Neurofibromatosis Type 1

Neurofibromatosis Type 1

NFlection is developing a topical gel containing NFX-179, a proprietary “soft” (metabolically labile) MEK inhibitor for the topical treatment of persistently developing cutaneous neurofibromas (cNF) associated with neurofibromatosis type 1 (NF1).

In a mouse model of NF1, mice given MEK inhibitors for two months showed significant decreases in neurofibroma tumor volume. Additionally, an oral MEK inhibitor is approved for the treatment of plexiform neurofibromas in NF1 patients. Despite promising data demonstrating that oral MEK inhibitors may be efficacious in treating cutaneous neurofibromas, systemic exposure from oral MEK inhibitors commonly leads to significant adverse effects such as severe acneiform rash, diarrhea, nausea, vomiting, edema, fatigue, high blood pressure, cardiomyopathy, and retinal detachment.

NFlection has developed a cosmetically elegant topical formulation of the MEK inhibitor NFX-179 to treat cNFs. NFX-179 has been tested on human cNF explants and has demonstrated dose-dependent suppression of phosphorylated ERK (pERK), a biomarker of Ras/Raf/MEK/ERK pathway activation. In a completed Phase 2a clinical study, NFX-179 Topical Gel suppressed pERK levels in cNFs, and pERK suppression. NFlection recently completed a randomized, double-blind, placebo-controlled Phase 2b study in 199 patients demonstrating the ability of NFX-179 to shrink cNFs more effectively than placebo.