Medical Education Library

A New Treatment Option for Epidermolysis Bullosa Simplex

An Interview with Dr. Amy Paller


Amy Paller, MD
Walter J. Hamlin Professor and Chair, Department of Dermatology, and Professor of Pediatrics
Director, Northwestern University Skin Disease Research Center (SDRC)
Northwestern University Feinberg School of Medicine
Chicago, Illinois

Dr. Paller reports that she has received an honorarium for consultation for Castle Creek Pharmaceuticals LLC. She also reports that she is an investigator for a diacerein trial.

What is EBS and what is the DELIVERS Study?

DR. AMY PALLER: Epidermolysis bullosa simplex (EBS) is the most common type of epidermolysis bullosa, which is a genetic blistering disorder that can start early in childhood, or sometimes be present at birth. EBS is particularly difficult during the first decade of life, with extensive blistering and great discomfort.

DELIVERS is an ongoing multicenter, randomized, double-blind, parallel-group phase 2 study evaluating the safety and efficacy of diacerein 1% ointment. In this study, patients are randomized to either the active treatment with the diacerein 1% or its vehicle ointment. Patients apply the ointment once a day for 8 weeks with follow up that can be as long as 20 weeks.

Patient-reported outcomes are being assessed include blistering, itch, pain, and decreased mobility, all of which affect the patient's quality of life.

How many centers are currently recruiting patients and who can qualify?

The DELIVERS study has been open since June of 2017 and the study is currently being conducted in 20 sites throughout the United States and Europe, Israel, and Australia, so it's truly international. It is enrolling patients who have a documented genetic mutation consistent with any form of EBS with at least 2% body involvement (that documentation is done as part of the study). Patients must be at least 4 years of age.

In addition, we are conducting another study to better understand the safety and absorption of diacerein 1% ointment under maximum use conditions.

What exactly is a pharmacokinetic (PK) study and why is it needed for regulatory approval?

DR. AMY PALLER: With any new drug it's important to determine systemic absorption and how long the medication stays in the circulation. This is particularly important in EBS because of the blistering and reduced epidermal barrier. And the greater the extent of skin blistering, the greater the chance of systemic exposure through their use of higher doses and frequency of application. The FDA wants a better understanding of plasma concentrations in this subset of patients, which is valuable by helping establish dosing recommendations or identifying potential systemic adverse effects. A maximal use PK study is conducted to increase the systemic exposure through the use of higher concentration, frequency of dose, or greater body surface area involvement under controlled conditions.

Are there any blood draws and how many patient visits are needed for this study?

DR. AMY PALLER: The PK study is being conducted at 8 locations in the United States and Europe, where patients are applying 1% diacerein for 10 days (active medication only). There are 2 patient visits (Day 1 and Day 10) with a series of blood draws at each of those visits. Patients have a preapplication draw, and then a series of subsequent draws: a half hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and 8 hours. This is so we can look at what is getting into the bloodstream in that period of time after the daily application.

Are there additional benefits for patients participating in these studies?

DR. AMY PALLER: First, there's the potential benefit of improvement. This is a medication that targets interleukin 1 beta, which has been shown to be increased in the disease. Also, the sponsor will cover all expenses for eligible patients participating and, once patients have successfully completed the study, they will also receive free medication for up to 2 additional treatment cycles totaling 8 months. Patients that complete the double-blind DELIVERS study or participate in the open-label PK study may be eligible to enter an open-label extension study.

This interview was produced by the Custom Programs division of Frontline Medical Communications. The editorial staff of Pediatric News and Dermatology News was not involved in the content development.

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