The Willingness to Participate in Genetic Studies may be Genetic

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ters on his skin since birth, developed conjunctival blisters at ages 4 and 6 years in the left and right eye, respectively, and underwent repeated superficial keratectomy and symblepharon lysis surgeries with amniotic membrane transplantation in his left eye. These procedures resulted in a temporary improvement in his visual acuity, but it returned to baseline in less than 3 months. Surgical symblepharon lysis of his right eye was performed, with subsequent weekly topical applications of B-VEC (5×109 PFU/mL) until the corneal epithelium was healed. This was followed by monthly topical applications. Prior to surgery, the patient had suffered from severe ankyloblepharon that reached the central cornea in both eyes. His visual acuity was hand motion in the right eye and 20/400 in the left eye. Four months post-surgery, the symblepharon had not recurred and the cornea had been completely re-epithelized. Visual acuity was 20/100. After 7 months and 24 doses of B-VEC, no abnormalities were observed in the retina, and B-VEC treatment was being scheduled for his left eye. “We did not find any adverse effects associated with ocular use,” Dr. Sabater reports. He adds that no other ocular cases have been treated with B-VEC. Phase 3 Findings The FDA based its approval on findings from a phase 3 randomized clinical trial that evaluated the safety and effectiveness of B-VEC in 31 patients (median age 16 years) with DEB, 30 of whom have RDEB. In an earlier paper, repeated topical application of B-VEC had resulted in fulllength, COL7A1 protein expression and normalized anchoring fibril formation, providing the basis for the phase 3 trial. A primary wound was selected for each patient, and wounds were matched according to size, region, and appearance. The wounds within each pair were randomly assigned for treatment with a weekly application of either B-VEC or placebo for 26 weeks. At 6 months, complete wound healing was observed in 67% of the wounds treated with B-VEC as compared with 22% of those exposed to placebo. Complete wound healing at 3 months occurred in 71% of subjects treated with B-VEC versus 20% in the placebo group. “We showed durable wound healing, and it really is a corrective therapy,” says study author Peter Marinkovich, MD, Associate Professor of Dermatology at Stanford University School of Medicine in Northern California. “The patient who received ocular therapy also was a participant in our trial and received B-VEC for his cutaneous wounds as well as ocular conditions—and he had very good results with his skin.” He also went from blind to almost normal vision, Dr. Marinkovich says. “His right eye went from seeing hand motion prior to the interventions to 20/40 vision 7 months post-surgery and after 24 doses of B-VEC.” For now, B-VEC is only approved for wound healing, but as it is now an approved drug, physicians will be able to use it off-label for ocular indications, reports Dr. Marinkovich. He adds, “We are also looking to see how the gel works on mucosal surfaces, including the mouth, throat, eyes, esophagus, and anus.”