SAN FRANCISCO, CA—The investigational agent olokizumab is well-tolerated, with “a safety profile expected for this class of agent” among patients with rheumatoid arthritis (RA) for whom previous anti-tumor necrosis factor (TNF) therapy had failed, according to data from two open-label extension studies presented at the 2015 ACR/ARHP Annual Meeting.
The efficacy and safety of olokizumab, a humanized anti-interleukin-6 monoclonal antibody, were assessed in two 12-week randomized controlled trials in patients with RA. One of the studies (RA0056) included patients from the USA, United Kingdom, and Belgium; the other (RA0083) enrolled patients from Japan, Korea, and Taiwan.
In the studies, patients received placebo, subcutaneous olokizumab 60/120/240mg every 2 weeks or every 4 weeks (240mg every 2 weeks in RA0056 only), or, in RA0056 only, intravenous tocilizumab 8 mg/kg every 2 weeks.
In both studies, olokizumab was associated with significant reductions in disease activity at 12 months vs. placebo.
Mark C. Genovese, MD, of the Division of Rheumatology at the Stanford University Medical Center in Palo Alto, California, and colleagues reported results from two open-label extension (OLE) studies of these trials. Patients who completed the 12-week trials were eligible to participate in the open-label extension studies, RA0057 and RA0089, to assess long-term safety of olokizumab. A secondary objective was to assess long-term efficacy, measured as change from baseline for the extension studies in Disease Activity Score 28 C-reactive protein (DAS28[CRP]).
“Patients with ongoing serious adverse events (SAEs) were excluded,” Dr. Genovese noted.
Participants in the RA0057 study were administered subcutaneous olokizumab 120mg every 2 weeks plus methotrexate (12.5–25.0mg/week to Week 12, after which dose could be reduced). Patients who participated in RA0089 were administered subcutaneous olokizumab 120mg every 2 weeks plus methotrexate (6–16mg/week in Japan, or 7.5–20mg/week in Korea and Taiwan).
“Both open-label extension studies were prematurely terminated owing to a change in sponsorship of the olokizumab program,” they noted. Although the RA0057 study was planned to run for 5 years, data are available to Week 90; for RA0057, which was planned to run to marketing application approval, data are available to Week 89.
“Patients receiving ≥6 months’ treatment in the open-label studies are consideredcompleters,” Dr. Genovese noted.
A total of 198 patients completed the RA0056 study, 190 of whom were enrolled in the RA0057 extension study. Of these, 114 received olokizumab, 40 were administered placebo, and 36 received tocilizumab. A total of 67 (35.3%) patients were “completers,” with a median exposure of 51 weeks.
A total of 105 patients completed the RA0083 trial and 103 were enrolled in RA0089; 79 received olokizumab and 24, placebo. Of these, 79.5% were “completers,” with a median exposure time of 40 weeks.
Treatment-emergent adverse events were reported for 180 Western and 91 Asian patients in the open-label extension studies, Dr. Genovese noted. Safety data were reported for the full safety set, and efficacy outcomes for the full analysis set. Included were patients who received ≥1 dose of olokizumab, with ≥1 efficacy measurement.
Serious treatment-emergent adverse events occurred in 50 (26%) Western participants and 14 (13.6%) Asian participants. In most cases, these serious treatment-emergent adverse events involved infections and infestations or emergence of neoplasms (benign, malignant, or unspecified).
Olokizumab treatment was discontinued due to treatment-emergent adverse events in 33 (17%) and 7 (6.7%) of patients in two studies, respectively.
“Efficacy measures continued to improve in the open-label extension studies, most notably, as expected, in placebo patients switching to olokizumab,” Dr. Genovese reported. “In patients who had received olokizumab or tocilizumab in the randomized controlled trials, reductions in disease activity were either maintained or further improved through Week 48 of the open-label extension [studies].”
“These results support the continued development of olokizumab for the treatment of moderate-to-severe RA,” he concluded.