New TMB-001 Sub-Analysis Data Published in Clinical and Experimental Dermatology

Data from a sub-analysis of Timber Pharmaceuticals’ phase 2b CONTROL study evaluating the safety and efficacy of TMB-001 for the treatment of congenital ichthyosis (CI) was recently published online in Clinical and Experimental Dermatology.¹ In the 12-week analysis, TMB-001, a topical isotretinoin, reduced signs and symptoms of autosomal recessive congenital ichthyosis (ARCI) and X-linked recessive ichthyosis (XLRI) and was well-tolerated among patients.

In a recent interview with Dermatology Times®, Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine and principal investigator of the CI trials at Yale University, noted, “Physically, patients with ichthyoses generally produce a lot of scale. This scale can cover many parts, if not all parts, of their body and in moderate-to-severe cases, the scale can be thick and constantly shedding. This presents an aesthetic problem, where other people clearly recognize the scale and that the person has a ‘disease’, and this feeds into the emotional challenges...There is never a resting moment when someone isn't looking or judging their skin.”

Thirty-three patients participated in the CONTROL study and were randomized to TMB-001 0.05% (n=11), TMB-001 0.1% (n=10), or a twice daily vehicle (n=12), divided by CI subtype, for 12 weeks. CONTROL’s primary endpoint was the proportion of patients with a 50% or greater reduction versus baseline in Visual Index for Ichthyosis Severity (VIIS) scaling. The key secondary endpoint was a 2-grade or greater reduction in Investigator Global Assessment (IGA) scaling score versus baseline. Out of the 33 enrolled patients, 52% had ARCI and 48% had XLRI subtypes.

The intent-to-treat (ITT) population included all randomized patients who received one or more doses of the study medication. The per-protocol (PP) population included all patients who met the inclusion criteria, complied with treatment (≥80%–120% of study drug applied), had a VIIS scaling measurement at the end of week 12, and had no major protocol violations.

Key results from CONTROL include:

• In the ITT population, 33%/50%/17% of patients with ARCI and 100%/33%/75% of patients 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 patients with ARCI and 100%/50%/75% of patients 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 patients with ARCI and 83%/33%/25% of patients 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 patients with ARCI and 100%/50%/25% of patients with XLRI who received TMB-001 0.05%/TMB-001 0.1%/vehicle, respectively
• Most reported adverse events were application site reactions and were similar across both subgroups

Alan Mendelsohn, MD, chief medical officer of Timber Pharmaceuticals, noted that TMB-001 has been granted orphan designation for ARCI and XLRI subtypes by the European Commission, and the recent data from the sub-analysis supports Timber’s evaluation of TMB-001 in its current pivotal phase 3 clinical trial.

Reference

1. Timber Pharmaceuticals announces publication of sub-analysis of phase 2b CONTROL study in Clinical and Experimental Dermatology. Timber Pharmaceuticals. Published March 20, 2023. Accessed March 22, 2023. https://www.globenewswire.com/news-release/2023/03/20/2630210/0/en/Timber-Pharmaceuticals-Announces-Publication-of-Sub-Analysis-of-Phase-2b-CONTROL-study-in-Clinical-and-Experimental-Dermatology.html