FDA Approves Deucravacitinib for Adults With Moderate-to-Severe Plaque Psoriasis

The FDA has approved deucravacitinib (Sotyktu, Bristol Myers Squibb) for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

The approval of the first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor was based on findings from the phase 3 POETYK PSO-1 and POETYK PSO-2 clinical studies. Across both trials, deucravacitinib showed superior efficacy vs placebo and twice-daily apremilast (Otezla) in 1684 patients 18 years of age and up with moderate-to-severe plaque psoriasis. Deucravacitinib’s superior efficacy was observed at 16 and 24 weeks, with responses continuing through 52 weeks vs placebo and apremilast.

“Sotyktu has the potential to become the new standard of care oral treatment for people with moderate-to-severe plaque psoriasis, given its profile in helping patients achieve clearer skin as demonstrated in the POETYK PSO clinical program,” April Armstrong, MD, MPH, clinical investigator in the POETYK PSO-1 trial and associate dean and professor of Dermatology at the University of Southern California, said in a press release. “People living with moderate-to-severe plaque psoriasis face significant burdens, and Sotyktu is a welcome first-line systemic treatment option.”

POETYK PSO-1 and POETYK PSO-2 analyzed the safety and efficacy of 6 mg once daily deucravacitinib vs placebo and apremilast 30 mg twice daily in patients with moderate-to-severe plaque psoriasis. A total of 664 patients were enrolled in POETYK PSO-1 and 1020 patients were enrolled in POETYK PSO-2, both of which were multi-national, multi-center, randomized, double-blind, placebo- and active comparator-controlled 52-week studies.

All participants across both trials had moderate-to-severe plaque psoriasis and were candidates for phototherapy or systemic therapy, with a body surface area involvement of ≥10%, a Psoriasis Area and Severity Index (PASI) score ≥12, and a static Physician’s Global Assessment (sPGA) ≥3. The co-primary endpoints of both studies were the percentage of patients achieving PASI 75 and the percentage of patients who achieved static sPGA score of 0 or 1 at week 16 compared with placebo. Secondary endpoints included the percentage of patients achieving PASI 75, PASI 90, and sPGA 0/1 vs apremilast at weeks 16 and 24.

The investigators found that responses persisted through week 52, with 82% of 228 patients who achieved PASI 75 with deucravacitinib at week 24 able to maintain the response at week 52 in POETYK PSO-1. In POETYK PSO-2, 80% of 148 patients who continued treatment with deucravacitinib maintained the PASI 75 response vs 31% of 150 patients who were withdrawn from treatment with deucravacitinib.

The most common (≥1% and higher than placebo) adverse events (AEs) reported with deucravacitinib across both trials at week 16 were upper respiratory infections (19.2%), blood creatine phosphokinase increase (2.7%), herpes simplex (2.0%), mouth ulcers (1.9%), folliculitis (1.7%) and acne (1.4%). Further, 2.4% of patients administered deucravacitinib, 3.8% of patients on placebo, and 5.2% of patients on apremilast suffered AEs that led to discontinuation of therapy.

At week 16, infections occurred in 29% of patients in the deucravacitinib cohort vs 22% of patients administered placebo. Most of the infections were not serious, were mild to moderate in severity, and did not cause discontinuation of deucravacitinib.

Serious infections were observed in 5 patients in the deucravacitinib group and 2 patients in the placebo cohort. At week 52, the most common serious infections were pneumonia and COVID-19, with malignancies excluding non-melanoma skin cancer observed in 3 patients administered deucravacitinib, according to the study. Deucravacitinib is not recommended for use in combination with other potent immunosuppressants.

“The approval of Sotyktu represents an exciting day for patients suffering from moderate-to-severe plaque psoriasis who are not satisfied with topical and conventional treatments. This is another extraordinary achievement for Bristol Myers Squibb, as we bring forward a new mechanism of action, the first oral treatment approved in nearly 10 years, and the first orally dosed once-daily treatment for moderate-to-severe plaque psoriasis,” said Samit Hirawat, MD, chief medical officer of Bristol Myers Squibb, in a press release. “We believe Sotyktu is a breakthrough in the treatment of patients with this condition, and we’re excited about its potential in other immune-mediated diseases.”

Reference

U.S. Food and Drug Administration Approves Sotyktu™ (deucravacitinib), Oral Treatment for Adults with Moderate-to-Severe Plaque Psoriasis. Bristol Myers Squibb. News release. September 9, 2022. https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-Sotyktu-deucravacitinib-Oral-Treatment-for-Adults-with-Moderate-to-Severe-Plaque-Psoriasis/default.aspx