TMB-001 yields encouraging results in congenital ichthyosis subtypes

A novel isotretinoin ointment formulation to treat congenital ichthyosis subtypes demonstrated promising results in the phase 2b CONTROL study, according to a research letter published in the Journal of the American Academy of Dermatology.

“Hyperkeratosis and widespread scaling are characteristic findings among patients with X-linked recessive (XLRI) or autosomal recessive lamellar (ARCI-LI) congenital ichthyosis (CI) subtypes,” Joyce M.C. Teng, MD, PhD, of Stanford University School of Medicine, and colleagues wrote.

Emollients, keratolytics and off-label retinoids have been used to treat CI.

In the study, TMB-001 (Timber Pharmaceuticals) was investigated in a cohort of participants with ARCI-LI and XLRI. Eligible participants were 9 years or older, had 10% to 90% body surface area involvement, and at least two of four assessment areas with a Visual Index for Ichthyosis Severity (VIIS) score of three or greater. Participants with ARCI-LI comprised 52% of the cohort, while 48% had XLRI.

The analysis included 11 participants who received TMB-001 0.05%, 10 who received TMB-001 0.1% and 12 who received vehicle. Six participants (18%) discontinued treatment.

Sixty-four percent of intent-to-treat participants who received TMB-001 0.05% reached the primary endpoint of VIIS-50 compared with 40% of those who received TMB-001 0.1% and 33% of those who received vehicle reached this endpoint, while for the per protocol analysis, the VIIS-50 rates were 100% for TMB-001 0.05%, 40% for TMB-001 0.1% and 40% for vehicle (TMB-001 0.05% vs. vehicle, P = .04).

Participants in the TMB-001 0.05% group required 28 days to reach VIIS-50 compared with 54 days for the TMB-001 0.1% group and 63.5 days for the vehicle group (TMB-001 0.05% vs. vehicle, P = .02).

Fifty-five percent of participants in the TMB-001 0.05% group reached the endpoint of improvement of at least two points on the Investigators Global Assessment score for intent to treat compared with 40% for the TMB-001 0.1% group and 8% for the vehicle group (TMB-001 0.05% vs. vehicle, P = .002). For the per protocol analysis, the results were 100% for TMB-001 0.05%, 60% for TMB-001 0.1% and 10% for vehicle (TMB-001 0.05% vs. vehicle, P = .002).

A significantly greater proportion of participants in the TMB-001 0.05% group achieved both efficacy endpoints compared with the vehicle group.

Twenty participants (61%) reported treatment-emergent adverse events, the majority of which were application site reactions. Most of the events were mild and occurred within a month of treatment initiation. Overall, safety and tolerability of TMB-001 were consistent with the findings reported in a phase 2a study.

“These results support ongoing TMB-001 efficacy and safety investigation as a promising alternative to oral retinoids for patients with CI,” the study authors wrote.