Bimekizumab gains EC approval for hidradenitis suppurativa

22nd April 2024

Bimekizumab (brand name Bimzelx) has been granted marketing authorisation by the European Commission (EC) for active moderate-to-severe hidradenitis suppurativa (HS), its manufacturer UCB has announced.

Now indicated for adults with an inadequate response to conventional systemic HS therapy, the humanised monoclonal IgG1 antibody is designed to selectively inhibit the two cytokines interleukin 17A (IL-17A) and interleukin 17F (IL-17F).

This approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use in March 2024 and makes bimekizumab the first biologic for moderate-to-severe HS to target IL-17F in addition to IL-17A.

It also marks the fourth marketing authorisation for the drug, adding to the existing indications in moderate-to-severe plaque psoriasis, active psoriatic arthritis and active axial spondyloarthritis.

Professor Christos Zouboulis, director of the departments of dermatology, venereology, allergology and immunology at Städtisches Klinikum Dessau, Brandenburg Medical School, Germany, and president of the European Hidradenitis Suppurativa Foundation, said: ‘The European Commission’s approval of bimekizumab marks a significant milestone for the EU hidradenitis suppurativa community, particularly considering the limited treatment options currently available.

‘As a community, we strive to improve the management of hidradenitis suppurativa. Bimekizumab offers a promising new therapeutic option for moderate to severe disease, supported by Phase 3 evidence that demonstrated clinically meaningful and sustained responses over 48 weeks.’

Indeed, the EC approval was based on results from the BE HEARD I and BE HEARD II studies, which evaluated the efficacy and safety of bimekizumab in the treatment of moderate-to-severe HS.

Clinically meaningful improvements with bimekizumab

The multicentre, randomised, double-blind, placebo-controlled phase 3 trials had a combined enrolment of 1,014 adult patients with a diagnosis of moderate to severe HS.

The primary endpoint in both studies was HiSCR50 at Week 16, with HiSCR75 at Week 16 as a key secondary endpoint. These are defined as at least either a 50 or 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count.

A significantly higher proportion of patients treated with bimekizumab versus placebo achieved a 50% or greater improvement in HS signs and symptoms at Week 16, as measured by HiSCR50.

Bimekizumab treatment also resulted in clinically meaningful improvements in the ranked key secondary endpoint, HiSCR75 versus placebo at Week 16. 

Responses were maintained to Week 48, and the safety profile of bimekizumab was consistent with safety data seen in previous trials with no new observed safety signals.

MHRA approves bimekizumab for psoriatic arthritis and axial spondyloarthritis

31st August 2023

Bimekizumab is now approved for use by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of adults with active psoriatic arthritis (PsA) and active axial spondyloarthritis (axSpA), its manufacturer UCB has announced.

The MHRA approval of bimekizumab (brand name Bimzelx) makes the drug the first approved treatment both both conditions that works as a dual IL-17A and IL-17F inhibitor, both of which have ben implicated in driving the inflammatory processes associated with PsA and axSpA.

Bimekizumab can be used alone or in combination with methotrexate, for the treatment of adults with active PsA who have had an inadequate response or who have been intolerant to one or more disease-modifying anti-rheumatic drugs.

The AxSpA indication spans both non-radiographic axSpA (nr-axSpA) and ankylosing spondylitis (AS), also known as radiographic axSpA (r-axSpA).

For adults with nr-axSpA, bimekizumab can be used where there are objective signs of inflammation, as indicated by elevated C-reactive protein and/or magnetic resonance imaging, or for those who have responded inadequately or are intolerant to non-steroidal anti-inflammatory drugs. It can also be used for the treatment of adults with active r-axSpA who have responded inadequately or are intolerant to conventional therapy.

Claire Brading, managing director UK and Ireland at UCB, said: ‘The approval of Bimzelx in psoriatic arthritis and axial spondyloarthritis is a significant milestone for the rheumatology community in the UK.‘

She added: ‘We are extremely proud to be able to bring a new dual action biological treatment option to a broad range of people living with psoriatic arthritis and axial spondyloarthritis in the UK.‘

Bimekizumab clinical efficacy

The MHRA approval for use in PsA was based on the findings of two randomised, double-blind, placebo-controlled phase 3 trials, BE OPTIMAL and BE COMPLETE. In both studies, bimekizumab met the primary endpoint of a 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 and all ranked secondary endpoints.

Consistent results were seen across both biologic-naive and TNF-inhibitor (TNFi) inadequate responder populations and the clinical responses achieved at Week 16 were sustained up to Week 52 in BE OPTIMAL.

In addition, among biological DMARD-naive and TNFi patients with an inadequate response, 47% and 59% of patients with baseline psoriasis affecting ≥ 3% body surface area receiving bimekizumab achieved a PASI100 at Week 16, respectively compared to only 2% and 5% receiving placebo.

The approval for axSpA was also based on the findings of two phase 3 trials, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Bimekizumab met the primary endpoint of Assessment of SpondyloArthritis international Society ≥40% improvement response at Week 16 compared to placebo and all ranked secondary endpoints.

Indeed, the drug showed improvements compared to placebo in signs, symptoms and disease activity across the spectrum of disease.

Commenting on bimekizumab’s approval, Professor Karl Gaffney, rheumatologist at the Norfolk and Norwich University NHS Foundation Trust, said: ‘Psoriatic arthritis and axial spondyloarthritis are chronic, painful conditions with no cure. The unfortunate reality for many patients is that they will have to cycle through a number of treatments before eventually finding one that works for them.

‘I welcome the possibility of a new, dual-action, biologic treatment option to potentially improve the quality of life of people living with psoriatic arthritis and axial spondyloarthritis.‘

Earlier this year, bimekizumab was found to provide clinical benefit in patients with moderate to severe hidradenitis suppurativa.

Bimekizumab shows promise in hidradenitis suppurativa

13th April 2023

Bimekizumab appears to be an effective treatment for patients with hidradenitis suppurativa, according to the findings of a phase 3 trial.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder affecting intertriginous areas of skin. and affects around 1% of the population. Clinically, patients experience cutaneous inflamed nodules, abscesses and pus-discharging tunnels that develop in axillary, inguinal, gluteal and perianal body sites.

There is often a diagnostic delay and which leads to more severe disease. Bimekizumab is a humanised, monoclonal antibody that selectively inhibits both IL-17A and IL-17F. A phase 2 trial found use of the drug led to clinically meaningful improvement in patients with HS.

In the recent study, data from two phase 3, randomised, placebo-controlled trials in adult patients with moderate to severe HS. Both trials had a 16-week initial and 32-week maintenance treatment period.

Bimekizumab was used at a dose of 320 mg every two weeks and 320 mg every four weeks. The Hidradenitis Suppurativa Clinical Response (HiSCR50) served as the primary outcome measure. This is defined as a 50% decrease in the total abscess and inflammatory nodule count, with no increase in abscess or draining tunnel count.

Bimekizumab and HS outcomes

There were 1,014 patients in the two trials. In both trials at week 16, more patients using bimekizumab achieved the primary outcome compared to placebo. For example, 45.3% vs28.7%, p = 0.030 (BE HEARD 1) and 53.8% vs 32.2%, p = 0.004 ( BE HEARD II). These improvements were seen for both drug regimens. In addition, over 75% percent of patients using bimekizumab achieved HiSCR50 and over 55% a HiSCR75 at week 48.

The company will submit data for global regulatory approval of the drug in patients with moderate to severe HS later in 2023.

Two phase 3 trials find bimekizumab effective in both forms of axial spondyloarthritis

2nd March 2023

Bimekizumab which provides dual inhibition of interleukin 17A and 17F significantly improved symptoms in those with axial spondyloarthritis

Use of bimekizumab in patients with both radiographic and non-radiographic axial spondyloarthritis produced significant and rapid improvements in disease outcomes in two parallel randomised trials by a European research group.

Axial spondyloarthritis (axSpA) represents a chronic inflammatory disease involving the axial skeleton that gives rise to chronic back pain and spinal stiffness but which may also include peripheral and extra-musculoskeletal manifestations. The term includes two forms of the condition, those with either radiographic and non-radiographic disease, with patients in this latter group representing those who are symptomatic but no evidence of definitive damage seen on pelvic radiographs.

It has become recognised that the interleukin-17A (IL-17A) pathway is implicated in the pathogenesis of axial spondyloarthritis although IL-17F has also been shown to induce similar inflammatory changes to IL-17 in joints. In fact, use of bimekizumab, which is a dual IL-17A and IL-17F blocker, is effective in psoriatic arthritis, which can also present with axial involvement in up to 50% of patients.

With data from a phase 2IIb trial in active ankylosing spondylitis, proving that bimekizumab was effective, in the current study, researchers undertook two parallel randomised, double-blind, placebo-controlled phase 3 trials of the drug in patients with both forms, i.e., non-radiographic (nr-disease) and radiographic (r-disease) axial spondyloarthritis. Participants with active nr-disease were randomised 1:1 and 2:1 (r-disease) to bimekizumab 160 mg every 4 weeks and from week 16 through to 52, all patients received bimekizumab 160 mg every 4 weeks. The primary endpoint was based on the Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40), i.e., a 40% improvement is disease severity.

Bimekizumab and disease improvement

At baseline virtually all patients (> 97.6%) had high or very high disease activity. In total, 254 patients with nr-disease and a mean age of 39.4 years (54.3% male) and 332 with r-disease and a mean age 40.1 years (72.2% male) with were included in the analysis.

At week 16, there was a significantly higher proportion of participants achieving an ASAS40 in both trials (nr-disease 47.7% vs 21.4% and r-disease 44.8% vs 22.5%, p<0.001 in both cases). Moreover, improvements became apparent within one to two weeks after starting bimekizumab in both trials.

The most frequent treatment emergent adverse events (i.e. occurring in > 3% of patients) with bimekizumab included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis.

The authors concluded that the use of the dual IL-17A and IL-17F inhibitor bimekizumab gave rise to significant and rapid improvements in patients with both radiographic and non-radiographic axial spondyloarthritis and was well tolerated.

Citation
van de Heijde D et al. Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials. Ann Rheum Dis 2023

EU approves bimekizumab for moderate to severe psoriasis

24th August 2021

Bimekizumab is the first agent that inhibits the two cytokines IL-17A and 1L-17F which are both involved in the development of psoriasis.

Psoriasis is best described as a complex, chronic, multifactorial and inflammatory disease characterised by increased proliferation of keratinocyte cells in the skin giving rise to silvery/white plaques. The disease typically presents on extensor surfaces such as the elbows, knees and lower back and there if often involvement of the scalp. The incidence of psoriasis appears to vary across the world, with a recent study noting a wide variation. For instance, the incidence was 30.3 per 100,000 person years in Taiwan but 321 per 100,000 person years in Italy.

Among those with psoriasis, one study of over 9,000 patients, found that just over half (51.8%) had mild disease, with 35.8% and 12.4% having moderate and severe disease respectively. Patients with mild to moderate disease are normally managed with topical therapies, whereas those with moderate to severe disease are increasing treated with biological agents, in particular, monoclonal antibodies. Although the precise cause of psoriasis remains to be determined, several interleukins appear to be important disease drivers, especially the interleukin-17 (IL-17) pathway which includes six similar agents, IL-17A – IL-17F.

Research suggests that two members of the IL-17 family, IL-17A and IL-17F are implicated in autoimmunity and IL17F appears to regulate pro-inflammatory gene expression and which requires the IL-17A receptor, suggesting that both are involved in the pathology of psoriasis. Bimekizumab is the first monoclonal antibody which selectively inhibits both IL-17A and IL-17F and is therefore a potentially important advancement in the management of patients with moderate to severe psoriasis.

Clinical efficacy
The EU approval of bimekizumab was supported by the results of three phase 3 clinical trials, all undertaken in patients with moderate to severe psoriasis. The first, BE READY, randomised 435 patients (4:1) to bimekizumab 320 mg every 4 weeks or placebo. The co-primary endpoint was a PASI90 (i.e., 90% improvement in disease severity compared to baseline) and the proportion of patients achieving a score of 0 (i.e., clear skin) or 1 (almost clear), based on a 5-point investigator global assessment (IGA) score after 16 weeks of treatment.

The results showed that a staggering 91% of those assigned to bimekizumab achieved a PASI90 compared to only 1% in the placebo group. In the BE VIVID trial, 567 patients were randomised to bimekizumab (at the same dosage as the BE READY trial) or this time, ustekinumab 45 or 90 mg every 12 weeks and which is an active comparator or placebo. Once again at week 16 there was a high response in the bimekizumab group with 85% achieving a PASI90 compared to 50% in the ustekinumab. The third trial, BE SURE, enrolled 478 patients who were randomised to either bimekizumab (same dosage as in the other trials) or adalimumab (another active comparator) at a dose of 40 mg every 2 weeks. At week 16, a PASI90 was achieved 85.3% of those using bimekizumab and 57.2% of those given adalimumab.

The most common adverse effects from bimekizumab are upper respiratory tract infections (14.5%) and patients are advised to seek medical advice if they display symptoms suggestive of an infection.
The EU approval applies to all 27 member states as well as Iceland, Liechtenstein and Norway at a dose of 320 mg administered by subcutaneous injections every 4 weeks for week 16 and every 8 weeks thereafter. The drug is currently under review by the US Food and Drug administration.