FDA rejects potential blockbuster, requesting further safety data.
The United States Food and Drug Administration declined to approve Olumiant (baricitinib) for the treatment of rheumatoid arthritis (RA). The drug is a collaboration between Eli Lilly and Company and Incyte Corporation, and was anticipated to be a significant financial success for the company had it been approved.
indicated that additional clinical data are needed to determine the most appropriate doses," an official release from Lilly stated. "The
also stated that additional data are necessary to further characterize safety concerns across treatment arms.
The companies disagree with the Agency's conclusions."
The drug's approval process had been pushed back already, with a three month extension issued in January. Many in the industry were, however, confident that the drug would be greenlighted today.
Baricitinib is a Janus kinase inhibitor, or JAK-inhibitor. Such drugs are believed to work by interfering with enzyme reception associated with inflammation. It would have been only the second JAK inhibitor domestically available, as Pfizer's Xeljanz (tofacitinib) had previously been approved in 2012.
Baricitinib was approved in February by the European Medicines Agency, which also recently accepted tofacitinib after years of rejecting that drug for safety concerns. Baricitinib selectively inhibits JAK1 and JAK2 over JAK3, whereas tofacitinib inhibits JAK1 and JAK3 over JAK2. “Due to different in vitro selectivity profiles against JAK family members, inhibitors within this class may have differing safety and efficacy profiles as well as other pharmacological differences,” authors of a 2015 study of baricitinib wrote.
The EMA's initial rejection of the other JAK-inhibitor, tofacitinib, cited infection risks (common with immunosuppressants) as well as “a risk of other severe side effects including certain cancers, gastro-intestinal perforations (holes in the wall of the gut), liver damage and problems with increased lipid (fat) levels in the blood.”
Baricitinib had performed well against the current RA juggernaut adalimumab (AbbVie’s Humira), a tumor necrosis factor (TNF) inhibitor, in head-to-head trials. In a yearlong study published earlier this year in The New England Journal of Medicine, positive ACR20 response rate was observed in 70% of patients on Baricitinib by week 12, compared to 61% on adalimumab. Slightly more patients from the JAK-inhibitor group withdrew by the halfway point of the study due to adverse events than from the TNF-inhibitor group (5% to 2%).
The newest set of European League Against Rheumatism guidelines for the treatment of rheumatoid arthritis reprioritized such drugs to suggest their use in the disease, typically as a treatment in patients with moderate-to-severe RA for whom other disease-modifying antirheumatic drugs (DMARDs) have failed, and often in combination with methotrexate.
Currently, several other pharmaceutical companies are working to develop their own variety of JAK inhibitor.
The FDA's somewhat surprising announcement today may delay resubmission of the drug for more than a year as Lilly and Incyte work to garner the necessary clinical data.