TMB-001 showed positive results in the reduction of congenital ichthyosis severity in a phase 2b CONTROL study.
Alan Mendelsohn, MD, and CMO of Timber Pharmaceuticals in Basking Ridge, New Jersey, discusses recently published study data and abstracts on TMB-001, a topical isotretinoin, for the treatment of congenital ichthyosis. Seven abstracts from Timber Pharmaceuticals were presented at the 31st Annual European Academy of Dermatology and Venereology in Milan, Italy.
Alan Mendelsohn, MD: Hello from Milan. My name is Alan Mendelsohn. I am the Chief Medical Officer of Timber Pharmaceuticals, and I am attending the European Academy of Dermatology and Venereology meetings here, where we have just recently presented 7 abstracts on our control phase 2b study of topical TMB-001, which is a topical isotretinoin compound using proprietary IPEG or polyethylene glycol vehicle mixture in the treatment of x-linked and lamellar ichthyosis. I’m really happy to be at the meeting, really happy to see the advances that are being made, frankly, proudly by Timber. There were 12 abstracts at this meeting on congenital ichthyosis, and 7 of the 12 abstracts came from Timber and support the reasons why we currently have fast track designation and breakthrough designation by the FDA for this compound.
Just to briefly go over the control trial the phase 2b trial itself, this was a 34-patient phase 2b trial, 1-1-1 randomization of low dose TMB-001 0.05%, higher dose 0.1%, and vehicle. In patients 9 years and above, with either x-linked or lamellar ichthyosis, not just the TGM-1 type, but really any of the 8 or 9 other genetic abnormalities which differentiates this trial from potentially other trials. The primary endpoint of the trial was an improvement of 50% in theVIIS or Visual Index for IchthyosisSeverity score. And the major secondary endpoint was a two-point improvement in the IGA or Investigator Global Assessment. What we found in a presented previously in the Journal of the American Academy of Dermatology is a marked improvement clinically and statistically for those patients who received 0.5% dose compared to vehicle with a very, very tolerable safety profile that really only involve localized skin reactions.
At this meeting, we focused on two different areas of research, the first of which really tries to define best from the trial data which population of patients do best. And then the second area that we looked at, it's really just general information and knowledge that can be used to advance the use of isotretinoin in future trials by us and other companies around isotretinoin utility in congenital ichthyosis. What we reported at this meeting is that basically, age, gender, and body mass index really did not influence response rates to the topical isotretinoin, TMB-001. Patients who responded tend to have slightly less body surface area involvement, but tended to have worse quality of life measurements and worse itch at baseline. So that's a good thing in terms of physicians and health professionals being able to choose the proper patients. We showed that, even though it's well known that patients who receive topical retinoids will have an increased risk of skin reactions and may have to stop and take drug holidays, that, in fact, the vast majority of patients, up to even 3 drug interruptions during the first 12 weeks still have a 50% to 75% chance of fully responding by week 12. And in fact, with no drug interruptions, 100% of those patients respond. And so we've incorporated that into our phase 3 program in terms of changing the induction regimen from twice a day, which is how we've tested it in the phase2a/2b into once a day for the first 3 weeks in the phase 3. We also looked at localized skin reactions and whether that was dose related and in fact found a couple of things, there was really no dose relationship between skin reactions and dose. And more importantly, the vast majority of skin reactions that happen, happen really in the first 2 to 4 weeks. And after 2 to 4 weeks, they tend to resolve, which again, supports our current induction regimen in the phase 3 program which is currently underway.
What we add to the science, both of this meeting and previous meetings is the fact that from a genotype standpoint, and a phenotype standpoint, really doesn't matter if you have x-linked or lamellar disease. In both populations, the Delta, the difference between drug response and vehicle, is identical regardless of which genotype you have. We also show that pediatric and adult patients based on age above and below 18, response rates are nearly identical. What was new at this meeting that we showed was the fact that it's well known with retinoids that they can affect serum concentrations of liver function studies, cholesterol, platelets, white blood cells, and red blood cells. And what we found in this trial was 0.05% dose had no effect at all on hepatic toxicity or causing hepatic toxicity, no evidence of changing cholesterol, no evidence of changing platelets, which again indirectly indicates that we have minimal absorption of the drug, which is exactly what you would want to have with a topical isotretinoin product is basically all of the drugs staying in the skin, where the disease is, and very little getting into the systemic circulation.
The other thing we found that's probably very important, not just to us, but to the entire ichthyosis community and other companies, is the fact that the currently utilized quality of life questionnaires such as the Dermatology Life Quality Index, or the children's DLQI, though patients will report that they have quality life issues, when you actually look at their scores, the vast majority, well over 80% or 85% of patients using these particular questionnaires, say they have no or minimal quality of life issues, even though 90% of their body may be covered by these scales. What we did find, however, is that patients who had significant quality of life inhibition showed a marked significant improvement in their quality of life. And so we're using a different quality of life questionnaire in our phase 3 program, which I think is important for the community to understand. We're very excited about the phase 3 program. It's currently underway in the United States and will shortly open hopefully, in Canada and in 3 European countries. We are very excited about the future. We're very excited about being able to bring a treatment to a disease that has an unmet need. And as always, I thank from the bottom of my heart, all of the subjects, the patients who have enrolled and will hopefully enroll in this trial and all of the investigators that have helped us to get to this point. Thank you for your time.