Timber Pharmaceuticals announced the online publication of a sub-analysis of the Phase 2b CONTROL study, which is evaluating TMB-001, a topical isotretinoin formulated using the company’s patented IPEG delivery system, in subjects 9 years of age and older with moderate to severe congenital ichthyosis (CI). The study was published in Clinical and Experimental Dermatology (CED). 

The sub-analysis was designed to assess whether the efficacy and safety of TMB-001 differed between subjects with autosomal recessive congenital ichthyosis (ARCI) and X-linked recessive ichthyosis (XLRI). Results show that treatment with TMB-001 demonstrated greater proportions of participants achieving the primary and key secondary endpoints versus vehicle regardless of the subtype of CI.

“Patients with severe CI must often combine bathing, mechanical scale removal, and topical over-the-counter emollient therapy with the possible addition of systemic retinoid therapy throughout their lifetimes to address their disease, sometimes without significant improvement,” Christopher Bunick, MD, PhD, Associate Professor of Dermatology at Yale University School of Medicine and corresponding author of the paper, said in a company news release. “In this sub-analysis, participants in the CONTROL study with ARCI and XLRI mostly showed comparable percentage differences in responses to treatment with a novel topical isotretinoin formulation versus vehicle. That is especially encouraging because systemic retinoids do not typically demonstrate the same efficacy across subtypes of CI.”

A total of 33 participants in the CONTROL study were randomized to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily, stratified by CI subtype, for 12 weeks. The primary endpoint was the proportion of participants with a 50% or greater reduction versus baseline in Visual Index for Ichthyosis Severity (VIIS) scaling. The key secondary endpoint was a two-grade or greater reduction in Investigator Global Assessment (IGA) scaling score versus baseline. Adverse events (AEs) were monitored. Among enrolled participants (TMB-001 0.05% [n = 11], TMB-001 0.1% [n = 10], and vehicle [n = 12]), 52% had ARCI and 48% had XLRI subtypes. The intent-to-treat (ITT) population consisted of all randomized participants who received one or more doses of the study medication. The per-protocol (PP) population included all participants who met all inclusion criteria, were treatment compliant (≥80%–120% of study drug applied), had a VIIS scaling measurement at the end of Week 12, and had no major protocol violations.

• In the ITT population, 33%/50%/17% of participants with ARCI and 100%/33%/75% of participants with XLRI who received TMB-001 0.05%/TMB-001 0.1%/vehicle, respectively, achieved VIIS-50.
• In the PP population, 100%/33%/17% of participants with ARCI and 100%/50%/75% of participants with XLRI who received TMB-001 0.05%/TMB-001 0.1%/vehicle, respectively, achieved VIIS-50.
• In the ITT population, improvement of ≥2-grade IGA score was observed in 33%/50%/0% of participants with ARCI and 83%/33%/25% of participants with XLRI who received TMB-001 0.05%/TMB-001 0.1%/vehicle, respectively.
• In the PP population, improvement of ≥2-grade IGA score was observed in 100%/67%/0% of participants with ARCI and 100%/50%/25% of participants with XLRI who received TMB-001 0.05%/TMB-001 0.1%/vehicle, respectively.
• Most AEs reported were application site reactions and were similarly distributed among both subgroups.

“ARCI and XLRI are severe subtypes of CI that can lead to cutaneous manifestations including large, dark scaling throughout the body and reduced quality of life,” said Alan Mendelsohn, MD, Chief Medical Officer of Timber. “This 12-week analysis demonstrated TMB-001 reduced clinical signs and symptoms of two forms of CI and was well tolerated in participants with either ARCI or XLRI. TMB-001 has been granted orphan designation for both of these subtypes of CI by the European Commission, and the findings of this sub-analysis support our efforts to evaluate TMB-001 in a currently ongoing pivotal Phase 3 clinical trial. We look forward to advancing this program with the goal of delivering a promising alternative to systemic retinoids for patients with these two especially severe forms of CI.”