The FDA approved the first-in-class oral tyrosine kinase 2 (TYK2) inhibitor deucravacitinib (Sotyktu) for moderate-to-severe plaque psoriasis, Bristol Myers Squibb .
The indication limits use to adults who are candidates for systemic therapy or phototherapy. Deucravacitinib is not recommended for use with other immunosuppressant drugs.
"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 clinical program," said April Armstrong, MD, of the University of Southern California in Los Angeles, in a company statement. "People living with moderate-to-severe plaque psoriasis face significant burdens, and Sotyktu is a welcome first-line systemic treatment option."
Support for the approval came primarily from the phase III POETYK PSO-1 and PSO-2 clinical trials, which compared deucravacitinib with placebo and apremilast (Otezla). About 55%-60% of patients in both trials met the primary endpoint of at least 75% improvement in the Psoriasis Area and Severity Index (PASI75) at 16 weeks. More than half the patients met the coprimary endpoint of a Physician Global Assessment (PGA) score of 0/1 (clear/almost clear). Patients randomized to apremilast or placebo had 16-week PASI75 rates of 35.1% and 12.7%, respectively, and PGA 0/1 rates of 32.1% and 7.2%.
Adverse events (AEs) that occurred more often with deucravacitinib than with placebo consisted of upper respiratory infection, increased creatine phosphokinase, herpes simplex, mouth ulcers, folliculitis, and acne. AEs leading to discontinuation occurred in 2.4% of patients treated with deucravacitinib, 3.8% of placebo-treated patients, and 5.2% of patients randomized to apremilast.
TYK2 is a member of the Janus kinase (JAK) family. Deucravacitinib binds to the regulatory domain of TYK2 to stabilize an inhibitory interaction between regulatory and catalytic domains of the enzyme. The company announcement stated that "it is not know whether tyrosine kinase 2 inhibition may be associated with the observed or potential adverse reactions of Janus kinase inhibition."