HSP90 inhibitor RGRN‐305 for oral treatment of plaque‐type psoriasis: efficacy, safety and biomarker results in an open‐label proof‐of‐concept study

HSP90 is a downstream regulator of tumour necrosis factor (TNF)‐α and interleukin (IL)‐17A signalling and may serve as a novel target in the treatment of psoriasis. This phase Ib proof‐of‐concept study was undertaken to evaluate the safety and efficacy of a novel HSP90 inhibitor (RGRN‐305) in treating plaque psoriasis. Six of the 11 patients who completed the study responded to RGRN‐305 with a PASI improvement between 71% and 94%, whereas five patients were considered nonresponders with a PASI response < 50%. No severe adverse events were reported. Four of seven patients treated with 500 mg RGRN‐305 daily experienced a mild‐to‐moderate exanthematous drug‐induced eruption owing to the study treatment. Two patients chose to discontinue the study because of this exanthematous eruption. RGRN‐305 treatment resulted in pronounced inhibition of the IL‐23, TNF‐α and IL‐17A signalling pathways and normalization of both histological changes and psoriatic lesion gene expression profiles in patients who responded to treatment. Treatment with RGRN‐305 showed acceptable safety, especially in the low‐dose group, and was associated with clinically meaningful improvement in a subset of patients with plaque psoriasis, indicating that HSP90 may serve as a novel future target in psoriasis treatment.