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Positive Results for Bimekizumab for Axial Spondyloarthritis in Two Phase 3 Trials

Manchester — Bimekizumab, a humanised anti-IL17A and anti-IL-17F monoclonal antibody, significantly improved key symptoms and signs of disease, physical function and quality of life compared with placebo, in axial spondyloarthritis (axSpA) for both TNFi-naïve and TNF-experienced patients.

Data on both disease activity and function, as well as quality of life, from the two phase 3 clinical trials in both adults with active non-radiographic axial spondyloarthritis (nr-axSpA; BE MOBILE 1) and with active ankylosing spondylitis (AS; BE MOBILE 2) were presented by Dr Karl Gaffney, consultant rheumatologist at Norfolk and Norwich University Hospital, Norwich, and lead clinical trial investigator for BE MOBILE 1 and 2, at this year's British Society for Rheumatology (BSR) conference.

"Axial spondyloarthritis has limited treatment options, so this is a welcome addition to the armamentarium with only three classes of advanced therapies available which fall under the umbrella of TNF, IL-17 and JAK inhibitors," said Professor Gaffney . 

"This drug potentially offers a new approach to the treatment of axSpA by virtue of the addition of IL-17F inhibition which theoretically may result in enhanced efficacy," he said, adding that, "However, in the absence of head-to-head trials it's impossible to say this with confidence." 

The results are encouraging for this group of patients who are, on average, diagnosed 8.5 years after presentation, and as such, the delay can have serious consequences for patient outcomes. he added.

"Many patients don't respond to TNF inhibitors, or lose response over time, so bimekizumab offers an additional opportunity to control disease in this challenging group of patients," Prof Gaffney said.

Disease Activity and Function, and Quality of Life Data Reported

The two phase 3 studies (BE MOBILE 1 and 2) had similar designs with patients randomised (1:1 in BE MOBILE 1 and 2:1 in BE MOBILE 2) to receive bimekizumab 160 mg every 4 weeks, or placebo until week 16 (double-blind period), and then a switch to bimekizumab 160 mg every 4 weeks through to week 52 (maintenance period), with ongoing open label follow up.  

"These patients had severe long-standing active disease of at least 9 years, with high disease activity scores and objective evidence of inflammation including laboratory markers and imaging," highlighted Prof Gaffney. 

The primary endpoint was the proportion of patients achieving ASAS40 (Assessment of Spondyloarthritis International Society 40) at week 16 in both studies. 

At the BSR, the ASAS40 and BASDAI50 (Bath ankylosing spondylitis disease activity index 50) rates, as well as the mean change from baseline in BASDAI and BASFI (Bath Ankylosing Spondylitis Functional Index) scores up to 6 months were reported. The Ankylosing Spondylitis Quality of Life (ASQoL) score was also presented. 

Magnitude of Response Maintained to Week 24

The data showed improvements in disease activity, physical function, and quality of life that were consistent across the axSpA disease spectrum, both in TNFi-naïve patients and those who had shown an inadequate response (IR) to TNFi (TNFi-IR). 

A total of 94.5% of randomised patients with nr-axSpA (240/254) and 94.3% of randomised patients with AS (313/332) completed the trial up to week 24. 

The primary endpoints were met in both studies. At week 16, in nr-axSpA patients, the ASAS40 response was achieved in 47.7% versus 21.4 (P<0.001) in patients on bimekizumab versus placebo overall. In TNFi-naïve patients, ASAS40 was achieved in 46.6% versus 22.9% (P<0.001), respectively, and in TNFi-IR, ASAS40 was achieved in 60% versus 11.8%, respectively. 

Again, at week 16, in AS patients, the ASAS40 response was achieved in 44.8% versus 22.5% in patients on bimekizumab versus placebo overall. In TNFi-naïve patients, ASAS40 was achieved in 45.7% versus 23.4%, respectively, and in TNFi-IR, ASAS40 was achieved in 40.5% versus 17.6%, respectively.

A greater improvement in symptom severity (as assessed with BASDAI) and physical function (as assessed with BASFI) were seen at week 16 for bimekizumab versus placebo.

"Here at BSR, I presented the week 24 data, which also demonstrated that patients who switched from placebo to active drug at week 16 achieved the same magnitude of response by 24 weeks [52.4% vs 46.8% ASAS40 bimekizumab versus placebo-bimekizumab]," reported Prof Gaffney in an interview with Medscape News UK

"The magnitude of the response among the TNF inhibitor-experienced patients was numerically higher than the TNFi-naïve. "However, numbers are small and this requires further investigation," he added.

Regarding quality of life scores, a significantly greater improvement was also seen in patients on bimekizumab compared with those on placebo in the mean change from baseline to week 16 for ASQoL in both studies (P<0.001). In nr-axSpA, the mean change was -5.2 for patients on compared with -2.5 for placebo patients, and for patients with AS the meab=n change was -5 for patients on bimekizumab versus -3.2 in placebo patients. 

The proportion of patients showing a reduction four points or greater in the ASQoL score – in patients with a baseline score ≥4 – was 58.6% versus 33.3% in nr-axSpA patients on bimekizumab and placebo, respectively. In AS patients, the proportions were 57.5% and 45%, respectively. 

Safety results showed that the treatment was well tolerated and there were no unexpected safety signals over 24 weeks. 

Dr Dale Webb, FRSPH, and chief executive officer of the National Axial Spondyloarhtritis Society (NASS) commented on the results. "We welcome the possibility of an additional option for people with axial SpA, as we know not every patient has a good response to the existing biologic treatments," he told Medscape News UK. "We wait with optimism the next stage of the process including the technology appraisal conducted by the National Institute for Health and Care Excellence." The NICE appraisal is currently in progress. 

In 2021, bimekizumab was approved in the European Union (EU)/European Economic Area (EEA) and in the UK for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. UCB, the drug developer, will also be presenting data from two Phase 3 studies evaluating the efficacy and safety of bimekizumab in bDMARD-naïve patients with active psoriatic arthritis (PsA; BE OPTIMAL) and in tumour necrosis factor inhibitor-inadequate responder (TNFi-IR) patients with active PsA (BE COMPLETE) at BSR 2023.

Professor Gaffney declares support from NASS, AbbVie,Pfizer,UCB, Novartis, Lilly, Celgene, Celltrion, Janssen, Gilead, Biogen, and Galapagos. Dr Webb has no conflicts of interest to declare other than that UCB fund the Act on Axial SpA programme but have no editorial control over the content of the programme.