Sirolimus and EB simplex
Dr. Murrell noted that a pilot study, known as the SISTERS trial, had been conducted with a 2% sirolimus topical ointment at her institution and at Stanford (Calif.) University. This prospective, double-blind study had involved 16 patients with EB simplex, in which blisters tend to be confined to the palms of the hands and soles of the feet. The patients were assigned to treat both feet with either topical sirolimus or a placebo cream for 12 weeks. After a 4-week wash-out period, the patients switched to using the opposite cream for an additional 12 weeks.
Sirolimus is an inhibitor of the mTOR pathway, and, according to a description of the study on ClinicalTrials.gov, the researchers’ aim was to inhibit “the mTOR pathway to down-regulate the translation of defective keratin proteins.” That would allow a transition from supportive care, which is the current practice for EB simplex, to using a targeted molecular therapy to improve patient mobility and quality of life, they note on the site.
“We look forward to having that study unblinded,” Dr. Murrell said, adding that “data should be ready in a few months.”
EASE and Oleogel-S10
Oleogel-S10 is a gel that contains a birch bark extract dissolved in sunflower oil. It is already approved in Europe (Episalvan) for the treatment of partial-thickness skin wounds, but its use in EB remains investigational.
In a poster presentation at the meeting, Stella Gewert, MD, of the University of Freiburg (Germany) and colleagues discussed their experience using Oleogel-S10 in the treatment of four patients – each with a different type of EB – who applied the gel for between 6 days and 3 months.
Promising effects were seen, including reduced pruritus and pain, wounds healing more quickly, and reductions in lesion size. “During treatment, dressing requirements were reduced, and patient quality of life improved,” the researchers observed.
Mark Sumeray, MD, the chief medical officer of Amryt Pharmaceuticals, which is developing Oleogel-S10, said it was important to emphasize that Oleogel-S10 is a gel and not a cream. Gels are mixed with oil and are easier to apply – an important consideration for those with EB, he explained, whereas creams tend to be mixed with water and are stickier.
The phase 3 EASE trial is looking at the efficacy and safety of the gel in patients with junctional and dystrophic EB, and recruitment is ongoing, Dr. Murrell said. The primary endpoint is the proportion of patients with the first complete closure of a target wound within 45 days of treatment initiation. The estimated primary completion date for the trial is June 2020, and it is projected to end by 2022.
Scioderm, in collaboration with Amicus, funded the ESSENCE trial; Castle Creek financed the DELIVERS study; Amryt is supporting the EASE study; and Stanford University is sponsor of the SISTERS study. Dr. Murrell has been the principal investigator for trials run by Amicus, Amryt, Castle Creek, and Shire, and she acknowledged receipt of honoraria or consultation fees from those companies and others. Dr. Gewert did not report any financial disclosures. Dr. Sumeray is an employee and shareholder of Amryt.