New and emerging therapies for psoriasis

Lluís Puig, Spain

Wednesday, 11 Oct 2023
14:35 – 14:55 CEST

Emerging therapeutic strategies in the field of psoriasis continue to be oriented toward direct or indirect inhibition of the IL-23/Th17 pathway, currently considered the core of the psoriasis pathogenetic paradigm. Inhibition of both IL-17A and IL-17F with bimekizumab may provide faster response and greater degrees of clearance than inhibition of IL-17A alone and other biologic therapies, according to the results of active comparator clinical trials and the estimates of network meta-analyses. Furthermore, bimekizumab has been recently approved for the treatment of psoriatic arthritis (PsA) and axial spondyloarthritis in the European Union, and clinical development for hidradenitis suppurativa (HS) is ongoing.

The market for injectable drugs in psoriasis is relatively crowded, two IL-17A inhibitors of small molecular size are undergoing development for PsA and HS, with highly promising results: sonelokimab, a nanobody with one IL-17A binding domain, one dual IL-17A/F binding domain and one albumin binding domain, and izokibep, an IL-17 ligand trap comprising two IL-17A-specific Affibody domains and one albumin-binding domain. The small molecular size provides improved tissue penetration, whereas albumin binding improves pharmacokinetics by prolonging the half-lives of these molecules. Spesolimab, an IL-36 receptor inhibitor, has recently been approved for the treatment of flares of generalized pustular psoriasis, and imsidolimab is also being developed in this indication.

The approval of deucravacitinib, an oral allosteric Tyk2 inhibitor, for the treatment of psoriasis, is the best example of the growing interest in oral treatments for psoriasis. Deucravacitinib is currently undergoing development for PsA and other indications. Potential competitors with the same mechanism of action include zasocitinib and VTX958. On the other hand, interest in JAK1 inhibitors for PsA continues growing after the approval of upadacitinib; they include brepocitinib, filgotinib and ivarmacitinib.

Oral drugs that interfere with cytokine receptor signalling are also raising expectations (and the interest of the big pharma industry) in the treatment of psoriasis: DC-806 targets IL-17 signalling and JNJ-2113 is an oral IL-23R antagonist peptide. Orismilast (LEO-32731) is a new PDE4 inhibitor undergoing clinical trials in psoriasis and other potential indications.
Finally, topical treatments for psoriasis include the recently FDA-approved tapinarof and roflumilast, but their prices may become a hindrance in other markets.

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