Study points to efficacy and safety of TYK2 inhibitor BMS-986165 in psoriasis
More patients with moderate-to-severe psoriasis who were treated with the tyrosine kinase 2 (TYK2) inhibitor BMS-986165 achieved improvements in their condition compared with placebo recipients, according to a recent phase II study.
In this multicentre (82 sites in eight countries), double-blind trial, 268 adults (mean age 45 years, 73 percent male, mean PASI* score 18) with moderate-to-severe plaque psoriasis for ≥6 months, body mass index of 18–40 kg/m2, and eligible for systemic therapy or phototherapy were randomized to receive oral BMS-986165 at doses of either 3 mg every other day, 3 mg/day, 3 mg twice/day, 6 mg twice/day, or 12 mg/day, or placebo for 12 weeks. This was followed by a 30-day follow-up for safety assessment.
Patients on higher doses of BMS-986165 appeared to derive better improvements in their condition where, compared with placebo (7 percent), ≥75 percent reduction from baseline in PASI score (PASI 75) at week 12 was experienced by 39 percent of patients on 3 mg/day, 69 percent of patients on 3 mg twice/day, 67 percent of patients on 6 mg twice/day, and 75 percent of patients on 12 mg/day (p<0.001 for all vs placebo). [N Engl J Med 2018;doi:10.1056/NEJMoa1806382]
Patients on the 3 mg every other day dose of BMS-986165 did not significantly differ from placebo recipients in terms of PASI 75 at week 12 (9 percent; p=0.49 vs placebo).
PASI 100 (complete clearance of lesions) was achieved by 2, 9, 18, and 25 percent of patients on BMS-986165 doses of 3 mg every other day, 3 mg twice/day, 6 mg twice/day, and 12 mg/day, respectively, with none of the patients who received placebo or 3 mg/day BMS-986165 experiencing complete clearance of lesions.
Adverse event (AE) incidence was more common in patients who received BMS-986165 compared with those who received placebo, occurring in 59, 55, 64, 80, and 77 percent of patients who received BMS-986165 3 mg every other day, 3 mg/day, 3 mg twice/day, 6 mg twice/day, or 12 mg/day, respectively, vs 51 percent of patients who received placebo. The most common AEs were nasopharyngitis, headache, diarrhoea, nausea, and upper respiratory tract infection.
There were five serious AEs, three of which occurred among patients on BMS-986165 (once case each of rotavirus-related gastroenteritis [3 mg every other day], accidental eye injury [3 mg/day], and vestibular dysfunction-related dizziness [3 mg twice/day]). One patient who received BMS-986165 3 mg/day was diagnosed with melanoma.
There were no reports of herpes zoster infection, opportunistic infections, tuberculosis, or cardiovascular events during the 12-week trial period.
Forty-three patients (16 percent) discontinued treatment, with 2–7 percent of patients in each BMS-986165 treatment group compared with 4 percent on placebo discontinuing due to AEs.
“Results of this phase II trial of BMS-986165 indicate a therapeutic benefit of an oral selective TYK2 inhibitor in psoriasis,” said the researchers.
Due to the relatively small number of participants and short study duration, the researchers called for longer-term studies involving larger populations to validate these findings.