Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study

Abstract

Background Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death. Objectives EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited. Methods Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and < 9 months that was 10–50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel – both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of patients with first complete closure of target wound within 45 days. Results A total of 223 patients were enrolled and treated (109 treated with Oleogel-S10, 114 with control gel). The primary endpoint was met; Oleogel-S10 resulted in 41·3% of patients with first complete target wound closure within 45 days, compared with 28·9% in the control gel arm (relative risk 1·44, 95% confidence interval (CI) 1·01–2·05; P = 0·013). Adverse events (AEs) occurred with similar frequency for Oleogel-S10 (81·7%) compared with control gel (80·7%). AEs were predominantly of mild-to-moderate intensity (4·6% were severe). Conclusions Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB. Oleogel-S10 was well ­tolerated.

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023

“…Research has revealed that the application of topical birch triterpenes enhances wound healing within 45 days. Importantly, the incidence of AE, including infections, was found to be similar to that observed with control gel treatment (Kern et al 2023 ). The FDA granted birch triterpenes orphan drug, fast track, and priority review designations.…”

Mapping the burden of severe forms of epidermolysis bullosa – Implications for patient management

“…For example, results of a recent phase 3 trial in patients with severe forms of EB found that the topical gel Oleogel-S10 (birch bark extract, also referred to as birch triterpenes) demonstrated accelerated wound healing by achieving complete target wound closure in 41.3% of target wounds compared to 28.9% with vehicle control gel ( P = .013) within 45 days. 16 This accelerated wound healing with Oleogel-S10 resulted in a reduction in total body wound burden. 16 , 17 On the basis of these results, Oleogel-S10 (birch bark extract) has now been approved for treatment of partial thickness wounds associated with JEB and DEB in the EU and UK.…”

“… 16 This accelerated wound healing with Oleogel-S10 resulted in a reduction in total body wound burden. 16 , 17 On the basis of these results, Oleogel-S10 (birch bark extract) has now been approved for treatment of partial thickness wounds associated with JEB and DEB in the EU and UK. Another recent publication reporting the phase 3 trial evaluating the redosable topical gene therapy beremagene geperpavec, in patients with DEB reported complete wound healing occurred in 67% of the wounds exposed to beremagene geperpavec as compared with 22% of those exposed to placebo ( P = .002).…”

“Quality of Life in Epidermolysis Bullosa” and “Epidermolysis Bullosa Burden of Disease”: Italian translation, cultural adaptation, and pilot testing of two disease-specific questionnaires

“…Of note, the rst two treatments for EB skin wounds have been recently approved by regulatory agencies. The rst one, Oleogel-S10, is a gel containing triterpenes extracted from birch bark that proved effective and safe in accelerating healing of EB wounds and reducing pain [33]. Oleogel-S10 has been approved by the European Medicine Agency (EMA) and the Food and Drug Administration (FDA) for use in DEB and JEB patients aged > 6 months.…”