Positive Results from Phase 2b Study of TMB-001 for Congenital Ichthyosis

Results from Timber Pharmaceuticals’ phase 2b CONTROL study of TMB-001, a topical isotretinoin to treat moderate-to-severe congenital ichthyosis (CI), were published in the Journal of the American Academy of Dermatology.¹ Timber Pharmaceuticals is a biopharmaceutical company that develops therapies for rare and orphan dermatologic diseases.

The published results² showed that in the per protocol (PP) population, 100%, 40%, and 40% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle achieved the primary endpoint, which was a 50% reduction in the Visual Index for Ichthyosis Severity (VIIS) scale score (or VIIS-50) versus baseline (P= 0.04 for TMB-001 0.05% vs. vehicle). In the intent-to-treat (ITT) population, 64%, 40%, and 33% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle achieved VIIS-50 (P = 0.17 for TMB-001 0.05% vs. vehicle).

The secondary efficacy endpoint measured the difference in the percentage 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. In the PP population, 100%, 60%, and 10% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle reported a ≥2-grade IGA score improvement (P= 0.002 for TMB-001 0.05% vs vehicle). In the ITT population, improvement of ≥2-grade IGA score was observed in 55%, 40%, and 8% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle (P= 0.02 for TMB-001 0.05% vs vehicle).

The randomized, parallel, double-blind, vehicle-controlled phase 2b CONTROL study evaluated the efficacy and safety of 2 concentrations of TMB-001 in patients with X-linked recessive (XLRI) or autosomal recessive lamellar (ARCI-LI) subtypes of CI. In total, 33 patients were randomly selected to receive either TMB-001 0.05%, TMB-001 0.1%, or vehicle 2 times a day, layered with CI subtype, for 12 weeks. The ITT population included all patients initially enrolled in the trial, and the PP population included all patients who completed the total 12 weeks of treatment. Patient-reported adverse events include local skin reactions that were mild to moderate. No serious adverse events have been reported.

Timber Pharmaceuticals has announced the initiation of the pivotal phase 3 ASCEND study to evaluate the efficacy, safety, and pharmacokinetics of TMB-001 0.05% for the treatment of moderate-to-severe forms of CI in patients aged 6 years or older.

CI affects approximately 80,000 people in the US and leads to cutaneous manifestations of large, dark scaling throughout the body.

References:

1. Timber pharmaceuticals announces publication of results from phase 2b control study of FDA-designated breakthrough therapy TMB-001 in the Journal of the American Academy of Dermatology. GlobeNewswire News Room. Published August 26, 2022. Accessed August 26, 2022. https://www.globenewswire.com/news-release/2022/08/26/2505296/0/en/Timber-Pharmaceuticals-Announces-Publication-of-Results-from-Phase-2b-CONTROL-Study-of-FDA-Designated-Breakthrough-Therapy-TMB-001-in-the-Journal-of-the-American-Academy-of-Dermato.html
2. Teng J, Bunick C, et al. 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. JAMA Dermatol. Published online July 20, 2022. doi:10.1016/j.jaad.2022.07.028