Timber Pharmaceuticals Meets with FDA on TMB-001 End-of-Phase 2 Trial

Timber Pharmaceuticals, Inc, a biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases, announced the successful completion of an end-of-phase 2 meeting with the FDA that resulted in a clear path to progress to a pivotal phase 3 study for its lead asset, TMB-001, a topical isotretinoin formulated using the company’s patented IPEG delivery system.

Thephase 2b CONTROL study (NCT04154293) evaluating TMB-001 in moderate to severe congenital ichthyosis (CI),was completed in September 2021.The data demonstrated clinically meaningful efficacy with a favorable safety profile, according to the release. Based on FDA feedback at the end-of-phase 2 meeting, Timber plans to start a pivotal phase 3 study of TMB-001 in the second quarter of 2022.

“We are pleased to have successfully completed our end-of-phase 2 meeting with the FDA and are committed to delivering a potential new option as rapidly as possible for the treatment of CI to patients who currently have no FDA-approved treatments available,” said John Koconis, chairman and chief executive officer of Timber. “The full data set from our phase 2b CONTROL study indicates that TMB-001 may be a promising topical alternative to oral retinoids and fully supports initiating phase 3 investigation. We now have a clear path forward for TMB-001 based on guidance from the FDA and, with the completion of a recent financing, look forward to the initiation of a robust phase 3 trial in the coming months.”

CI is a group of rare genetic keratinization disorders that leads to dry, thickened, and scaling skin, the release explained. Patients with moderate to severe subtypes of CI, like X-linked ichthyosis (XLRI) and autosomal recessive congenital ichthyosis (ARCI), which includes lamellar ichthyosis (LI), often have considerable hyperkeratosis and skin scaling. There are currently no approved FDA treatments for these conditions.

Phase 2b CONTROL study data presented at the 2022 Winter Clinical Dermatology Conference

The randomized, parallel, double-blind, vehicle-controlled phase 2b CONTROL study was designed by researchers to evaluate the efficacy and safety of 2different concentrations of TMB-001 in patients with LI or XLRI. There were 33 patients randomized (1:1:1 ratio) to receive either TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily, grouped by CI subtype, for 12 weeks. The intent-to-treat (ITT) population included all patients initially enrolled in the trial, and the per-protocol (PP) population included patients who completed the full 12 weeks of treatment, the release stated.

Timber has chosen to use the 0.05% dose of TMB-001 for is phase 3 program based on the data from this study. The median response to treatment time with TMB-001 0.05% in the ITT was 28 days compared to 63.5 days for vehicle and there were no safety signals of concern between the groups, according to the release. Also, the patients being treated by TMB-001 on average demonstrated statistically significant rapid relief of scaling and fissuring, with half of the patients demonstrating relief in 28 days or less.

The primary efficacy endpoint of the study was the proportion of patients who achieved a Visual Index for Ichthyosis Severity(VIIS)-50 or a 50% reduction in the VIIS score vs baseline. The VIIS scoring system examines 4 areas of the body to evaluate improvement in scaling alone.

For the PP population:

Of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle,100%, 40%, and 40% achieved VIIS-50, respectively (P=.04 for TMB-001 0.05% vs vehicle).

For the ITT population:

Of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle,64%, 40%, and 33% achieved VIIS-50, respectively (P=.17 for TMB-001 0.05% vs vehicle).

The secondary efficacy endpoint was the proportion of patients who achieved Investigator Global Assessment (IGA) treatment success defined as a 2-point reduction in scaling and fissuring severity over all treated areas of the body.

For the PP population:

Of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle 100%, 60%, and 10%, respectively, reported agreater than or equal to2-grade IGA score improvement (P=.002 for TMB-001 0.05% vs vehicle).

For the ITT population:

Of patients receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, improvement ofa greater than or equal to 2-grade IGA score was observed in 55%, 40%, and 8%, respectively (P=.02 for TMB-001 0.05% vs vehicle).

Treatment-emergent adverse events (TEAEs) included local skin reactions that were mild or moderate in severity, and no serious adverse events (SAEs) were observed, according to the release.

“These data demonstrate clinically meaningful efficacy for the participants as well as significantly more rapid improvement in the participants who received the TMB-001 0.05% treatment,” said Alan Mendelsohn, MD, chief medical officer of Timber. “We thank our investigator community and the participants in our study for assisting us to advance this promising therapy forward.”

Reference:

1. Timber pharmaceuticals announces positive end-of-phase 2 meeting with FDA for tmb-001 in moderate to severe congenital ichthyosis. GlobeNewswire News Room. Published March 2, 2022. Accessed February 14, 2022. https://www.globenewswire.com/news-release/2022/02/03/2378451/0/en/Timber-Pharmaceuticals-Announces-Positive-End-of-Phase-2-Meeting-with-FDA-for-TMB-001-in-Moderate-to-Severe-Congenital-Ichthyosis.html