First-Ever Positive Phase III Trial in Epidermolysis Bullosa

A topical treatment derived from tree bark significantly increased healing of epidermolysis bullosa (EB) lesions versus standard care in an international multicenter clinical trial.

After 45 days of treatment, 41.3% of patients randomized to oleogel-S10 (Filsuvez) had complete wound closure as compared with 28.9% of the control group. A subgroup analysis showed that the beneficial effects were limited to patients with recessive dystrophic, which accounted for almost 80% of the study population.

The wound-healing advantage of oleogel-S10 emerged at about 30 days and persisted out to 90 days, when the proportion of patients with healing became similar in the two treatment groups, reported Dedee Murrell, MD, of the University of New South Wales in Kensington, Australia, during the European Academy of Dermatology and Venereology virtual conference.

“The time to event, which is wound healing over 90 days … was not statistically significant overall,” she said. “The wound healing trajectories demonstrated that oleogel-S10 accelerates wound healing in a subset of the wounds. However, as expected, with good wound care, the control group begins to catch up later by 90 days. The difference in the proportion of healed target wounds had narrowed between treatment groups at 90 days, but the control group never overtook the oleogel arm.”

“This is the first time that a phase III trial in EB has met its primary endpoint,” she added.

Background of Development

A rare genetic skin-fragility disorder, EB characteristically emerges as a pattern of recurring healing and break-down wounds, along with chronic slow-healing or nonhealing wounds. The condition has no approved therapy, and standard of care consists of nonadhesive bandages, topical antimicrobial agents, topical steroids, and various unapproved therapies that are not specific for EB, Murrell noted.

The primary active ingredient in oleogel-S10 is betulin, a naturally occurring triterpene found in the bark of certain types of birch trees. Dry betulin extract is mixed with sunflower oil to form a gel, which is applied directly to EB lesions and to the contact surface of bandages. The mechanistic rationale for its use in EB includes evidence that triterpenes help modulate inflammation and are involved in keratinocyte proliferation, migration, and differentiation.

Preliminary clinical research provided evidence of accelerated wound healing in patients with dystrophic EB. The work subsequently led to the international phase III EASE trial. Investigators at 58 sites in 28 countries enrolled 223 patients, primarily with dystrophic EB but also junctional EB or Kindler syndrome. Eligible patients had a partial thickness wound 10-50 cm2 in size, persisting for 21 days to 9 months.

Patients were randomized to oleogel-S10 or control gel, each in addition to standard dressings changed at least once every 4 days. The primary endpoint was the proportion of patients who had a first complete closure of a target wound within 45 days. Secondary endpoints included time to wound healing, proportion of target wounds healed within 90 days, incidence and severity of wound infections, change in total body wound burden, change in itching, and adverse events.

Patients ages 4-12 years accounted for

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