Eli Lilly and Incyte Corporation recently presented comprehensive results from a pivotal Phase 3 clinical trial, RA-BEAM, evaluating baricitinib in the treatment of rheumatoid arthritis (RA). The data were presented during the American College of Rheumatology/Association of Rheumatology Health Professionals’ annual meeting in San Francisco.
The fourth effective Phase 3 clinical trial of baricitinib, RA-BEAM was a 52-week study of an enrolled a group of 1,305 patients with active and moderate-to-severe RA, despite being treated with methotrexate. All patients were randomly assigned to receive treatment with baricitinib 4 mg once daily (n=487), adalimumab 40 mg biweekly (n=330) or placebo once daily (n=488). All RA patients taking part in the trial were under background methotrexate. At week 24, patients under treatment with placebo were crossed over to the group of patients under treatment with baricitinib.
“Rheumatoid arthritis is a lifelong condition, but it can be managed with treatment to help control symptoms, including joint inflammation and fatigue, to slow the progression of the disease and improve a patient’s quality of life,” said Peter Taylor, MA, PhD, FRCP, study author and Norman Collisson chair of Musculoskeletal Sciences in the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford, in a company news release. “These findings suggest that the once-daily oral drug baricitinib, if approved, could provide another treatment option for those with insufficient response to current therapy.”
The clinical results showed a statistical advantage of baricitinib over adalimumab (Humira) following 12 weeks of treatment based on numerous analytical measures of rheumatoid arthritis (RA) disease activity, such as ACR50, ACR70 and ACR20 response rates — combined grades that characterize at least a 70%, 50% and 20% improvement in multiple RA disease activity components. After one week of treatment, improvements in the mean number of tender and swollen joints as well as pain reduction were observed for baricitinib when compared to placebo. Following 52 weeks of treatment, baricitinib was found to significantly improve all seven ACR composite score components in comparison to adalimumab, decreasing the number of swollen and tender joints, reducing pain, and improving patient’s’ physical function. Patient-reported clinical outcomes, such as the severity and duration of morning joint stiffness and the degree of tiredness, measured every day for the first 12 weeks of the study, were all found to be significantly improved with the use of baricitinib when compared to adalimumab.
At week 52, the results showed structural alterations in the patients’ joints, assessed by changes in the modified Total Sharp Score, which were found to be significantly improved for both patients groups treated with baricitinib and adalimumab versus those who were treated with placebo.
The companies had previously revealed that the primary endpoint of the trial, a demonstration of superiority for baricitinib compared to placebo based on ACR20 response rate following 12 weeks of treatment, had been met.
“This is the first phase 3 study showing that a once-daily, oral treatment significantly improved clinical outcomes compared with injectable adalimumab for patients with active RA who were also receiving treatment with methotrexate,” said William Macias, MD, PhD, distinguished medical fellow and global brand development leader, Lilly Bio-Medicines. “Lilly is committed to improving outcomes for patients living with this chronic condition.”
“The positive results of the RA-BEAM trial reinforce the potential of baricitinib to quickly improve RA signs and symptoms, physical function and patient-reported outcomes, while inhibiting joint damage,” said Rich Levy, MD, chief drug development officer, Incyte Corporation. “If approved, this once-daily oral treatment may offer RA patients benefits above those seen with injectable adalimumab.”
The rates of serious adverse events related with the trial were identical for baricitinib and placebo, and were lower for adalimumab. In terms serious infections, the rates were identical across all trial groups. In the adalimumab treatment group there was one reported event of tuberculosis. Four deaths were reported, with one each in the placebo and adalimumab groups, and two in the baricitinib group. Temporary interruptions in treatment due to adverse events occurred with similar frequency across all groups.
Eli Lilly and Company and Incyte Corporation also disclosed data from the RA-BEGIN trial during the meeting, and both companies are planning to submit further data from all four trials for publication in peer-reviewed journals and scientific meetings in 2016.