The TYK2 inhibitor may have applications beyond psoriasis.

Deucravacitinib (SOTYKTU, Bristol Myers Squibb) is a first-in-class, oral, selective allosteric TYK2 inhibitor, and has been approved in the United States, European Union, and other countries for use in adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Two abstracts published at Maui Derm 2024 indicated that not only did the drug show longer-term sustained safety and efficacy for plaque psoriasis, but also may be useful for the treatment of lupus erythematosus.

Extension Study Shows Sustained Safety, Efficacy

Deucravacitinib was shown to be superior to placebo in the 52-week POETYK PSO-1 and PSO-2 trials in adults with moderate-to-severe plaque psoriasis. Upon conclusion of the trials, patients were offered the opportunity to participate in the PSO-1 and PSO-2 long-term extension study (LTE). Previously reported data suggested that the therapy sustained safety and efficacy through two years with no new safety signals.

Researchers for the LTE randomly assigned patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast twice daily, with safety analyzed in those patients receiving one or more doses of deucravacitinib. According to the results, a total of 1,519 patients received one or more doses of deucravacitinib, and 513 of them received continuous deucravacitinib from day 1 in the PSO-1 and PSO-2 trials who then enrolled in the LTE. Deucravacitinib maintained its safety and efficacy though 3 years, with no new safety signals emerging.

“Since it is important to provide long-term safety for this new class of drugs, these findings provide additional support for deucravacitinib having a consistent safety profile and durable efficacy for up to 3 years of use.”

During the Psoriasis Update 2024 session, panelist and presenter Bruce Strober, MD, PhD, a clinical professor of dermatology at Yale University, noted during his talk the potential for this new class of drug. He noted data from POETYK PSO-1 and POETYK PSO-2, pointing out that almost 2 out of 3 patients taking deucravacitinib achieved Psoriasis Area and Severity Index (PASI) of 75 at weeks 16 and 24, both significant improvements vs. placebo and apremilast.

“TYK2 inhibition holds a lot of potential beyond psoriasis and psoriatic arthritis,” he added.

Deucravacitinib for Lupus Treatment

A second abstract presented during the Late Breaking Clinical Trials session by Subhashis Banerjee, MD, disease area head at Bristol Myers Squibb, showed the results of a subanalysis of the phase 2 PAISLEY trial in which patients with active systemic lupus erythematosus taking 3 mg of deucravacitinib twice daily showed sustained improvement for the primary endpoint of Systemic Lupus Erythematosus Responder Index (SRI) response at 32 weeks and a ≥ 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score from baseline in those with moderate-to-severe skin involvement at baseline.

For the subanalysis, patients who had SLE and a baseline CLASI score of ≥10 who had received either placebo (n=24), deucravacitinib 3 mg twice daily (n=23), deucravacitinib 6 mg twice daily (n=25) or deucravacitinib 12 mg once daily were included in the analysis.

The results suggested sustained response, showing that more patients receiving deucravacitinib saw a sustained score of CLASI-50 for five consecutive office visits between 32 and 48 weeks (placebo, 12.5%; deucravacitinib 3 mg twice daily, 56.5%; 6 mg twice daily, 36.0%; 12 mg once daily, 58.6%). In addition, more patients achieved a CLASI activity score of 70 at week 48 than those taking placebo. Those in the treatment arms achieved CLASI-50 scores more frequently than those in the placebo group.

Sources

Armstrong A, Lebwohl M, Warren R, et al. Deucravacitinib in plaque psoriasis: 3-year safety and efficacy results from the phase 3 POETYK PSO-1 and PSO-2 trials. Abstract 13616. Presented at: Maui Derm, January 22-26, 2024.

Arriens C, Vollenhoven R, Gottlieb A, et al. Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) achievement and sustained response with deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in a phase 2 trial in systemic lupus erythematosus. Abstract 13629. Presented at: Maui Derm, January 22-26, 2024.

Disclosures

The studies covered in this article were sponsored by Bristol Myers Squibb. Dr. Strober reports being a consultant for Bristol Meyers Squibb. Dr. Banerjee is an employee at Bristol Meyers Squibb.