tildrakizumab

Tildrakizumab is an active substance administered subcutaneously at a dosage of 100 mg. It is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. The application for marketing authorisation was submitted on 6 March 2017, with a positive opinion issued on 26 July 2018.

In clinical trials, tildrakizumab demonstrated efficacy in achieving a PASI 75 response rate of 63.8% and 62.3%, compared to 5.8% in a comparator arm. Similarly, a PGA 'clear' or 'minimal' with at least 2-grade reduction was observed in 57.9% and 59.1% of patients, versus 7.1% in a comparator arm. Another trial reported PASI 75 response rates of 61.2% and 65.6%, compared to 5.8% and 48.2% in comparator arms. PGA 'clear' or 'minimal' with at least 2-grade reduction was 54.7% and 59.2%, compared to 4.5% in a comparator arm.

Safety findings include a No Observed Adverse Effect Level (NOAEL) of 140 mg/kg in a 3-month repeat dose study and 100 mg/kg in a 9-month repeat dose study. The exposure margin at NOAEL in cynomolgus monkeys was >100-200 times higher than in humans. Tildrakizumab levels in breast milk at PPD28 were 0.252 µg/ml. The fetal/maternal ratio for tildrakizumab serum concentration ranged from approximately 1 at PND 7 to 2.17–4.9 at PND 180.