Alan M. Mendelsohn, MD, Executive Vice President and Chief Medical Officer at Timber Pharmaceuticals, discusses the positive clinical data from the completed phase 2b CONTROL study of TMB-001, an investigational treatment for congenital ichthyosis. These data were recently presented at the 31st European Academy of Dermatology and Venereology (EADV) Congress 2022.
Congenital ichthyosis is a rare genetic skin disorder characterized by dry, thickened, and scaling skin. Individuals with this condition may experience limited range in motion, chronic itching, an inability to sweat, and increased risk of infections.
TMB-001 is a topical isotretinoin that has been formulated using the Timber’s patented IPEG™ delivery system, for the treatment of moderate to severe forms of congenital ichthyosis.
As Dr. Mendelsohn explains, Timber Pharmaceuticals recently presented 7 abstracts detailing positive clinical data from the completed phase 2b CONTROL study at EADV 2022. The CONTROL study was a randomized, double-blind, vehicle-controlled study designed to assess the efficacy and safety of two concentrations of TMB-001 (0.05% and 0.1% isotretinoin) for the treatment of two distinct subtypes of moderate-to-severe congenital ichthyosis (X-linked recessive and lamellar ichthyosis) in patients 9 years old or older. Subjects applied TMB-001 twice daily for 12 weeks. The primary endpoint was the reduction of targeted ichthyosis severity, determined by a ≥50% reduction in the validated Visual Index for Ichthyosis Severity (VIIS) scaling score. Secondary endpoints included reduction in overall ichthyosis severity, as measured by a two-point improvement using the Investigator Global Assessment (IGA) scale.
Topline results from the CONTROL trial were announced October 2021 and demonstrated that TMB-001 0.05% was significantly more effective in reducing disease severity in patients with moderate-to-severe congenital ichthyosis compared to vehicle alone. Additionally, TMB-001 was found to be well-tolerated.
Highlights from the data presented at EADV 2022 include:
• Age, gender, and body mass index did not significantly influence response rates to TMB-001.
• Participants who had up to 3 drug interruptions lasting up to a week due to difficulty tolerating TMB-001 were still able to respond to the drug 50-75% of the time.
• All (100%) patients who did not require a drug interruption responded to treatment with TMB-001.
• Skin reactions to TMB-001 typically occurred within the first 2-4 weeks of treatment.
• Disease subtype (X-linked or lamellar ichthyosis) did not impact efficacy of TMB-001
• In the cohort treated with TMB-001 0.05%, none of the patients had any abnormalities in their blood counts or platelets, nor significant liver damage, nor changes in cholesterol levels.
• The commonly used quality of life questionnaire, Dermatology Life Quality Index, may not be the best tool as it may underestimate the burden of disease on these patients’ lives.
The data presented at EADV 2022 have informed the study design of the phase 3 ASCEND clinical trial, which is evaluating TMB-001 in the same subtypes of congenital ichthyosis.
