Presentations from the recently concluded American Academy of Dermatology (AAD) Annual Meeting that was held on 17–21 March 2023, in New Orleans, US, provided valuable information on two drugs for plaque psoriasis (PsO). While one readout was for AbbVie’s Skyrizi (risankizumab), a marketed interleukin-23 (IL-23) inhibitor, the other update was for Takeda’s Phase II pipeline candidate, TAK-279, a tyrosine kinase 2 (TYK2) inhibitor.

AbbVie presented late-breaking data from an open-label, single-arm Phase IIIb study that evaluated the efficacy and safety of Skyrizi in patients with moderate-to-severe plaque PsO who had previously experienced a suboptimal response to treatment with IL-17 inhibitors—Novartis’s Cosentyx (secukinumab) or Lilly’s Taltz (ixekizumab). At week 52, 63% of these patients achieved clear or almost clear skin clearance as measured by the static Physician’s Global Assessment (sPGA 0/1). In previously seen data, at week 16, full skin clearance (sPGA 0) was observed in 19.8% of patients.

This isn’t the first time Skyrizi has exhibited promising results in complete skin clearance. In 2020, AbbVie demonstrated Skyrizi’s statistical significance over Cosentyx in the Phase III head-to-head IMMerge trial (NCT03478787). Although IL-17 therapies have been commercially available in the PsO market longer than IL-23 therapies such as Skyrizi, the latter set of therapies has been able to gain traction among patients and physicians alike. One primary reason for this uptake is the fact that IL-23 inhibitors are associated with less frequent dosing compared to IL-17 inhibitors because, mechanistically, IL-23 inhibitors target upstream cytokines compared to those targeted by IL-17 inhibitors (Yang, Oak and Elewski, 2021). Although there is a risk that head-to-head trials comparing competing therapies can play out negatively for the sponsor company, this strategy has reaped results for AbbVie and will serve as key data for messaging Skyrizi to be a formidable player in the crowded PsO biologics space. According to GlobalData’s Sales and Forecast Consensus database, Skyrizi is anticipated to garner global sales of $9.5bn in 2029 in PsO.

Offering a different level of excitement is Takeda’s pipeline candidate, TAK-279. The agent was compared against a placebo in a Phase IIb trial (NCT04999839) in 259 patients with moderate-to-severe plaque PsO who were randomized to receive one of four doses of TAK-279 (2mg, 5mg, 15mg, or 30mg) or a placebo for 12 weeks. 44% of patients in the 5mg cohort, 68% of patients in the 15mg cohort, and 67% of patients in the 30mg cohort achieved a score of 75 on the Psoriasis Area and Severity Index (PASI) measure. Positive trends were also observed in patients achieving PASI 90 versus placebo and the even more stringent endpoint, PASI 100 versus placebo. TYK2 is part of the Janus kinase (JAK) family of kinases, which also includes other kinases such as JAK1, JAK2, and JAK3. JAK inhibitors have been plagued with safety concerns, including infections and haematologic abnormalities, and carry a boxed warning on their US labels. However, TYK2 inhibition potentially impacts a narrower set of inflammatory cytokine pathways compared to other JAK inhibitors, and as such, it is anticipated that the former’s selective inhibition should avoid the toxicities that are associated with JAK inhibitors (Yang, Oak and Elewski, 2021).

Overall, these results reinforce Skyrizi’s stance as a leading biologic in the PsO space and highlight the promise for TAK-279, with the former expected to pull ahead of its competitors and the latter set to advance to Phase III, following Takeda’s announcement on 18 March 2023, of its plans to move to the higher clinical stage in FY2023, based on the positive Phase IIb results.