Clinical Focus Department Img 20
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The therapeutic pipeline in psoriasis has been active. Four agents are in late-stage development and could be available for patient use in the relatively near future. Here’s a closer look.

Deucravacitinib. Deucravacitinib is a first-in-class, oral, selective tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action that inhibits the IL-12, IL-23, and Type 1 IFN pathway.

Two Phase 3 trials, POETYK PSO-1 and POETYK PSO-2, evaluated deucravacitinib given as 6mg once daily and met both co-primary endpoints versus placebo, with significantly more patients achieving Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (PGA) score of clear or almost clear (sPGA 0/1) after 16 weeks of treatment with deucravacitinib. Deucravacitinib was more effective than apremilast across multiple endpoints, including PASI 75 and durability and maintenance of response.1

In both Phase 3 trials, deucraviticinib was well-tolerated. The most common adverse events (AEs) (≥5 percent) with deucravacitinib treatment at week 16 were nasopharyngitis and upper respiratory tract infection with low rates of headache, diarrhea, and nausea. At week 16, 2.4 percent of patients on deucravacitinib, 3.8 percent of patients on placebo, and 5.2 percent of patients on apremilast experienced AEs leading to discontinuation. No new safety signals were observed during weeks 16 to 52.

Tapinarof cream. Tapinarof is a first-in-class small-molecule topical therapeutic aryl hydrocarbon receptor (AhR)–modulating agent in clinical development for the treatment of psoriasis and atopic dermatitis. It is naturally derived by bacterial symbionts of entomopathogenic nematodes. The efficacy of tapinarof in psoriasis is attributed to its specific binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of proinflammatory cytokines, including interleukin 17.2

PSOARING 1 and PSOARING 2 are identical Phase 3 randomized, double-blind, vehicle-controlled parallel studies in which 1,025 patients received either tapinarof cream 1% or vehicle once daily for 12 weeks. Following the 12-week studies, patients were given the option to participate in an ongoing 52-week safety study, PSOARING 3.

In PSOARING 1 and PSOARING 2, 35.4 percent and 40.2 percent, respectively, of patients who received tapinarof 1% achieved a PGA score of 0 or 1 at week 12 compared with six percent and 6.3 percent of patients who were treated with vehicle. The most common AEs reported during the studies were nasopharyngitis, contact dermatitis and folliculitis, which were observed primarily at the application site.

Roflumilast cream. Roflumilast cream is a once-daily topical formulation of roflumilast, a highly potent and selective phosphodiesterase type 4 inhibitor (PDE4).

Roflumilast cream 0.3% once daily achieved an IGA score of clear or almost clear and at least a 2-grade improvement from baseline at week 8 in 42.4 percent and 37.5 percent when compared to 6.1 percent in (P<0.0001), and 6.9 percent (P<0.0001) in DERMIS-1 and DERMIS-2, respectively. DERMIS-1 and DERMIS-2 were identical Phase 3 randomized, parallel, double-blind, vehicle-controlled, multi-national, multi-center studies in which roflumilast 0.3% cream or matching vehicle cream were applied once daily for eight weeks to subjects aged two and older with mild, moderate, or severe chronic plaque psoriasis involving between two and 20 percent body surface area.

Bimekizumab. Bimekizumab is an investigational humanized monoclonal immunoglobulin (Ig)G1 antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which are two key cytokines driving the psoriasis inflammatory processes. If approved, bimekizumab will be the fourth biologic available within the class of IL-17 inhibitors.

Bimekizumab has been studied in multiple Phase 3 studies (BE READY, BE SURE, BE VIVID, BE RADIANT) of adult moderate to severe chronic plaque psoriasis patients.

In the BE SURE 56-week trial and 52- week BE VIVID trial, bimekizumab-treated patients demonstrated superior skin clearance at week 16 versus patients treated with adalimumab, ustekinumab and placebo as measured by PASI 90 and IGA response of clear (0) or almost clear (1, 2).3

BE RADIANT is the first Phase 3 study to compare the efficacy and safety of dual IL-17A and IL-17F inhibition versus IL-17A inhibition alone.4 The study met its primary endpoint, with significantly more patients treated with bimekizumab achieving complete skin clearance, as measured by a 100 percent improvement from baseline in the PASI 100 at Week 16, compared to those treated with secukinumab (61.7 percent versus 48.9 percent, respectively (p<0.001).

The most common treatment-emergent adverse events (TEAEs) with bimekizumab were upper respiratory tract infections (38.9 percent), oral candidiasis (19.3 percent), and urinary tract infection (6.7 percent). Oral candidiasis cases were predominantly mild or moderate and none led to discontinuation. Over 48 weeks, the incidence of serious TEAEs was 5.9 percent with bimekizumab and 5.7 percent with secukinumab.

In a press release, UCB announced the FDA has set the Prescription Drug User Fee Act (PDUFA) date for UCB’s Biologics License Application (BLA) for bimekizumab for the treatment of adults with moderate to severe plaque psoriasis on October 15, 2021.

1. Armstrong A. Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, compared with placebo and apremilast in moderate-to-severe plaque psoriasis: results from the phase 3 POETYK PSO-1 POETYK PSO-2 studies. Presented at: American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25,2020; virtual.

2. Bissonnette R, et al. Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent. J Am Acad Dermatol. 2021 Apr;84(4):1059-1067.

3. Reich K, et al. Bimekizumab versus ustekinumab for the treatment of moderate-to-severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo-controlled phase 3 trial. Lancet. 2021 Feb 6;397(10273):487-498.

4. Warren RB, et al. Bimekizumab versus Adalimumab in Plaque Psoriasis. N Engl J Med. 2021 Apr 23. Epub ahead of print.

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