA whether filgotinib can avoid a thrombosis warning, Cantor Fitzgerald analyst Eliana Merle wrote Monday. The companies recently stated plans to file filgotinib to the FDA by the end of 2019, setting up a potential market launch in 2020.

Black box language for JAK inhibitors in rheumatoid arthritis

COMPANY	DRUG	BLACK BOX LANGUAGE ON THROMBOSIS
PFIZER	Xeljanz	“Rheumatoid arthritis patients with at least one cardiovascular (CV) risk factor had a higher rate of all-cause mortality and thrombosis with Xeljanz 10 mg twice daily vs. 5 mg twice daily or TNF blockers.”
ELI LILLY	Olumiant	“Thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis, some fatal, have occurred in patients treated with Olumiant. Patients with symptoms of thrombosis should be evaluated promptly.”
ABBVIE	Rinvoq	“Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with Janus kinase inhibitors used to treat inflammatory conditions.”

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