Positive first results in ankylosing spondylitis from the UCB Phase 2b BE AGILE study of bimekizumab show statistical significance in multiple dose groups
- The study achieved the primary endpoint (ASAS40), with up to 47% of patients receiving bimekizumab achieving at least 40% improvement in ankylosing spondylitis (AS) symptoms, versus 13% of patients receiving placebo, at week 12
- The Phase 2b BE AGILE study provides the first clinical efficacy and safety results in AS with bimekizumab, a novel monoclonal antibody that potently and selectively neutralizes both IL-17A and IL-17F, indicating that it may be a promising new therapeutic option for AS patients, a population with high unmet treatment needs
- These data follow the highly encouraging positive clinical results recently reported with bimekizumab in psoriasis
Brussels, Belgium – December 14, 2017 7:00 AM CET – Regulated Information – Inside Information – UCB today announced the Phase 2b BE AGILE study met the primary objective of establishing dose response for bimekizumab, and demonstrated statistically significant efficacy compared to placebo, in adult patients with active ankylosing spondylitis (AS).1
“The results with bimekizumab are remarkable, especially because a stringent ASAS40 primary efficacy threshold was used. Our results showed that AS patients experienced rapid disease improvement, which can truly have a positive impact on patients’ lives,” said Désirée van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center. “By specifically targeting both IL-17A and IL-17F, bimekizumab may halt the inflammation driving the symptoms in a disease like AS.”
“AS is a chronic, painful and progressively debilitating condition that often starts in young adulthood. Patients with AS suffer from morning stiffness, crippling back pain, reduced mobility and functionality. Even with the recent progress in biologic development, up to 40% of patients do not respond well to standard biologic medicines, and there are few therapeutic options available to them. The results of BE AGILE show that bimekizumab has the potential to be a valuable treatment option for AS patients by rapidly and significantly reducing the impact of their disease,” said Emmanuel Caeymaex, Head of Immunology and Executive Vice President at UCB. “We are also developing bimekizumab in further disease states, including psoriasis and psoriatic arthritis. We believe bimekizumab will bring significant value to patients and are committed to rapidly advancing our Phase 3 clinical program.”
BE AGILE investigated the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of bimekizumab compared with placebo in adult patients with active AS. The primary efficacy variable evaluated in the study was the percentage of AS patients who achieved at least 40% improvement in symptoms, such as pain, physical function, and inflammation (ASAS40), at week 12. Bimekizumab achieved this clinical response threshold for a statistically significant greater number of patients than placebo across multiple doses.1 Additionally, bimekizumab was generally well tolerated and no unexpected safety signals were observed.
The most common adverse event observed was the common cold (nasopharyngitis). The BE AGILE study will continue for an additional 36 weeks in a dose-blind manner to evaluate maintenance of efficacy and safety.
These data follow the highly encouraging clinical results recently reported with bimekizumab in psoriasis. In a previous phase 2b study in moderate-to-severe psoriasis, another immune-mediated inflammatory disease, dual neutralization of IL-17A and IL-17F with bimekizumab resulted in up to 60% of patients achieving complete skin clearance (PASI100) at week 12.10 Additionally, results from a third Phase 2b study of bimekizumab in psoriatic arthritis are expected soon.
Bimekizumab is a novel humanized monoclonal IgG1 antibody that potently and selectively neutralizes both IL-17A and IL-17F, two key cytokines driving inflammatory processes. IL-17A and IL-17F have overlapping pro-inflammatory functions and independently cooperate with other inflammatory mediators to drive chronic inflammation and damage across multiple tissues.
Previous early phase clinical studies in psoriasis and psoriatic arthritis have suggested that dual neutralization of both IL-17A and IL-17F with bimekizumab may provide a new targeted approach for the treatment of immune-mediated inflammatory diseases.3,4 Preclinical results in disease-relevant cells have shown that dual neutralization of both IL-17A and IL-17F reduces skin and joint inflammation, as well as pathological bone formation to an extent greater than inhibition of IL-17A or IL-17F alone.4,8,12
UCB is also studying bimekizumab in other disease areas, including psoriasis and psoriatic arthritis. Bimekizumab is not approved by any regulatory authority worldwide.
About Ankylosing Spondylitis (AS)
AS is a chronic, lifelong disease. 10 It is a common type of spondyloarthritis, a family of immune-mediated inflammatory diseases impacting joints, that mainly affects the spine. AS is a painful and progressively debilitating condition, in which ongoing inflammation and disease progression leave patients with reduced mobility and functionality, as well as joint stiffness and crippling pain in affected areas.7
Patients with severe AS may go on to develop spinal fusions (where the bones grow together) over 10 to 15 years, which significantly reduces mobility, and increases disability.5 AS often starts in young adulthood. Family members of those with AS are at higher risk.11,6
There is still significant unmet need in AS. Up to 40% of patients do not respond well to standard of care biologic medicines, and there are few therapeutic options available to those people.7
ABOUT BE AGILE2
BE AGILE is a multi-center, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of bimekizumab compared with placebo in adult patients with active ankylosing spondylitis. The study included a 12-week double-blind treatment period, after which patients continued to a 36-week dose-blind treatment period, with a total treatment duration of 48 weeks.
The study included 303 patients with AS, determined by documented radiologic evidence (X-ray) fulfilling the Modified New York criteria for AS, including symptoms for at least three months and age of onset younger than 45 years. Patients had moderate to severe AS defined as BASDAI score ≥ 4, spinal pain ≥ 4, and either an inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs), intolerance to administration of at least one NSAID, or contraindication to NSAID therapy.
The study included both bio-naïve patients and those who had been previously exposed to anti-TNF treatment.
Patients were randomized into five dose regimens to receive either placebo or bimekizumab every four weeks subcutaneously for 12 weeks. They were then re-randomized to a dose-blind bimekizumab treatment group for 36 weeks. Randomization was balanced across treatment groups. Patients were given the option to enter an extension study at week 48.
The primary efficacy variable evaluated in the Phase 2b BE AGILE study was the percentage of patients who achieved at least 40% disease improvement from baseline at week 12, known as an ASAS40 response.
An ASAS response is defined as an improvement of ≥ 40% and a minimum of two units on a scale of 0 to 10 in at least three of the following domains: patient global assessment of disease activity, pain assessment, function, and inflammation. There should be no worsening at all in the remaining fourth domain.
The secondary efficacy variables in BE AGILE, all assessed at week 12, were change from baseline in ASDAS-CRP, ASAS20 response, ASAS5/6 response, change from baseline in BASDAI, and change from baseline in BASFI.2
- UCB Data on File. December 2017.
- UCB Clinical Study Protocol. Protocol PS0008 Amendment 1. Data on File.
- Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017 May;83(5):991-1001. doi: 10.1111/bcp.13185. Epub 2017 Jan 10.
- Glatt S, Baeten D, Baker T, et al. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomized placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. In Press.
- Barkham N, Kong K O, Tennant A, et al. The unmet need for anti-tumour necrosis factor (anti-TNF) therapy in ankylosing spondylitis. Rheumatology. 2005;44:1277–1281.
- Dean LE, Jones GT, MacDonald AG, et al. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014;53(4):650-7.
- Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011; 377(9783):2127-37.
- 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).
- UCB Data on File. July 2017.
- Spondylitis Association of America. About ankylosing spondylitis. Accessed at https://www.spondylitis.org/Ankylosing-Spondylitis. December 7, 2017.
- Schett et al. Structural damage in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: traditional views, novel insights gained from TNF blockade, and concepts for the future. Arthritis Res Ther. 2011;13:S4.
- Maroof A, Okoye R, Smallie T, et al. Bimekizumab dual inhibition of IL-17A and IL-17F provides evidence of IL-17F contribution to chronic inflammation in disease-relevant cells. Ann Rheum Dis. 201706;76 (suppl.2):213-213.
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