Type of information: Submission of an NDA
Product name: Olumiant®
Compound: baricitinib (LY3009104)
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
- kinase inhibitor/tyrosine kinase inhibitor/janus kinase inhibitor. Baricitinib is a once daily, oral, selective JAK1 and JAK2 inhibitor. 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. Baricitinib demonstrates approximately 100-fold greater potency of inhibition against JAK1 and JAK2 than JAK 3 in kinase assays.
- 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 is currently in Phase 3 clinical development for rheumatoid arthritis and Phase 2 development for psoriasis and diabetic nephropathy.
- Lilly and Incyte conducted four pivotal Phase 3 clinical trials of baricitinib in patients with moderately-to-severely active rheumatoid arthritis to support regulatory submission in most countries. An additional Phase 3 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 disease-modifying anti-rheumatic drugs, or inadequate responders to TNF inhibitors. Patients completing any of the five Phase 3 studies can enroll in a long-term extension study.
Company: Eli Lilly (USA -IN) Incyte Corporation (USA - DE)
Disease: rheumatoid arthritis
- • On August 30, 2017, Eli Lilly and Incyte announced that, after discussions with the FDA in late August, Lilly will resubmit the New Drug Application (NDA) for baricitinib before the end of January 2018. The resubmission package will include new safety and efficacy data. The companies anticipate the FDA will classify the application as a Class II resubmission, which will start a new six-month review cycle.
- • On July 25, 2017, Eli Lilly announced that a resubmission to the FDA for the New Drug Application (NDA) for baricitinib for the treatment of moderate-to-severe rheumatoid arthritis will be delayed beyond 2017. The companies will be further discussing the path forward with the agency and evaluating options for resubmission, including the potential for an additional clinical study, as requested by the FDA . The agency has indicated that a new clinical study is necessary to further characterize the benefit/risk across doses, in light of the observed imbalance in thromboembolic events that occurred during the placebo-controlled period of the rheumatoid arthritis clinical program. This request for an additional clinical study does not impact the ongoing clinical trials for baricitinib.
- The length of time to a resubmission for the NDA will depend on which option the companies pursue and further FDA discussions, but is anticipated to be a minimum of 18 months.
- In the European Union , where baricitinib 2-mg and 4-mg tablets have been approved since February 2017 , the CHMP recently agreed to update the label with a precaution for patients who have risk factors for deep venous thrombosis and pulmonary embolism. In Japan , where baricitinib was also recently approved, the label includes a similar precaution.
- • On July 3, 2017, Eli Lilly and Incyte announced that Japan's Ministry of Health, Labor and Welfare (MHLW) granted marketing approval for Olumiant® (baricitinib) 2-mg and 4-mg tablets for the treatment of rheumatoid arthritis (including the prevention of structural injury of joints) in patients with inadequate response to standard-of-care therapies. The approval is based on the results of the baricitinib development program, which includes four phase 3 clinical trials enrolling various populations of more than 3,000 moderate-to-severe rheumatoid arthritis patients worldwide, including more than 500 Japanese patients. In clinical studies, baricitinib has demonstrated significant improvement in the signs and symptoms of rheumatoid arthritis compared to standard-of-care therapies.
- The Japan marketing authorization of Olumiant triggers a $15 million milestone payment from Lilly to Incyte, which Incyte expects to recognize, in full, in the third quarter of 2017.
- • On April 14, 2017, Eli Lilly and Incyte announced that the FDA has issued a complete response letter for the New Drug Application (NDA) of baricitinib, a once-daily oral medication for the treatment of moderate-to-severe rheumatoid arthritis. 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. 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.
- • On February 13, 2017, the European Commission has approved Olumiant® ( baricitinib) for the treatment of of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease modifying anti rheumatic drugs (DMARDs).
- • On December 16, 2016, Eli Lilly and Incyte announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion, recommending the approval of baricitinib. Baricitinib would be indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease modifying anti rheumatic drugs (DMARDs). Baricitinib may be used as monotherapy or in combination with methotrexate. The CHMP positive opinion was based on five phase 3 clinical trials of baricitinib in adult patients with moderate to severe active rheumatoid arthritis (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON and RA-BEYOND). A wide range of patients participated in the clinical trial program, including those who are inadequate responders to methotrexate, inadequate responders to conventional synthetic disease modifying anti rheumatic drugs (csDMARDs), or inadequate responders to biological disease modifying anti rheumatic drugs (bDMARDs) including TNF inhibitors.
- The $65 million milestone payment that was to be paid by Lilly to Incyte upon positive CHMP opinion will now be triggered by the granting of marketing authorization by the EU Commission per a recent amendment to the parties' Agreement.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
UE authorization: 2017-02-13
Favourable opinion UE: 2016-12-15
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: