Bimekizumab Leads to Rapid Clinical Improvements in Phase 3 Trials
Reduction in symptoms was apparent within week or 2 of starting treatment
A year of treatment with bimekizumab was safe and significantly eased symptoms of ankylosing spondylitis (AS) in participants of two Phase 3 clinical trials, regardless of whether they had been treated previously with inhibitors of the pro-inflammatory molecule TNF.
“Treatment with bimekizumab resulted in rapid and clinically relevant improvements in outcomes, compared with placebo,” Emmanuel Caeymaex, executive vice president of immunology and U.S. solutions at UCB Biopharma, said in a company press release.
UCB, which is developing bimekizumab, announced top-line results from the trial last year. The findings have now been published in the Annals of the Rheumatic Diseases, in the study “Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.”
Bimekizumab works to block inflammatory signaling molecules IL-17A and IL-17F
Bimekizumab is an investigational therapy designed to block the activity of two inflammatory signaling molecules, interleukin (IL)-17A and IL-17F. Data from an earlier Phase 2b study indicated the treatment could help to ease symptoms of AS.
UCB then sponsored a pair of Phase 3 clinical trials to further evaluate the safety and efficacy of bimekizumab. In both studies, participants were randomly assigned to receive 160 mg of bimekizumab or a placebo, given via injection under the skin every four weeks for the first 16 weeks. After week 16, all participants were treated with bimekizumab for the duration of the year-long studies.
The trial BE MOBILE 2 (NCT03928743) enrolled 332 people with AS, while the parallel study BE MOBILE 1 (NCT03928704) included 254 people with non-radiographic axial spondyloarthritis (nr-axSpA) — a condition with similar symptoms to AS, but without obvious signs of damage on imaging of the spine. Both AS and nr-axSpA are forms of axial spondyloarthritis (axSpA), marked by inflammation in the lower spine.
“BE MOBILE 1 and BE MOBILE 2 represent the first phase 3 studies to evaluate the inhibition of IL-17F in addition to IL-17A with bimekizumab across the spectrum of axSpA,” Caeymaex said.
The observed depth of response as well as the consistency of results in nr-axSpA and AS reinforce our confidence in bimekizumab as a potential new treatment option across the full spectrum of the disease.
Trials compare number of patients showing significant improvement by week 16
In both trials, the main goal was to compare the number of patients who showed at least a 40% improvement on the Assessment of SpondyloArthritis International Society (ASAS40) by week 16 of the trial. ASAS40 is a tool that assesses four domains: back pain, physical function, inflammation, and a patient global assessment of disease activity.
Both trials met the main goal, with significantly more patients on bimekizumab than on placebo hitting ASAS40 after 16 weeks: 44.8% vs. 22.5% in the AS trial, and 47.7% vs. 21.4% in the nr-axSpA study. Bimekizumab also outperformed a placebo across standardized measures of disease activity, physical function, life quality, pain, and spinal mobility.
Among AS patients, the results were similar regardless of whether or not they had taken prior anti-TNF medications.
Analyses indicated that the reduction in symptoms was usually apparent within a week or two of starting bimekizumab — notable clinical differences were observed between the bimekizumab and placebo groups after the first dose of the therapy. The response to therapy was similar in those who switched from placebo to active treatment at 16 weeks.
Data also indicated that the effect of bimekizumab did not decrease over time in the year-long studies. In fact, the number of patients hitting ASAS40 continued to increase out to 24 weeks of treatment, hitting just over 50% in both studies.
Bimekizumab treatment leads to marked reductions in inflammatory markers
Treatment with bimekizumab led to a marked reduction in markers of inflammation, including inflammation of the spine on MRI scans and levels of the inflammatory molecule C-reactive protein.
“In these phase 3 trials, dual inhibition of IL-17A and IL-17F with subcutaneous bimekizumab 160 mg every 4 weeks led to significant improvements in ASAS responses, disease activity, physical function, pain, quality of life and spinal mobility compared with placebo,” the researchers concluded.
Caeymaex added: “The observed depth of response as well as the consistency of results in nr-axSpA and AS reinforce our confidence in bimekizumab as a potential new treatment option across the full spectrum of the disease.”
Safety data from the two clinical trials were overall consistent with findings from earlier studies. Fungal infections occurred in roughly 7% of patients on bimekizumab, but none were considered serious. Other common side effects included the common cold, headache, and diarrhea.
The European Medicines Agency is currently reviewing an application from UCB that seeks approval of bimekizumab for axSpA. The application is supported by data from these studies.