Nemolizumab in prurigo nodularis up to 100 weeks: OLYMPIA LTE interim analysis

Background: Prurigo nodularis (PN) is a neuroimmune skin disease characterized by the presence of chronic itch (≥6 weeks) and multiple white-pink papules, nodules and/or plaques. Objectives: The OLYMPIA long-term extension (OLYMPIA-LTE) trial evaluates long-term, over 184 weeks, safety and efficacy of nemolizumab in adults with moderate-to-severe PN. Methods: Adults with moderate-to-severe PN, who completed phase 2b (NCT03181503) and phase 3 (OLYMPIA 1&2) lead-in trials, were eligible for the ongoing OLYMPIA-LTE trial. Patients receiving nemolizumab monotherapy (continuous-nemolizumab) during lead-in trials continued their regimen, while those on placebo (nemolizumab-naïve) initiated nemolizumab monotherapy. The primary endpoint was long-term safety. Efficacy assessments included the proportion of patients achieving a ≥4-point improvement from baseline Peak Pruritus Numerical Rating Scale (PP-NRS4), Sleep Disturbance Numerical Rating Scale (SD-NRS4) and Dermatology Life Quality Index (DLQI4) scores, Investigator's Global Assessment (IGA) score 0/1 (clear/almost clear), and 75% healed pruriginous lesions (Prurigo Activity and Severity score item-5b). Observed cases up to week 100, regardless of rescue medication, are presented, without imputation of missing data. Results: At interim analysis data cut-off (21 July 2024), 290/508 (57%) patients completed week 100 (median exposure: 839.5 days). Treatment-emergent adverse events (TEAEs) occurred in 89% of patients (452/508; exposure time-adjusted incidence rate: 197.5/100 patient-years) and were mostly mild/moderate (26%/52%) in severity. TEAEs occurring in ≥5% of patients at any given year were COVID-19 (28%), nasopharyngitis (20%), upper respiratory tract infection (13%), neurodermatitis (worsening of PN; 13%), back pain (9%), headache (9%), arthralgia (9%), cough (8%), hypertension (8%) and nummular eczema (8%). At week 100, among evaluable patients treated with nemolizumab, 92% achieved PP-NRS4, 86% SD-NRS4, 91% DLQI4, 74% IGA 0/1 and 84% observed healing of >75% of pruriginous lesions. Conclusions: Long-term treatment with nemolizumab was well tolerated and led to disease control with clinically meaningful improvements in itch intensity, pruriginous lesions and quality of life. Clinical Trial Registration No: NCT04204616, RD.06.SPR.202699 and 2019-004294-13 (EudraCT Number).