Long-term bimekizumab for AS is safe, effective, BE AGILE data show
Reduction in symptoms, disease activity maintained after 5 years on therapy
Up to five years of treatment with bimekizumab safely leads to sustained reductions in symptoms and disease activity, as well as improvements in physical function and life quality, for people with ankylosing spondylitis (AS).
That’s according to new data from the now-completed Phase 2b BE AGILE clinical trial (NCT02963506) and its open-label extension study (NCT03355573) that were announced by UCB, the company developing bimekizumab. The data also are being presented Nov. 10-15 at the American College of Rheumatology’s ACR Convergence 2023, in San Diego.
“There is a need for additional treatment options for people living with ankylosing spondylitis since many people do not achieve long-term disease control,” Emmanuel Caeymaex, UCB’s executive vice president of immunology solutions and head of U.S., said in a company press release.
“The five-year bimekizumab data in ankylosing spondylitis demonstrated sustained improvements across multiple domains of disease and a safety profile consistent with previous observations,” Caeymaex added.
Sustained improvements seen for up to 1 year in Phase 2 trial
These long-term findings add to positive one-year results from two Phase 3 trials testing bimekizumab in people with axial spondyloarthritis, or axSpA. This group of inflammatory conditions includes AS and nonradiographic axSpA, a condition with similar symptoms to AS, but without visible damage on an X-ray of the spine.
Phase 2 and 3 trial data supported the approval of the therapy, sold under the brand name Bimzelx, for adults with active axSpA in the European Union earlier this year.
In the U.S., bimekizumab currently is approved to treat adults with moderate to severe plaque psoriasis, a skin condition marked by raised, inflamed, and scaly patches of skin that can be painful and itchy.
Administered subcutaneously, or directly under the skin, bimekizumab is designed to block the activity of interleukin-17A, known as IL-17A, and interleukin-17F, called IL-17F. These two inflammatory signaling molecules play major roles in driving AS and other types of inflammatory arthritis.
The Phase 2b BE AGILE study tested four doses of bimekizumab, given once every four weeks, against a placebo in 303 people with AS. After completing the three months of treatment, all participants received the therapy at one of two higher doses for up to one year.
The results showed that the reductions in symptoms and functional limitations observed with bimekizumab relative to a placebo after three months were sustained for up to one year.
Specifically, one-third to nearly two-thirds of participants achieved ASAS40 — at least 40% improvement on the Assessment in SpondyloArthritis International Society — after up to one year of treatment with bimekizumab.
ASAS40 is a measure that indicates a reduction of at least 40% in three or more of four domains: patient global assessment of disease, pain, function, and inflammation.
202 patients complete extension study of long-term outcomes
A total of 255 patients who completed the trial opted to enroll in an open-label extension study in which they continued to receive bimekizumab and be monitored for long-term outcomes. Of these patients, 202 remained in the extension study for up to 256 weeks, or about five years.
Among those who entered the extension study, 59.8% had achieved ASAS40 at the end of BE AGILE. After five years on the therapy, the ASAS40 rate was nearly identical, at 59%.
“This is the first report of ASAS40 five-year data in patients with ankylosing spondylitis to use a conservative non-responder imputation analysis,” said Atul Deodhar, MD, a professor at Oregon Health and Science University. This type of analysis considers that all patients who discontinued a trial did not respond to the therapy.
“Using this method, the data showed that at least half of the patients treated with bimekizumab achieved sustained improvements through five years of treatment,” Deodhar added.
Another measure of disease severity, the Ankylosing Spondylitis Disease Activity Score or ASDAS, showed similar results. At the end of the original Phase 2b trial, 57.3% of patients who entered the extension study had low disease activity, defined as an ASDAS score lower than 2.1. At five years, 66% of the same group had low disease activity, according to ASDAS scores.
Also, the observed mean reductions in the Bath Ankylosing Spondylitis Disease Activity Index — reflecting less severe disease — at the end of BE AGILE were maintained or showed a further drop at five years.
The data showed that at least half of the patients treated with bimekizumab achieved sustained improvements through five years of treatment.
The Bath Ankylosing Spondylitis Functional Index, which measures physical function, and the Ankylosing Spondylitis Quality of Life questionnaire also showed sustained improvements over five years on bimekizumab, according to UCB.
The inflammatory molecules blocked by bimekizumab are normally important for fighting off fungal infections, including those caused by a yeast called Candida. The rate of Candida infections, which were all mild to moderate, dropped from 7.5 per 100 people per year during BE AGILE to 2.6 at the end of the extension study.
Serious safety-related issues were reported at a rate of 5.2 per 100 people per year over the five years of treatment.