The FDA has approved first-in-class oral tyrosine kinase 2 (TYK2) inhibitor deucravacitinib (Sotyktu) for moderate to severe plaque psoriasis, Bristol Myers Squibb announced.
The indication limits use to adult candidates for systemic therapy or phototherapy. Deucravacitinib is not recommended for use with other immunosuppressive drugs.
“Sotyktu has the potential to become the new gold standard oral treatment for people with moderate to severe plaque psoriasis, given its profile for helping patients achieve clearer skin, as demonstrated in the POETYK clinical program PSO,” April Armstrong said. , MD, of the University of Southern California at Los Angeles, in a company statement. “People with moderate to severe plaque psoriasis face significant burdens, and Sotyktu is a welcome first-line systemic treatment option.”
Approval support came primarily from the Phase III POETYK PSO-1 and PSO-2 clinical trials, which compared deucravacitinib to placebo and apremilast (Otezla). Approximately 55% to 60% of patients in both trials achieved the primary endpoint of at least 75% improvement in the Psoriasis Area and Severity Index (PASI75) at 16 weeks. More than half of patients met the co-primary endpoint of a Physician’s Global Assessment (PGA) score of 0/1 (clear/almost clear). Patients randomized to receive apremilast or placebo had PASI75 rates at 16 weeks of 35.1% and 12.7%, respectively, and PGA 0/1 rates of 32.1% and 7.2%.
Adverse events (AEs) occurring more often with deucravacitinib than with placebo included upper respiratory tract infection, increased creatine phosphokinase, herpes simplex, mouth ulcers, folliculitis, and acne. Adverse events leading to treatment discontinuation occurred in 2.4% of deucravacitinib-treated patients, 3.8% of placebo-treated patients, and 5.2% of patients randomized to apremilast.
TYK2 is part of the Janus kinase (JAK) family. Deucravacitinib binds to the regulatory domain of TYK2 to stabilize an inhibitory interaction between the regulatory and catalytic domains of the enzyme. The company’s announcement stated that “it is unknown whether tyrosine kinase 2 inhibition may be associated with observed or potential adverse effects of Janus kinase inhibition.”