Timber Pharmaceuticals, Inc. (“Timber” or the “Company”) (NYSE American: TMBR), a clinical-stage biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases, announced that results from the previously completed Phase 2b CONTROL study that evaluated TMB-001, a topical isotretinoin formulated using the Company’s patented IPEG™ delivery system, in moderate to severe congenital ichthyosis (CI) are published in the Journal of the American Academy of Dermatology.
The paper, titled, “The CONTROL study: A randomized, double-blind vehicle-controlled Phase 2b study of novel topical isotretinoin formulation demonstrates improvement in recessive X-linked and autosomal recessive lamellar congenital ichthyosis,” highlights results that were initially announced by Timber in September 2021 demonstrating clinically meaningful efficacy with a favorable safety profile.
“The opportunity to publish these data in a world-renowned journal reviewed by our peers in rare and orphan dermatologic diseases exemplifies the significance of our clinical development program and the potential we have to change the treatment landscape for people living with CI,” said Alan Mendelsohn, M.D., Chief Medical Officer of Timber. “Based on the success of the Phase 2b CONTROL study, we have already enrolled the first patients in the recently launched Phase 3 ASCEND clinical trial that is designed to provide the pivotal data we need to navigate the regulatory review process. We want to thank all prior and current investigators and patients who have helped us get to this point.”
The randomized, parallel, double-blind, vehicle-controlled Phase 2b CONTROL study was designed to evaluate the efficacy and safety of two concentrations of TMB-001 in patients with X-linked recessive (XLRI) or autosomal recessive lamellar (ARCI-LI) subtypes of CI that affect about 80,000 people in the U.S. and lead to cutaneous manifestations that include large, dark scaling throughout the body.
A total of 33 patients were randomized (1:1:1 ratio) to receive either TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily, stratified by CI subtype, for 12 weeks. The intent-to-treat (ITT) population included all patients initially enrolled in the trial, and the per-protocol (PP) population included patients who completed the full 12 weeks of treatment.
The primary efficacy endpoint was the difference in the proportion of TMB-001 and vehicle treated patients with Visual Index for Ichthyosis Severity (VIIS)-scaling treatment success (VIIS-50 or a 50% reduction in the VIIS score versus baseline).
- For the PP population, 100%, 40%, and 40% of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle achieved VIIS-50, respectively (P = 0.04 for TMB-001 0.05% vs. vehicle).
- For the ITT population, 64%, 40%, and 33% of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle achieved VIIS-50, respectively (P = 0.17 for TMB-001 0.05% vs. vehicle).
The key secondary efficacy endpoint was the difference in the proportion of patients who achieved Investigator Global Assessment (IGA) treatment success (≥2-grade reduction in scaling and fissuring severity over all treated areas of the body) comparing TMB-001 to vehicle.
- For the PP population, 100%, 60%, and 10% of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively, reported a ≥2-grade IGA score improvement (P = 0.002 for TMB-001 0.05% vs vehicle).
- For the ITT population, improvement of ≥2-grade IGA score was observed in 55%, 40%, and 8% of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively (P = 0.02 for TMB-001 0.05% vs vehicle).
Treatment-emergent adverse events included local skin reactions that were mild or moderate in severity, and no serious adverse events were observed.
“Hyperkeratosis and widespread scaling are characteristic findings among patients with XLRI or ARCI-LI subtypes of CI, and current management predominantly includes emollients, keratolytics, and off-label retinoids,” said lead author Joyce M.C. Teng, M.D., Ph.D., Professor and Director of Pediatric Dermatology, Stanford University. “These results support ongoing TMB-001 efficacy and safety investigation as a promising alternative to oral retinoids for patients with CI.”
Timber has since announced the initiation of the pivotal Phase 3 ASCEND clinical trial that is evaluating the efficacy, pharmacokinetics and safety of TMB-001 0.05% for the treatment of moderate to severe forms of CI in subjects 6 years of age and older. More here.