Eli Lilly touts long-term safety data for Olumiant amid classwide scrutiny on JAK meds

Eli Lilly
Thanks to safety signals from Pfizer's rival JAK inhibitor Xeljanz, the FDA is also pushing back Olumiant's use behind TNF blockers. (Eli Lilly)

Eli Lilly’s Olumiant has been dragged into a classwide safety review of JAK medicines that originated from Pfizer’s Xeljanz. Hoping to convince doctors that its offering doesn’t share the problems at the same magnitude, the Indianapolis pharma is turning to long-term data.

A pooled analysis across nine clinical trials—and one long-term extension study—in rheumatoid arthritis patients who received Olumiant for up to 9.3 years found that the Lilly drug maintained a similar safety profile to earlier trial results, the company unveiled at the American College of Rheumatology’s virtual annual meeting.

The new analysis comes as Olumiant faces a classwide boxed warning detailing increased risks of serious heart-related events, cancer, blood clots and death. The FDA’s move to implement the warning came after a postmarketing study of Xeljanz linked the Pfizer med to increased heart safety and cancer risks compared with old-school TNF inhibitors.

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In the new pooled analysis, the incidence of major adverse cardiovascular events (MACE) for Olumiant was 0.51 per 100 patient-years of exposure, which Lilly said falls within the range in the general rheumatoid arthritis population as described in epidemiological studies. The analysis covered 3,770 patients taking Olumiant at 4 mg and 2 mg doses for a median of 4.6 years.

In a subgroup of patients over 50 years old who had at least one existing heart risk factor, the incidence rate of MACE was higher at 0.77 per 100 patient-years.

That latter patient population was targeted in Pfizer’s postmarketing safety study for Xeljanz. As the New York pharma disclosed earlier this year, Xeljanz’s MACE incidence rate was 0.91 per 100 person-years at the 5 mg dose, compared with 0.73 for TNF blockers. The difference translated into an increased risk of 24% for Xeljanz.

As for the cancer rates, the age-adjusted number for Olumiant was 0.92 per 100 person-years, which Lilly again said appeared similar to the general U.S. population. In the Pfizer trial, Xeljanz recorded a cancer rate of 1.13, compared with 0.77 for TNF inhibitors.

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Oral JAK inhibitors already carry black-boxed warnings highlighting risks of cancer and blood clots. But after reviewing the updated Xeljanz data, the FDA in September said it’s requiring new heart safety and cancer warnings for all three oral JAK inhibitors in inflammatory diseases. In a more damaging move, the FDA is also pushing back the drugs’ place in the treatment order behind TNF blockers. Besides Xeljanz, Olumiant and AbbVie’s Rinvoq were included because the FDA believes they may have similar risks given their shared mechanism of action.

The FDA has yet to finalize the specific wording for the updated JAK labels, but a rheumatologist SVB Leerink analyst Geoffrey Porges spoke with after the agency’s announcement suggested a significant reduction in JAK use in rheumatoid arthritis. The expert figured doctors will likely use JAKs after small-molecule drugs, TNFs, and more frequently also after IL-6 inhibitors such as Roche’s Actemra.

Nevertheless, he expected the JAK inhibitors could regain share three years from now if no new safety concerns emerge.

Meanwhile, as the FDA mulls over the language of JAK labels, the agency has delayed its decisions on several JAK indication expansion applications, including Lilly’s bid to move Olumiant into atopic dermatitis.

Editor's Note: There was a typo in an earlier version of the story that mistakenly labeled Actemra as an IL-5 inhibitor. It's actually an inhibitor of the IL-6 receptor.