Recent head-to-head trials against secukinumab and adalimumab demonstrated superiority for bimekizumab in treating plaque psoriasis.
In more success for bimekizumab in the plaque psoriasis space, the IL-17A/17F inhibitor has demonstrated superiority over secukinumab and adalimumab in two different trials published last week in the New England Journal of Medicine.
Bimekizumab differs from other currently available anti-interleukin drugs by selectively targeting IL-17F and IL-17A, which are both over-expressed in psoriasis.
Secukinumab (Cosentyx, Novartis) is an 17A inhibitor, while adalimumab (Humira, AbbVie, and biosimilars) is a TNF inhibitor. Earlier this year, the 52-week phase 3 BE VIVID trial found that bimekizumab outperformed ustekinumab, an IL-12/IL-23 inhibitor. All studies were funded by bimekizumab sponsor, UCB Pharma.
Bimekizumab vs secukinumab
The phase IIIb BE RADIANT trial involved 743 patients with moderate-to-severe plaque psoriasis and was conducted across 77 sites in 11 countries, including Australia.
Patients were randomised to receive either bimekizumab or secukinumab, with 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI 100) at week 16 the primary endpoint.
Almost 62% of patients in the bimekizumab group achieved PASI 100 at week 16, compared with around 49% of the secukinumab group, a statistically significant difference.
Secondary end points were PASI 100 at 48 weeks (around 67% for bimekizumab and 46% for secukinumab) and PASI 75 at 4 weeks (around 71% for bimekizumab and 47% for secukinumab).
Both had a similar safety profile, with upper respiratory tract infections, oral candidiasis and urinary tract infections the most commonly reported adverse events. Oral candidiasis was higher in the bimekizumab group (19.3%) than the secukinumab group (3%). This has been reported in other trials of bimekizumab –both IL17A and IL17F play a role in host protection against oral candida infections.
“These data suggest that inhibition of both interleukin-17A and interleukin-17F may provide greater clinical benefit for patients with moderate-to-severe plaque psoriasis than inhibition of interleukin 17A alone,” wrote the study’s authors.
Limitations of the study included the limited racial diversity of the patients, and the exclusion criteria – patients who’d had no response to previous treatment with an IL-17 biologic or more than one biologic agent of any other class within 12 weeks were not eligible for inclusion – potentially reducing generalisability to the real-world psoriasis population.
Bimekizumab vs adalimumab
The phase III BE SURE trial randomised 478 patients to receive adalimumab, or one of two different dosing regimens of bimekizumab. The double-blind, multi-centre trial was conducted in nine countries, including Australia. The primary end point was PASI 90 response and an Investigator Global Assessment (IGA) score of 0 or 1 at week 16.
Around 86% of bimekizumab patients achieved PASI 90 at week 16, compared with 47% of the adalimumab group, and around 85% vs 57% for the bimekizumab and adalimumab groups respectively had an IGA score of 1 or 0. Both were statistically significant differences demonstrating non-inferiority and superiority of bimekizumab over adalimumab.
Around 61% of bimekizumab patients achieved PASI 100, a secondary end point, at week 16, similar with that in the BE RADIANT trial, compared with 24% on adalimumab.
Oral candidiasis and diarrhoea were more common along bimekizumab patients than adalimumab.
Limitations of the trial included the relatively short comparator period of 24 weeks: “too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease”.
Longer and larger trials are required, said the authors.
What about psoriatic arthritis?
There’s evidence that, as in psoriasis, IL-17A and IL-17F play a role in PsA. In a review of the clinical evidence for bimekizumab in PsA, a team from Portugal reported in Drug Design, Development & Therapy that phase I and II trials showed “better outcomes” for bimekizumab than placebo or IL-17A inhibition alone, and recently presented results from open-label extensions were “encouraging”. Results from phase III trials are expected soon.
Bimekizumab is not yet approved by any national regulatory authority. However, approval is anticipated later this year. The patent on UCB’s TNF inhibitor certolizumab pegol (Cimzia), which is used for various rheumatic diseases including psoriasis and psoriatic arthritis, expires in 2025.
Bimekizumab versus Secukinumab in Plaque Psoriasis: NEJM 2021 23 April
Bimekizumab versus Adalimumab in Plaque Psoriasis: NEJM 2021, 23 April
