Phase 3 Setback for TMB-001 Spurs Hopeful Out-Licensing of Vehicle in Congenital Ichthyosis

TMB-001, a topical isotretinoin formulation, was the first topical retinoid studied for the treatment of moderate to severe congenital ichthyosis (CI) in patients with either autosomal recessive CI or X-linked recessive ichthyosis subtypes.¹ CI encompasses a group of hereditary and often rare skin disorders that result in keratinization, growth restrictions, hearing and eye complications, infections, and thermoregulation.²

To address the unmet need in a debilitating disease such as CI, Timber Pharmaceuticals began the development of TMB-001 and was later acquired by LEO Pharma in 2024 to continue the important work of supporting TMB-001 on a larger, global scale.³

However, in the phase 3 ASCEND trial, there was no statistically significant difference between the proportion of patients treated with TMB-001 responding to treatment after 12 weeks compared with patients treated with vehicle.¹

“We are disappointed and saddened by the results of the phase 3 trial. After encouraging phase 2b results, we observed an unexpectedly high vehicle response in this trial,” said John Koconis, former Chief Executive Officer of Timber Pharmaceuticals, in a news release.¹

Despite the phase 3 trial not meeting its critical end point, a surprising positive opportunity arose for both LEO Pharma and Koconis. According to Louise Broge, Vice President for Program Management, LEO Pharma has received “consistent calls” from clinicians and patient groups to make the vehicle ointment accessible because of the impact experienced by these groups despite the lack of controlled clinical efficacy data. In the best interest of patients affected by CI, LEO Pharma recognized and decided to answer these calls by entering into an agreement with Koconis to out-license the TMB-001 vehicle to be marketed as a cosmetic product.

Considering the rare nature of CI subtypes, Rare Disease Day, recognized on February 28, is an opportunity to raise awareness about the impact and burden of rare diseases, such as CI, on patients and their caregivers. This year’s key message from the Rare Disease Day Organization is “More Than You Can Imagine.”⁴

To further understand the impact of LEO Pharma’s decision, Dermatology Times spoke with Broge about how out-licensing the TMB-001 vehicle is a decision based in patient care, and a step toward “more than patients can imagine.”

Q&A With Louise Broge

Q: Can you provide a brief overview of TMB-001 and its previously intended target for congenital ichthyosis?

Broge: LEO Pharma entered into this partnership for TMB-001 because we want to serve the patients who need us the most. Congenital ichthyosis is such a horrible disease and completely underserved; there is no approved treatment. TMB-001 seemed like a really good candidate: an isotretinoin formulation, traditionally used in congenital ichthyosis, but here the formulation was tailored specifically to congenital ichthyosis patients. It was created in a way that it wouldn't sting, it wouldn't make them itch, and it would be absorbed and feel nice on the skin. It seemed like the perfect drug for these patients, which is why we entered into that partnership.

Q: What did the TMB-001 phase 3 trial reveal about the importance of vehicle formulation in congenital ichthyosis?

Broge: Unfortunately, when we ran the trial and received the results, they showed very clearly that there was no difference between using the vehicle alone and adding the isotretinoin to turn it into a medication. However, it also showed that 40% of patients across both groups reached the criteria where you qualify as a responder, meaning they showed improvement from their baseline symptoms. Of course, we don't know whether another treatment would also have produced that improvement, but it does show that patients improved. And the outcome was the same in both groups.

Q: When the trial missed its primary end point, what signals from clinicians and patients stood out strongly enough to justify moving the vehicle forward?

Broge: The first thing that happened was that the clinicians who participated in the trial were genuinely surprised. They found it hard to believe the results, because they had patients who had seen clear improvements from before the treatment to after the treatment, and so they couldn't believe it at all. As a result clinicians started to ask us, “Are you going to make this vehicle available?” Then, after a little while, the requests from the patients started coming in via emails to various sources. The patient organization, FIRST, also started to request, almost on a regular monthly basis, “Are you going to do something with this? Because patients are asking for it.” And that is what we are doing now.

Q: How should clinicians think about positioning this vehicle in practice, given that it will be available without clinical efficacy claims?

Broge: 40% of the patients responded. But of course, we cannot compare it with anything else, and therefore, we don't know what caused that response. It is well known that emollients and ointments like the TMB-001 vehicle are used in congenital ichthyosis. These patients have no approved treatment, so they are doing what they can to deal with their symptoms. This vehicle should be positioned in the same way.

Q: In a disease with limited tolerable topical options, how much did patient experience and real-world need factor into this decision?

Broge: That was a deciding factor, definitely. When you start getting experience from the clinicians of what they have seen, and you also start getting the patient requests, then this is what a company like LEO Pharma does. We want to help the patients who really need us, so therefore, we had to find a way where the patients could access it.

Q: Why was out-licensing to a focused partner the fastest and most compliant way to make this vehicle available?

Broge: You could say, “Why couldn't we just produce this ourselves,” especially now that we already had done a trial with this product. But, we are not experts in producing, selling, marketing, and distributing emollients and other non-medicinal products. Our expertise lies in medical dermatology. We quite strongly believe, and the industry is increasingly recognizing, that the best way to reach patients is for each player to focus on what they're best at. We focus on medical dermatology, while others have the expertise and infrastructure to get emollients to the patients, which is why we partner with them to make the product available in the fastest and most compliant way.

Q: Do you see this as a potential model for how industry can responsibly respond when a trial falls short but still uncovers patient value?

Broge: It is definitely the way forward. The key is to understand the real need, and then you assess whether you are the right organization to meet that need. If not, it is about considering how the need can still be addressed. That may be collaborating with others who are better positioned to do so.

Do you have experience with TMB-001 or your patients requesting it? Email [email protected] for an opportunity to be featured.

References

1. Timber Pharmaceuticals, Inc., a LEO Pharma Company, provides an update on the development program for TMB-001 in congenital ichthyosis. News release. LEO Pharma. August 21, 2024. Accessed February 23, 2026. https://www.leo-pharma.com/media-center/news/2024-timber-pharmaceuticals-provides-an-update
2. Lilly E, Bunick CG. Congenital ichthyosis: a practical clinical guide on current treatments and future perspectives. Clin Cosmet Investig Dermatol. 2023;16:2473-2479. doi:10.2147/CCID.S388608
3. LEO Pharma finalizes acquisition of key assets from Timber Pharmaceuticals. News release. LEO Pharma. January 23, 2024. Accessed February 23, 2026. https://www.leo-pharma.com/media-center/news/2023-leo-pharma-finalizes-acquisition
4. Rare Disease Day 2026 information pack. Rare Disease Day. Accessed February 23, 2026. https://download2.rarediseaseday.org/2026/Info_pack/Info_pack.pdf