Timber Pharmaceuticals has posted midphase trial data on its topical Accutane treatment for the rough, dry and scaly skin of congenital ichthyosis patients, setting it up to start a pivotal study next year.
Systemic isotretinoin, the active ingredient in Accutane, is already used to treat ichthyosis. Patagonia Pharmaceuticals created a topical formulation that is designed to minimize systemic absorption of the drug, which is subject to a risk evaluation and mitigation strategy because of side effects when it is given systemically. Having picked up rights to the formulation for $50,000 upfront, Timber has now released data from a phase 2 trial.
Investigators randomized 33 patients with moderate-to-severe congenital ichthyosis aged nine years and up to apply one of two concentrations of TMB-001 or placebo twice a day for 12 weeks. At the end of the treatment period, 64% of patients on low-concentration TMB-001 had experienced a 50% or greater improvement on a visual index of disease severity—the primary endpoint—compared to 33% of their peers in the control cohort.
Timber CEO John Koconis hailed the trial as a success. “The study was not powered or intended to show statistical significance, but we demonstrated clinically meaningful efficacy with a favorable safety profile that support the continued development of our lead product candidate,” Koconis said in a statement.
The nominal p value for the primary endpoint was 0.17. TMB-001 performed better in a per-protocol analysis, in which all subjects on the low dose had a 50% or greater improvement, but researchers usually use the more conservative intention-to-treat approach that includes all randomized patients.
Timber presented both types of analysis of a secondary endpoint that looked at the proportion of patients who experienced a two grade or greater improvement in Investigator Global Assessment. As with the primary endpoint, there was a big difference between the two analyses, with all subjects in the per-protocol dataset meeting the endpoint versus 55% of the intention-to-treat population. Only 8% of subjects in the control group experienced a two grade or greater improvement.
The results and limitations of the study leave questions about the efficacy of TMB-001 unanswered. Timber has seen enough to outline plans to answer those questions, though, with talks with the FDA and the start of a phase 3 study on its schedule for the first half of next year.