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Clinical Trials

Date: 2016-06-09

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the Annual European Congress of Rheumatology (EULAR 2016) in London

Company: Eli Lilly (USA - IN) Incyte Corporation (USA - DE)

Product: baricitinib (LY3009104)

Action mechanism:

  • 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 are conducting 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. Four of these five pivotal studies are expected to be completed by the end of 2015. Patients completing any of the five Phase 3 studies can enroll in a long-term extension study.

Disease: rheumatoid arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: Argentina, Austria, Belgium, Brazil, Canada, Germany, Greece, India, Italy, Japan, Republic of Korea, Mexico, Portugal, Puerto Rico, Russian Federation, South Africa, Sweden, UK, USA

Trial details:

  • The purpose of the RA-BEGIN study is to determine whether baricitinib therapy alone is noninferior to methotrexate (MTX) therapy alone in the treatment of moderate to severe active rheumatoid arthritis (RA) in those who have had limited or no treatment with MTX and are naive to other conventional or biologic disease-modifying antirheumatic drugs (DMARDs). The RA-BEGIN study included patients who had limited or no prior treatment with methotrexate, and were naïve to other conventional or biologic DMARDs. Part of a larger phase 3 program of more than 3,000 rheumatoid arthritis patients at various points in the RA treatment continuum, RA-BEGIN enrolled nearly 600 patients who were randomized to one of the following treatment groups: once-weekly oral methotrexate monotherapy, 4 mg once-daily oral baricitinib monotherapy, 4 mg once-daily oral baricitinib in combination with once-weekly oral methotrexate. (NCT01711359)

Latest news:

  • • On June 9, 2016, Eli Lilly and Incyte announced that in two phase 3 trials patients with rheumatoid arthritis treated with baricitinib reported significant improvements in quality of life symptoms and other patient-reported outcomes compared to methotrexate or adalimumab (Humira®). Patients with rheumatoid arthritis also reported improvement in productivity at work. In these studies, significant improvements in patient-reported measures, including pain, physical function, tiredness and morning joint stiffness, were observed as early as one week after initial treatment with baricitinib. These findings were presented  at the Annual European Congress of Rheumatology (EULAR 2016) in London. In the phase 3 RA-BEGIN trial: At 24 weeks, 81 percent of patients receiving baricitinib monotherapy and 79 percent of patients receiving baricitinib plus methotrexate had clinically meaningful improvement in physical function compared with 70 percent among those receiving methotrexate alone (p < 0.05). Clinically meaningful improvement was defined as an improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) score of =0.22. At 52 weeks, 68 percent of patients on baricitinib monotherapy and 72 percent of patients on baricitinib in combination with methotrexate saw clinically meaningful improvements in physical function compared to 57 percent of those treated with methotrexate alone (p < 0.05). At 24 and 52 weeks, baricitinib (as monotherapy or in combination with methotrexate) was also associated with significant improvement in pain, and clinically meaningful improvement in fatigue and the physical health components of the quality of life assessment compared with methotrexate alone. RA-BEGIN demonstrated that in rheumatoid arthritis patients who had limited or no previous treatment with any disease-modifying antirheumatic drugs (DMARDs), baricitinib used as monotherapy or in combination with methotrexate showed statistically significant improvements in the physical quality of life measures, as measured by the SF-36, when compared to methotrexate alone. Reported improvements in patient quality of life symptoms were accompanied by an increase in physical function, and decreased pain and fatigue. All the improvements with baricitinib were statistically significant at week 24 and week 52, compared to methotrexate alone.
  • • On November  7, 2015, Eli Lilly and Incyte announced detailed data from the pivotal phase 3 RA-BEGIN study, which show investigational baricitinib alone and in combination were superior to methotrexate monotherapy in helping patients achieve clinical remission. Findings will be shared at the American College of Rheumatology /Association of Rheumatology Health Professionals annual meeting in San Francisco, revealing superiority for investigational therapy baricitinib over methotrexate in improving multiple measures of the signs and symptoms of rheumatoid arthritis. Lilly and Incyte previously announced that the study met its primary objective of demonstrating the non-inferiority of baricitinib monotherapy to methotrexate monotherapy based on ACR20 response rate after 24 weeks of treatment. Additionally, it was announced that baricitinib was superior to methotrexate based on ACR20 response. In the RA-BEGIN trial, 584 patients who had limited or no prior treatment with methotrexate and who had never received other conventional or biologic disease-modifying antirheumatic drugs (DMARDs) were randomized to methotrexate once weekly (n=210), baricitinib 4 mg once daily (n=159) or baricitinib daily in combination with methotrexate weekly (n=215) for up to 52 weeks. The weekly methotrexate dose was increased from 10 mg to 20 mg over 8 weeks. Improvements compared to methotrexate were seen for baricitinib alone or in combination with methotrexate as early as week 1 for all components of the ACR response (swollen and tender joint counts, pain, patient and physician global assessment of disease activity and physical function). These improvements were maintained at weeks 24 and 52. Baricitinib plus methotrexate also demonstrated significant inhibition of progressive radiographic joint damage versus methotrexate alone in RA-BEGIN, the third phase 3 study of baricitinib in RA to show this finding. The incidence of treatment-emergent adverse events and serious adverse events, including serious infections, was similar across treatment groups through week 52. No cases of tuberculosis or spontaneous gastrointestinal perforation were reported during the study. The most common adverse events observed were consistent with previous studies of baricitinib in RA. Compared to methotrexate, baricitinib monotherapy was associated with lower rates of liver abnormalities, lymphopenia and adverse events leading to interruption, while the combination of baricitinib plus methotrexate was associated with increases in non-serious infections and adverse events leading to permanent discontinuation. Lilly and Incyte announced top-line results in December 2014 for the first phase 3 trial of baricitinib, RA-BEACON, in February 2015 for the second, RA-BUILD, in September 2015 for the third, RA-BEGIN and in October 2015 for the fourth, RA-BEAM. The companies will also share detailed results from the RA-BEAM study at ACR this year and plan to submit additional detailed data from all four studies for presentation in scientific meetings and publication in peer-reviewed journals in 2016.

Is general: Yes