Eli Lilly and Incyte announced that the FDA has issued a complete response letter for the New Drug Application (NDA) of the investigational medicine baricitinib, a once-daily oral medication for the treatment of moderate-to-severe rheumatoid arthritis (RA).

The letter indicates that the FDA is unable to approve the application in its current form. Specifically, the FDA indicated that additional clinical data are needed to determine the most appropriate doses. The FDA also stated that additional data are necessary to further characterize safety concerns across treatment arms. The companies disagree with the agency's conclusions. The timing of a resubmission will be based on further discussions with the FDA.

"We are disappointed with this action. We remain confident in the benefit/risk of baricitinib as a new treatment option for adults with moderate-to-severe RA," said Christi Shaw, president of Lilly Bio-Medicines. "We will continue to work with the FDA to determine a path forward and ultimately bring baricitinib to patients in the U.S."

Lilly and Incyte submitted the NDA for baricitinib to the FDA in January 2016, and in January 2017 announced the FDA's three-month extension to allow time for review of additional data analyses.

Lilly is reaffirming both its financial guidance for 2017 and its mid-term guidance for the remainder of this decade. Incyte is evaluating the impact of the complete response on its previously-issued milestone and R&D expense guidance for 2017; any update will be provided on its Q1 2017 earnings call.

Baricitinib is a once-daily oral JAK inhibitor currently in clinical studies for inflammatory and autoimmune diseases. There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of a broad range of inflammatory conditions, including rheumatoid arthritis.

In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of baricitinib and certain follow-on compounds for patients with inflammatory and autoimmune diseases. Baricitinib was submitted for regulatory review seeking marketing approval for the treatment of rheumatoid arthritis in the U.S., European Union and Japan in 2016, and was approved in the EU in February 2017. It is being studied in phase 2 trials for atopic dermatitis and systemic lupus erythematosus, and a phase 3 trial for patients with psoriatic arthritis is expected to be initiated in 2017.

Lilly and Incyte conducted four successful pivotal phase III clinical trials of baricitinib in patients with moderate to severe active rheumatoid arthritis to support regulatory submission in most countries. Two of the four studies included pre-specified comparisons to approved DMARDs: one to methotrexate (RA-BEGIN) and one to adalimumab (RA-BEAM). An additional phase III study was initiated to support clinical development in China. The clinical trial program includes a wide range of patients including those who are methotrexate-naïve, inadequate responders to methotrexate, inadequate responders to conventional synthetic disease modifying antirheumatic drugs, or inadequate responders to biologic DMARDs including TNF inhibitors. Patients completing any of the phase III studies can enroll in a long-term extension study.