TMB-001 safety results show minimal systemic absorption of isotretinoin
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Key takeaways:
- There was minimal absorption of isotretinoin when TMB-001 0.05% was applied to 75% to 90% of the body.
- Full pharmacokinetic results will be presented at the Society for Pediatric Dermatology Annual Meeting.
In new pharmacokinetic analyses, patients treated with TMB-001 0.05% ointment for congenital ichthyosis experienced minimal systemic absorption of isotretinoin or its major metabolites, Timber Pharmaceuticals announced in a press release.
TMB-001 ointment is a topical formulation of 0.05% isotretinoin that has received both breakthrough therapy designation and fast track status from the FDA.
The interim pharmacokinetic (PK) results are from the phase 3 ASCEND study, an ongoing double-blind, vehicle-controlled, randomized 12-week study of TMB-001 0.05% ointment for the treatment of patients aged 6 years and older with congenital ichthyosis (CI).
Healio spoke with Alan Mendelsohn, MD, executive vice president and chief medical officer of Timber Pharmaceuticals, about the significance of these results.
“We are in fact achieving levels of success in patients with this topical with almost no drug levels in the blood,” he said.
The PK data were collected from the first nine patients who completed 15 days of the 12-week, open-label, maximal use study in the ASCEND program.
The results showed that when TMB-001 0.05% is applied to 75% to 90% of the body, there was minimal absorption of isotretinoin. By day 14 of treatment, mean plasma concentration of the nine subjects was 4.83 ng/mL (range, 1.46-16.59). Mean levels of 4-oxo-isotretinoin, tretinoin and 4-oxo-tretinoin were 13.71 ng/mL, 0.08 ng/mL and 0 ng/mL, respectively.
“Most of the side effects are either dose or serum concentration related,” Mendelsohn said. “So having a lower rate, like we will show, is an important factor, because we’re really not seeing any side effects beyond the ones that you might expect with topical retinoids in general.”
According to Mendelsohn, the ASCEND trial is the first to test the safety and efficacy of this ointment in children aged as young as 6 years, and results should be available “in the very near future, within the next 6 to 12 months.”
The current results are not only groundbreaking for the treatment of CI but could be monumental for other indications as well such as acne, according to Mendelsohn.
“We have potentially developed one of the safest forms of isotretinoin ... that will potentially get the same efficacy as oral isotretinoin, but without any of the baggage,” he said, alluding to iPledge, bone problems, lipid issues and many other guidelines and side effects that dermatologists need to manage when prescribing isotretinoin.
“If this can be developed for other diseases, it would be a breakthrough in retinoid therapy,” he said.
The company will present full PK results for the indication of CI at the Society for Pediatric Dermatology Annual Meeting to be held in July in Asheville, North Carolina.