Leo Pharma's Timber trial fails in Phase III

Leo Pharma has faced a setback in its dermatology division following the failure of its lead asset, TMB-001, in a Phase III clinical trial. TMB-001, a topical ointment containing isotretinoin, was being tested for treating moderate to severe congenital ichthyosis—a group of inherited skin conditions characterized by dry, scaly skin. This trial, known as the ASCEND trial (NCT05295732), did not show statistically significant improvements in patients using TMB-001 compared to those using a placebo, failing to meet both its primary and key secondary endpoints.

According to a press release from Leo Pharma on August 21, the results do not justify pursuing a regulatory submission in the United States. As of now, there are no FDA-approved treatments for ichthyosis, and the condition is typically managed with hydrating creams and lotions.

The ASCEND trial included three phases: a three-week induction period, a nine-week treatment phase, and a 12-week open-label maintenance phase for eligible patients. A total of 209 participants, aged six years and older, were enrolled in the study. Timber Pharmaceuticals' CEO, John Koconis, expressed disappointment over the trial's outcome, particularly after promising results from a previous Phase IIb trial where TMB-001 showed a 50% reduction in the Visual Index for Ichthyosis Severity scale compared to baseline.

In August 2023, Leo Pharma acquired Timber Pharmaceuticals for $36 million, including an upfront payment of $14 million. At the time of acquisition, Timber had received orphan, fast-track, and breakthrough therapy designations from the FDA. Following the acquisition, Timber became a wholly-owned subsidiary of Leo Pharma. Chief Development Officer Kreesten Meldgaard Madsen emphasized that while Leo Pharma remains committed to addressing dermatologic diseases, not every clinical trial ends in success.

Despite the setback with TMB-001, Leo Pharma’s financial outlook for 2024 remains unaffected. The company achieved a regulatory milestone in June with the FDA approval of Adbry (tralokinumab-ldrm), a single-dose autoinjector for treating atopic dermatitis. Meanwhile, Timber Pharmaceuticals continues to develop TMB-003 (sitaxentan), a topical ETA receptor antagonist currently in preclinical testing for sclerotic skin diseases.

The failure of the TMB-001 trial underscores the challenges inherent in pharmaceutical research and development, particularly in dermatology. Leo Pharma's persistence in the field highlights the ongoing need for effective treatments for complex skin conditions like ichthyosis.