Long-term safety and efficacy of Oleogel-S10 (birch bark extract) in epidermolysis bullosa: 24-month results from the phase III EASE study

Background Epidermolysis bullosa (EB) is a group of rare and severe genetic disorders characterized by persistent skin fragility and open wounds. EB manifests as cutaneous and mucosal blistering, erosions and impaired wound healing. Objectives To determine the long-term efficacy, tolerability and safety of Oleogel-S10 (birch bark extract) in dystrophic EB (DEB) and junctional EB (JEB) in the 24-month open-label phase (OLP) of the EASE study. Methods EASE was a double-blind randomized controlled phase III study consisting of two phases: a 90-day double-blind phase (DBP) and a 24-month OLP. Patients from both former treatment groups in the DBP entered the single-arm OLP (n=205). Patients received Oleogel-S10 on all partial-thickness EB wounds. OLP endpoints included the incidence and severity/relatedness of adverse events (AEs), maximum wound infection severity, changes in body surface area percentage (BSAP) of wounds, EB Disease Activity and Scarring Index (EBDASI), pain, itch, disease severity and quality-of-life outcomes. Results The OLP data demonstrated that Oleogel-S10 target wound treatment adherence was > 99% and mean (SD) treatment duration was 584.7 (246.1 days). Seventy-two per cent of patients in the OLP were aged < 18 years and 86.8% had DEB; recessive DEB predominated (78.0%). AEs were reported in 77.1% of patients and were typically mild-to-moderate in severity. Severe and serious AEs were seen in 18.0% and 24.4% of patients, respectively. AEs resulted in the withdrawal of 7.8% of patients (n=16), including three with treatment-related AEs. Nine deaths were reported; none were attributable to the treatment. The incidence of target wound infections was low (n=7); five were mild-to-moderate in severity and two were severe. In patients treated with Oleogel-S10 throughout, mean (SD) BSAP changes from DBP baseline at 3, 12 and 24 months were −4.3% (8.1) (P<0.001), −5.9% (8.6) (P<0.001) and −3.7% (9.0) (P=0.003), respectively. Similarly, significant changes in EBDASI skin activity score from DBP baseline were observed: −3.9 (8.3) (P<0.001), −5.1 (8.2) (P<0.001) and −3.0 (8.3) (P=0.007) at 3, 12 and 24 months, respectively. Conclusions These data support an encouraging long-term safety profile of Oleogel-S10 and a sustained reduction in wound burden over at least 24 months of Oleogel-S10 treatment.