Novel oral psoriasis drug maintains efficacy over 2 years

The TYK2 inhibitor deucravacitinib demonstrated stable, long-term efficacy results up to week 112. The outcome measures for the newly FDA-approved drug were very similar to those seen after 1 year.

Deucravacitinib is an allosteric inhibitor of TYK2, which binds to a TYK2 regulatory domain that barely interacts with other JAK enzymes. Compared with JAK1 and JAK3, the selectivity to TYK2 is ≥100-fold and versus JAK2 ≥2,000-fold greater [1]. In the POETYK-PSO-1 trial (NCT03624127), participants received either deucravacitinib at a dose of 6 mg once daily (approved dose), placebo from day 1 to week 16, or apremilast as active comparator [1,2]. Thereafter, placebo participants could cross over to the active study drug. At the pivotal primary endpoint (week 16), 58.4% of the participants treated with deucravacitinib achieved Psoriasis Area and Severity Index (PASI)-75 compared with 12.7% of the placebo-treated participants. This rate further rose to 69.3% at week 24 and 65.1% after 1 year. At the same timepoints, the results for the static Physician’s Global Assessment (sPGA) of 0/1 were within a similar range: 53.6%, 58.7%, and 52.7%, respectively.

Prof. Mark Lebwohl (Icahn School of Medicine at Mount Sinai, NY, USA) presented the latest 112-week extension data on deucravacitinib. Included in the analysis were the longer-term outcomes of all participants who received the active drug from day 1 of the trial, with a special focus on the PASI-75 responders at week 16, who entered the open-label extension after week 52 [3].

Of the 332 participants who were initially randomised to deucravacitinib in POETYK-PSO-1, 265 continued in the long-term extension after week 52 and 173 among them had reached PASI-75 before at week 16. Baseline data of these 2 groups varied somewhat with mean values for the age of 46 years and 45.2 years, weight 87.0 kg and 84.7 kg, PASI 21.8 and 22.6, and sPGA 3 in 78.5% and 74.6%.

Independent of missing data imputation, the PASI-75 outcomes for the cohort with all participants on continuous deucravacitinib resulted in a rather horizontal graph. Prof. Lebwohl stressed that imputation according to “as observed“ or “treatment failure rules” did lead to hardly any change in the results, which he saw as characteristic of a very effective treatment. The outcomes with a modified non-responder imputation (mNRI) went from of 80.2% at week 52 to 82.4% at week 112. The maintenance result for PASI-75 responders at week 16 which started at 90.1% in week 52, attained 91.0% at week 112. sPGA 0/1 was achieved by 66.5% of all extension participants at week 112 and by 73.5% of the 16-week responders.

“So, now, we have a once-daily, oral drug with efficacy similar to biologic agents,” Prof. Lebwohl concluded.

1. Burke JR, et al. Sci Transl Med. 2019;11(502):eaaw1736.
2. Wrobleski ST, et al. J Med Chem. 2019;62(20):8973‒8995.
3. Lebwohl M. Deucravacitinib long-term efficacy with continuous treatment in plaque psoriasis: 2-year results from the phase 3 POETYK PSO study program. D3T01.1F, EADV Congress 2022, Milan, Italy, 7–10 September.
4. Armstrong AW, et al. J Am Acad Dermatol. 2022;S0190‒9622(22)02256‒3.

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Posted on 5 November 202229 February 2024