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, severe, genetic disorders characterised 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 (DEB) and junctional (JEB) EB in the 24-months open-label phase (OLP) of the EASE study.

Methods: EASE was a double-blind, randomised, 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 EB partial thickness wounds. OLP endpoints included: incidence, severity/relatedness of adverse events (AEs), wound infection maximum 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 Oleogel-S10 target wound treatment adherence was >99% and mean treatment duration was 584.7 days (±246.1 days). 71.7% 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. Severe and serious AEs were observed 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 attributable to treatment. Incidence of target wound infections was low (n = 7); five were mild-to-moderate and two 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 < 0.0001; -5.9% (8.6), P < 0.0001; -3.7% (9.0), P = 0.0026, respectively. Similarly, significant changes in EBDASI skin activity score from DBP baseline were observed: -3.9 (8.3), P < 0.0001; -5.1 (8.2), P < 0.0001; -3.0 (8.3), P = 0.0068, 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.