Eli Lilly and Company and Incyte Corporation have 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.
Companies announced that 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.
“Left untreated or uncontrolled, RA can progress and significantly impact long-term health, career and quality of life,” said Roy Fleischmann, M.D., lead study author and clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas. “If it gains FDA approval, baricitinib could be a new choice for us to turn to, especially for patients who cannot take methotrexate.”
Lilly explained that 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.
Furthemore, 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.
“Reaching clinical remission as soon as possible is important to help prevent irreversible joint damage that could lead to disability,” said Terence Rooney, M.D., medical director, rheumatoid arthritis, Lilly Bio-Medicines.
“These positive results for baricitinib add to the growing body of evidence supporting this balanced JAK1 and JAK2 inhibitor as a potential new once-daily oral treatment option for people living with active RA.”
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 explained.
“A significant medical need remains in the RA community as patients respond differently to different treatments,” said Rich Levy, M.D., chief drug development officer of Incyte.
“We are very pleased with the results of the phase 3 RA-BEGIN study, which show superiority of baricitinib over methotrexate, a commonly used treatment for early RA, and demonstrate baricitinib’s promise as a potential new treatment option that offers patients improved disease control.”
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.