Kiniksa announces interim results from Phase 1b KPL-716 trial
Kiniksa announced interim repeated-single-dose Phase 1b clinical data for KPL-716, an investigational fully-human monoclonal antibody that targets oncostatin M receptor beta, or OSMRbeta. In this clinical trial, weekly subcutaneous, or SC, doses of KPL-716 resulted in a rapid and sustained reduction in pruritus throughout the 12-week treatment period but also a higher rate of atopic dermatitis flares. The results support Kiniksa's ongoing development of KPL-716 in a Phase 2a clinical trial for prurigo nodularis and an exploratory Phase 2 clinical trial in diseases characterized by chronic pruritus. The repeated-single-dose Phase 1b clinical trial used a weekly 360 mg SC dose in a randomized, double-blind, placebo-controlled design in order to evaluate safety and exploratory disease response markers. The 360 mg SC dose was intended to replicate and extend exposures from the prior single-ascending-dose Phase 1b clinical trial where an early signal of efficacy was observed in reducing pruritus after a single 7.5 mg/kg intravenous dose. In the repeated-single-dose Phase 1b clinical trial, 43 subjects with moderate-to-severe atopic dermatitis were enrolled and randomized 1:1 to KPL-716 or placebo once weekly for 12 weeks. There was a seven-day wash out period of all other therapies before treatment, and topical corticosteroids were not allowed throughout the 12-week treatment period. However, rescue medication was available for atopic dermatitis flares throughout the study. In an interim analysis of the data through the 12-week treatment period, KPL-716 showed a rapid and sustained reduction in Worst-Itch Numeric Rating Scale, or WI-NRS, in subjects with moderate-to-severe atopic dermatitis. Mean change from baseline in weekly-average WI-NRS at Week 1 was -28.1% in KPL-716 recipients compared to -6.8% in placebo recipients. Mean change from baseline in weekly-average WI-NRS at Week 12 was -55.0% in KPL-716 recipients compared to -30.9% in placebo recipients. Overall, 52.6% of KPL-716 recipients demonstrated a four-point reduction in weekly-average WI-NRS at Week 12 compared to 26.3% of placebo recipients. There was no meaningful benefit of repeated-single-doses of KPL-716 on other efficacy endpoints specific to atopic dermatitis, including Eczema Area and Severity Index, or EASI and Scoring Atopic Dermatitis, or SCORAD. There were no serious adverse events. However, there were more atopic dermatitis flares in the KPL-716-treated population versus placebo through the 12-week treatment period; all subjects who experienced a flare were successfully managed with topical corticosteroids. KPL-716 was otherwise well-tolerated by all subjects.