295 Collagen 7 (C7) protein replacement therapy (PTR-01) durably reduces wound size and symptoms in patients with recessive dystrophic epidermolysis bullosa (RDEB)

Abstract

We treated 6 patients (13-30 yrs of age) with confirmed RDEB in a multicenter, open-label Phase 2 study. PTR-01 3.0 mg/kg IV was given weekly x4, then every other week x7 with follow up assessments 1 and 3 months after treatment. Response was defined as improvement of ≥2 points on a 7-point wound impression scale (WIS) in a majority of lesions. Multiple secondary outcomes and safety were assessed. Five patients completed the study, 4 of whom were considered responders on the WIS. Over 75% of lesions (both chronic and recurrent) were closed by 50% or more at the end of treatment and remained so for at least 1 month after treatment. Wound surface area over time indexed to baseline (AUCi) showed a median decline of 46% at Day 43 of treatment in comparison to 25% in a control group and declined further to 70% at the end of treatment. Surveys of EB symptoms, impact, and patient and investigator global impressions, which comprised both cutaneous and systemic manifestations, showed rapid and persistent improvements during treatment. NC2 staining of skin biopsies showed extensive basement membrane incorporation of PTR-01 though no increase in anchoring fibrils by immunoelectron microscopy. Elevated skin fibrosis markers were markedly reduced. There were no serious or unexpected adverse events. One patient withdrew at Day 50 for lack of efficacy in association with high anti-C7 antibodies. Treatment with PTR-01 resulted in durable effects on both cutaneous and systemic manifestations of RDEB and reduced fibrosis markers in a majority of patients.