Selective inhibition of tyrosine kinase 2 (TYK2) with an oral agent — BMS-986165 — at a dose of ≥3 mg per day is associated with greater clearing of psoriasis compared with placebo over a 12-week period, according to findings published in The New England Journal of Medicine.
Investigators conducted a phase 2, randomized, double-blind trial (ClinicalTrials.gov identifier: NCT02931838) at 82 sites in the United States, Japan, Poland, Canada, Germany, Latvia, Mexico, and Australia.
The investigators sought to evaluate the use of a TYK2 inhibitor in adults with moderate to severe psoriasis, excluding those with a prior lack of response to agents that target cytokine signaling through the same TYK pathway. Patients were randomly assigned to 1 of the following 6 treatments: BMS-986165 3 mg every other day (n=44); BMS-986165 3 mg daily (n=44); BMS-986165 3 mg twice daily (n=45); BMS-986165 6 mg twice daily (n=45); BMS-986165 12 mg daily (n=44); or placebo (n=45). The primary study end point was a ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) score at week 12, with higher scores denoting greater psoriasis severity.
In an intervention group of the trial, a total of 267 patients received ≥1 dose of the study drug. At week 12, the percentages of patients in each group with PASI 75 were as follows: 7% (3 of 45) of patients receiving placebo; 9% (4 of 44) of those receiving BMS-986165 3 mg every other day (P =.49 vs placebo); 39% (17 of 44) of patients receiving BMS-986165 3 mg daily (P <.001 vs placebo); 69% (31 of 45) of those receiving BMS-986165 3 mg twice daily (P <.001 vs placebo); 67% (30 of 45) of patients receiving BMS-986165 6 mg twice daily (P <.001 vs placebo); and 75% (33 of 44) of those receiving BMS-986165 12 mg daily (P <.001 vs placebo).
Overall, 3 serious adverse events were reported among patients who received the active drug, as well as 1 case of malignant melanoma revealed 96 days following the initiation of therapy.
The investigators concluded that selective inhibition of TYK2 with the orally administered agent BMS-986165 at doses ≥3 mg daily resulted in greater clearing of psoriasis than placebo over 12 weeks. Larger and lengthier studies of the agent are warranted to establish its safety and durability of effect in patients with psoriasis.
Papp K, Gordon K, Thaçi D, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379:1313-1321.