Diacerein for the treatment of epidermolysis bullosa simplex

Short lay summary

Currently, there is no effective therapy available for EB and treatments focus on pain management and wound care. First gene therapeutic approaches are currently under investigation, however, these are not applicable for all types of EB. Our aim was to develop a therapy applicable for patients suffering from the “simplex” type of EB (EBS), which is triggered by gene mutations within either the keratin 5 or 14 gene. While both genes are still translated into protein, these form clumps and trigger an inflammatory cascade, resulting in severe skin blistering. We used the small molecule diacerein in a clinical trial on 17 patients. Children from 4 to 18 years were included and blister numbers were reduced on average by 87%. The positive results of this trial facilitated the uptake of this project by Castle Creek Pharmaceuticals, who will pursue the clinical development of this cream, in order to achieve marketing authorization.

Scientific summary

We conducted a randomized-controlled phase 2/3 clinical trial of topical diacerein in a 1% formulation with Ultraphil, to treat defined skin areas of EBS-gen sev patients. 17 patients were randomly assigned to receive either 1% diacerein cream or placebo. Skin areas were defined as 3% of the body surface area, with the pre-requisite of blisters present at the beginning of the treatment period. These areas were treated once daily.

Efficacy was evaluated based on an evaluation of responders, defined as showing a reduction of blister numbers of at least 40% after the intervention phase, which is a clinically meaningful reduction. According to this definition, in the diacerein group, 60% of patients responded to the treatment, as opposed to only 15% of patients of the placebo group. Only 12.5% of patients reached at least 90% of initial blister numbers after the follow-up, as opposed to 67% of patients from the placebo group.

This trial provides evidence for the efficacy and tolerability of the 1% diacerein cream in generalized-severe EBS. Further, this is the first targeted, small molecule-based treatment for EBS, therefore baring high potential for patient care. Interestingly, a long-term effect of the treatment was observed, as only 12.5% of all patients from the diacerein group regained initial blister numbers even 8 weeks after stopping the treatment.

Strategic relevance

• DEBRA strategic goal: ‘Develop disease-modifying and curative therapies’ through research and clinical studies, to develop therapies that target the underlying disease mechanism in EB.
• Project goal: to develop a topical treatment for EBS patients, which significantly reduces blister numbers and increases the quality of life.
• Preceding/ follow-on projects, and related projects: This project builds on a pilot study supported by DEBRA Austria.