Topical Isotretinoin Shows Promise in Phase 3 ASCEND Trial for Congenital Ichthyosis

A recent study, presented in a poster at the 2024 Society for Pediatric Dermatology Annual Meeting in Toronto, ON, reported that pediatric patients with moderate to severe X-linked and autosomal recessive congenital ichthyosis who were treated with TMB-001 0.05%, a topical isotretinoin formulation, exhibited notable improvements in skin symptoms and minimal systemic side effects.¹

According to poster authors Lee et al, current treatment options for congenital ichthyosis are limited, with no topical treatments approved by major regulatory agencies such as the European Medicines Agency or US Food and Drug Administration. Oral acitretin, though used off-label in some cases, poses safety concerns, particularly for long-term use in children, they noted.

Background and Methods

The ASCEND trial (NCT05295732)² represents the first phase 3 study investigating TMB-001 0.05% in patients aged 6 years and older with moderate to severe congenital ichthyosis. The trial enrolled 110 participants with various genotypes of X-linked (XLRI) and autosomal recessive (ARCI) forms of congenital ichthyosis, aiming to assess both efficacy and safety.

Findings

Participants in the ASCEND trial underwent a maximal use regimen of TMB-001 0.05%, applying the topical treatment twice daily to 75-90% of their body surface area for 14 days. Pharmacokinetic studies revealed steady-state mean peak plasma concentrations of isotretinoin, 4-oxo-isotretinoin, and tretinoin, with minimal systemic absorption observed.

By week 12, significant improvements in Investigator's Global Assessment scores were noted, with an average decrease from baseline scores indicating reduced scaling and fissuring of the skin. Approximately 82% of participants achieved at least a 1-point improvement in IGA scores, demonstrating the clinical efficacy of TMB-001 0.05% in managing congenital ichthyosis symptoms.

The study also reported a favorable safety profile for TMB-001 0.05%, with local skin reactions being the most common adverse events observed. These reactions, predominantly mild to moderate in intensity, were manageable and resolved without severe systemic side effects reported. No serious adverse events or treatment-related complications were documented during the trial period.

Conclusions

"Preliminary results from subjects with moderate to severe RXLI or ARCI treated maximally with TMB-001 0.05% (BID for 14 days to 75-90% BSA) demonstrate promising efficacy, acceptable safety, and low systemic ISO/4-O-ISO/TR/4-O-TR concentrations," wrote poster authors.

Further validation in larger cohorts and longer-term studies will be crucial to confirm these early results and establish TMB-001's place in the therapeutic landscape for congenital ichthyosis, according to Lee et al.

References

1. Lee LW, Blume-Peytavi U, Schneider H, et al. Efficacy, safety and pharmacokinetics of first 17 adolescent and adult subjects in maximal use/ phase 3 ASCEND trial of topical isotretinoin (TMB-001 0.05%) for treatment of X-linked and autosomal recessive congenital ichthyosis. Poster presented at the 2024 Society for Pediatric Dermatology Annual Meeting, July 11-14; Toronto, ON.
2. ClinicalTrials.gov. Identifier NCT05295732. Available from: https://clinicaltrials.gov/ct2/show/NCT05295732