Bimekizumab at the 2017 ACR Annual Meeting in San Diego

Bimekizumab (alternative names: CDP-4940 and UCB-4940) is a monoclonal antibody that targets IL-17A and IL-17F. Bimekizumab is developed by UCB. Adis insight mentions a phase 3 study for psoriatic arthritis [1]. In 2018 the phase 3 study (BE READY) for plaque psoriasis has been initiated in the USA (NCT03410992): another phase 3 study (BE SURE / NCT03412747) is under plan.

Bimekizumab has been launched with two studies at the 2017 ACR Annual Meeting in San Diego.

A. Maroof and colleagues presented [2]: “Bimekizumab Dual Inhibition of IL-17A and IL-17F Provides Evidence of IL-17F Contribution to Chronic Inflammation in Disease-Relevant Cells”. The authors concluded: “Dual neutralization of IL-17A and IL-17F provides evidence for the contribution of IL-17F to inflammation in joints and skin beyond IL-17A alone. Dual inhibition of IL-17A and IL-17F by bimekizumab may provide an effective treatment for immune-mediated inflammatory diseases such as PsA [psoriatic arthritis].” Nice to know, but …

M. Shah and colleagues elucidated us on [3]: “Bimekizumab Blocks T Cell-Mediated Osteogenic Differentiation of Periosteal Stem Cells: Coupling Pathological Bone Formation to IL-17A and IL-17F Signaling”. The authors concluded: “These data show that both IL-17A and IL-17F enhance in vitro osteogenic differentiation and bone formation […], hence inhibition of both IL-17A and IL-17F with bimekizumab offers an attractive therapeutic strategy to prevent this debilitating feature of SpA [spondyloarthritis].” Also nice to know, but …

Secukinumab (Cosentyx, a human IgG1κ MAB that binds to the protein interleukin IL-17A), brodalumab (Siliq in the US, Kyntheum in Europe, a human MAB that binds to the IL-17-receptor), and ixekizumab (Taltz, a humanized MAB binding to IL-17) are already out on the market. I’m not sure, what UCB is doing. I remember UCB attending the industry exhibition ofan Annual Meetings of ACR or EULAR with an empty information stall, as certolizumab hasn’t been approved in time. Is UCB slowing down, because the market already has been split up? The two studies are perfectly O.K., but not coming up with a phase 1 or 2 study at the 2017 ACR Annual Meeting must be called lack of commitment.

Links and References:

[1] http://adisinsight.springer.com/drugs/800037676

[2] Maroof A, Okoye R, Smallie T, Baeten D, Archer S, Simpson C, Griffiths M, Shaw S. Bimekizumab Dual Inhibition of IL-17A and IL-17F Provides Evidence of IL-17F Contribution to Chronic Inflammation in Disease-Relevant Cells [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/bimekizumab-dual-inhibition-of-il-17a-and-il-17f-provides-evidence-of-il-17f-contribution-to-chronic-inflammation-in-disease-relevant-cells/. Accessed March 8, 2018.

[3] Shah M, Maroof A, Al-Hosni R, Gikas P, Gozzard N, Shaw S, Roberts S. Bimekizumab Blocks T Cell-Mediated Osteogenic Differentiation of Periosteal Stem Cells: Coupling Pathological Bone Formation to IL-17A and IL-17F Signaling [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/bimekizumab-blocks-t-cell-mediated-osteogenic-differentiation-of-periosteal-stem-cells-coupling-pathological-bone-formation-to-il-17a-and-il-17f-signaling/. Accessed March 8, 2018.

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ABT-122 at the EULAR 2014 Meeting in Paris

ABT-122 is an anti-TNF/IL-17 Dual Variable Domain immunoglobulin (DVD-Ig™). It had been "demonstrated that dual neutralization of TNF and IL-17 provides greater efficacy than blocking either cytokine alone in mouse collagen induced arthritis".

Allow me to voice my skepticism already at this point. M. Genovese and colleagues have presented a study two years ago, in which secukinumab (an anti-IL-17a MAB) has been studied in patients with rheumatoid arthritis still active despite methotrexate therapy. “Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 at wk16.” This endpoint hadn’t been achieved. I'm not convinced that IL-17-inhibition is working in rheumatoid arthritis, but let's come to the study, which has been presented in  Paris.

[THU0521]

C. Cuff and colleagues presented this study: "DUAL NEUTRALIZATION OF TNF AND IL-17 WITH A DVD-IG PROTEIN IS EFFICACIOUS IN COLLAGEN INDUCED ARTHRITIS". A mouse study! Conclusions: "These data demonstrate that dual blockade of TNF and IL-17 with a DVD-Ig™ molecule is efficacious in a pre-clinical model of arthritis and support the rationale to clinically evaluate the anti-human TNF/IL-17 DVD-Ig protein, ABT-122, in rheumatoid arthritis and other inflammatory disorders."

I would expect a benefit in " other inflammatory disorders" like psoriatic arthritis or anylosing spondylitis. But ... I have my reservations. Blocking two cytokines at the same time has been avoided so far. All combinations look at a biologic DMARD (boDMARD) and a conventional/chemical DMARD (csDMARD) and not two biologics. The fear is high that one induces more side effects. Even if further studies prove, that ABT-122 isn't working in rheumatoid arthritis, it might open Pandora's box to study combinations of two biologic DMARDs.

Links:

Secukinumab at the EULAR 2012 Meeting: http://rheumatologe.blogspot.de/2012/06/secukinumab-anti-il17a-monoclonal.html