Maximal use of 0.05% topical isotretinoin in patients with congenital ichthyosis results in low systemic exposure

Congenital ichthyoses (CI) are rare, inherited skin disorders characterized by hyperkeratosis, scaling and fissuring that significantly impair patients' quality of life. Treatment options are limited, with systemic retinoids reserved for severe cases owing to their adverse effect profile. This open-label, single-arm, maximal-use trial investigated the systemic exposure and safety of a topically administered isotretinoin ointment (TMB-001 0.05%) in patients with moderate-to-severe CI. Thirty-four patients aged ≥6 years applied TMB-001 0.05% under maximal-use conditions (twice daily to 75%-90% of the body surface area) for 14 days, with continued application for another 10 weeks. Exposure levels for TMB-001 0.05% and its metabolites were < 1% of those observed after single oral administration of 80 mg isotretinoin to healthy adults. A majority of patients had local safety or tolerability issues, most of which were mild. Overall, the treatment was well tolerated with no evidence of systemic toxicity.