%0 Journal Article
%T Effect of NFX-179 MEK inhibitor on cutaneous neurofibromas in persons with neurofibromatosis type 1.
%A Sarin KY
%A Bradshaw M
%A O'Mara C
%A Shahryari J
%A Kincaid J
%A Kempers S
%A Tu JH
%A Dhawan S
%A DuBois J
%A Wilson D
%A Horwath P
%A de Souza MP
%A Powala C
%A Kochendoerfer GG
%A Plotkin SR
%A Webster GF
%A Le LQ
%J Sci Adv
%V 10
%N 18
%D 2024 May 3
%M 38691597
%F 14.957
%R 10.1126/sciadv.adk4946
%X This phase 2a trial investigated the efficacy of NFX-179 Topical Gel, a metabolically labile MEK inhibitor, in the treatment of cutaneous neurofibromas (cNFs) in neurofibromatosis type 1. Forty-eight participants were randomized to four treatment arms: NFX-179 Topical Gel 0.05%, 0.15%, and 0.5% or vehicle applied once daily to five target cNFs for 28 days. Treatment with NFX-179 Topical Gel resulted in a dose-dependent reduction in p-ERK levels in cNFs at day 28, with a 47% decrease in the 0.5% NFX-179 group compared to the vehicle (P = 0.0001). No local or systemic toxicities were observed during the treatment period, and systemic concentrations of NFX-179 remained below 1 ng/ml. In addition, 20% of cNFs treated with 0.5% NFX-179 Topical Gel showed a ≥50% reduction in volume compared to 6% in the vehicle group by ruler measurement with calculated volume (P = 0.021). Thus, NFX-179 Topical Gel demonstrated significant inhibition of MEK in cNF with excellent safety and potential therapeutic benefit.