Phase 2a study results demonstrate no concerning safety signals and no evidence of significant systemic exposure to isotretinoin or tretinoin after 12 weeks of treatment with Timber Pharmaceuticals’ topical isotretinoin formulation (TMB-001) in patients with lamellar or X-linked congenital ichthyosis (CI). Findings were presented at the European Academy of Dermatology and Venereology’s (EADV) 30th anniversary congress and reported by Timber.  

Most participants in the study experienced ≥1-grade Investigator Global Assessment (IGA) score reduction and improvement in clinical signs and symptoms of moderate or severe CI. Patients experienced ≥75% improvement of one point from baseline in scaling by IGA measurement and 100% of TMB-001 treated patients were considered to have had their scaling clear, almost clear, or mild by day 57.

The two-part, multicenter, double-blind Phase 2a study evaluated the safety, tolerability, and efficacy of TMB-001 for the treatment of CI in patients greater than 12 years of age. A total of 19 participants were randomized 1:1 to 0.1% or 0.2% concentrations of TMB-001 and were required to have two comparable contralateral treatment areas that covered no more than 6% of body surface and were greater than 150cm2 with identical baseline IGA scores ≥3 (indicating moderate to severe disease severity). Seven participants discontinued the study, including two who discontinued due to treatment-emergent adverse events including mild application site folliculitis and four who withdrew consent from study participation. Other mild or moderate adverse events reported included rash, irritation, pruritus, and pain at the application site as well as contact dermatitis.

In part one of the study, one of the two areas was randomly treated with either concentration of active drug, while the second area was treated with vehicle twice daily for eight weeks. Treatment with 0.1% concentration of TMB-001 led to a greater proportion of participants achieving an improvement in ≥1- and ≥2-grade IGA score versus vehicle (100% vs. 66.7% and 66.7% vs. 33.3%, respectively). For 0.2% concentration of TMB-001, participants receiving active drug achieved similar ≥1- and ≥2-grade IGA improvement versus vehicle (100% vs. 87.5% and 50% vs. 62.5%, respectively). 

By day 57, the proportion of patients with reduction of scaling to clear, almost clear, or mild was higher in patients treated with TMB-001 0.1% or 0.2% when compared with vehicle (100% vs. 55.6% and 100% vs. 87.5%, respectively).

In part two of the study, both areas received the same active treatment for four weeks. Continued active treatment areas were assessed as clear, almost clear, or mild by IGA assessment in 85.7% and 60% of participants for TMB-001 0.1% and 0.2% by day 84, respectively. 

All participants receiving TMB-001 0.1% had ≥1-grade total IGA score reduction versus baseline in both treatment areas, and most patients had ≥2-grade total IGA improvement versus baseline.