Bimekizumab for the treatment of moderate‐to‐severe plaque psoriasis: efficacy, safety, pharmacokinetics, pharmacodynamics and transcriptomics from a phase IIa, randomized, double‐blind multicentre study*

Abstract

Summary Background Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)‐17A and IL‐17F, which is currently under investigation for treatment of moderate‐to‐severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL‐17 inhibitors for psoriasis. Objectives To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies. Methods Forty‐nine patients with moderate‐to‐severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28. Results At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte‐related gene products such as CXCL1 (C‐X‐C motif chemokine ligand 1), IL‐8 (encoded by the CXCL8 gene), CCL20 (C‐C motif chemokine 20), IL‐36γ and IL‐17C were profoundly normalized to levels associated with nonlesional skin. Conclusions Here, inhibition of IL‐17F in addition to IL‐17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials.

Bimekizumab for the Treatment of Psoriasis: A Review of the Current Knowledge

“… 17 Similarly, IGA 0/1 was reached by 81.3% of the BKZ+ PBO and 64.7% of the BKZ groups at week 16, and by week 28, the first displayed a stable response, while the latter underwent a dramatic decrease to 18.8%. 17 Concerning safety, TEAEs were reported in 28 (88%) and 15 (88%) of patients in the BKZ + PBO and BKZ group, respectively, leading to treatment discontinuation only in 2 (12%) patients receiving bimekizumab at week 16. 17 Most commonly reported TEAEs were upper respiratory tract infections (18%) and nasopharyngitis (12%) in all the study population.…”

“… 17 As regards efficacy, PASI 90 was achieved by 79.6% of all patients by week 16 (84.4% of the combination group and 70.6% of the BKZ one); anyway, such response was maintained at week 28 only in patients receiving an additional dose of bimekizumab as compared to placebo (64.7% vs 31.3%, respectively). 17 Similarly, IGA 0/1 was reached by 81.3% of the BKZ+ PBO and 64.7% of the BKZ groups at week 16, and by week 28, the first displayed a stable response, while the latter underwent a dramatic decrease to 18.8%. 17 Concerning safety, TEAEs were reported in 28 (88%) and 15 (88%) of patients in the BKZ + PBO and BKZ group, respectively, leading to treatment discontinuation only in 2 (12%) patients receiving bimekizumab at week 16.…”

“…Data regarding the effectiveness and safety of bimekizumab for the treatment of psoriasis are reported in Table 1 . 8 , 9 , 12 , 13 , 17–21 …”

“…The maintenance dose interval of bimekizumab was evaluated in a multicentric, prospective, randomized, phase IIa study ran by Oliver et al (NCT03025542). 17 A total of 49 patients were 2:1 randomized to receive subcutaneous bimekizumab 320 mg at week 0, 4 and placebo at week 16 [the bimekizumab plus placebo (BKZ+PBO) group (n = 32)] or bimekizumab 320 mg at week 0, 4 and 16 (the BKZ group, n = 17). 17 As regards efficacy, PASI 90 was achieved by 79.6% of all patients by week 16 (84.4% of the combination group and 70.6% of the BKZ one); anyway, such response was maintained at week 28 only in patients receiving an additional dose of bimekizumab as compared to placebo (64.7% vs 31.3%, respectively).…”

“… 17 A total of 49 patients were 2:1 randomized to receive subcutaneous bimekizumab 320 mg at week 0, 4 and placebo at week 16 [the bimekizumab plus placebo (BKZ+PBO) group (n = 32)] or bimekizumab 320 mg at week 0, 4 and 16 (the BKZ group, n = 17). 17 As regards efficacy, PASI 90 was achieved by 79.6% of all patients by week 16 (84.4% of the combination group and 70.6% of the BKZ one); anyway, such response was maintained at week 28 only in patients receiving an additional dose of bimekizumab as compared to placebo (64.7% vs 31.3%, respectively). 17 Similarly, IGA 0/1 was reached by 81.3% of the BKZ+ PBO and 64.7% of the BKZ groups at week 16, and by week 28, the first displayed a stable response, while the latter underwent a dramatic decrease to 18.8%.…”