Advisory Committee Gives Mixed Review to JAK Inhibitor Expected to Challenge Humira

Yesterday, the FDA’s Arthritis Advisory Committee convened for a vote on whether to recommend approval of Eli Lilly’s baricitinib, a Janus kinase (JAK) inhibitor that the company hopes to sell as Olumiant for the treatment of rheumatoid arthritis (RA). The advisory committee voted in favor of recommending approval of a dose of 2 mg and against recommending approval of a higher 4-mg dose because of concerns about safety, including the risk of thrombosis.

While the FDA’s briefing document for the committee meeting said that the agency’s review team agreed that Eli Lilly’s data demonstrated the efficacy of the proposed drug at both doses, it had lingering concerns about safety and noted that many adverse events (AEs) associated with baricitinib appeared to be dose-dependent. Because Eli Lilly’s trial design for baricitinib, limited safety data for the 2-mg dose complicated the benefit/risk assessment of the lower dose.

"While we are disappointed with the Advisory Committee's assessment of the data for the 4-mg dose, we are confident in the positive benefit—risk profile of both the 2-mg and the 4-mg doses. We look forward to continuing our work with the FDA on our New Drug Application and are hopeful that baricitinib will receive approval in the coming months,” Christi Shaw, MBA, president of Lilly Bio-Medicines, said in a statement.

Baricitinib had been widely believed to have blockbuster potential in the RA space, given the fact that it outperformed adalimumab (Humira) in terms of patient-reported outcomes in a phase 3 study, and has an oral route of administration (while anti—tumor necrosis factor biologics and biosimilars must be infused or injected). With biosimilars for the top-selling Humira not expected to launch in the United States until 2023, baricitinib could, if approved, exert pressure on Humira.

While the advisory committee’s assessment came as a disappointment for Eli Lilly, this week’s vote is not the first such setback for baricitinib; the FDA issued a Complete Response Letter for baricitinib in April 2017 after concerns about safety. In fact, JAK inhibitors as a class have come under scrutiny for their safety profiles; a recent systematic review of the FDA’s Adverse Event Reporting System found elevated reporting for thromboembolic AEs for 2 approved JAK inhibitors, tofacitinib (Xeljanz) and ruxolitinib (Jakafi), raising the question of whether a class-wide safety issue might exist for JAK inhibitors.