Oral Presentation Australasian Society for Dermatological Research Annual Scientific Meeting 2017

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2 randomised, placebo-controlled, double-blind clinical trial (#27)

Johann W. Bauer 1 , Alain Hovnanian 2 3 4 , Juliette Ly 2 3 4 , Hana Buckova 5 , Victoria Brunner 1 , Thomas Lettner 1 , Michael Ablinger 1 , Thomas Felder 6 , Peter Hofbauer 7 , Martin Wolkersdorfer 7 , Florian B. Lagler 8 , Wolfgang Hitzl 9 , Anja Diem 1 , Sophie Kitzmüller 1 , Greg Licholai 10 , Verena Wally 1
  1. Division of Experimental Dermatology and EB House Austria, Department of Dermatology, Paracelsus Medical University, Salzburg, Austria
  2. INSERM UMR 1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France
  3. University Paris Descartes - Sorbonne Paris Cité, Paris, France
  4. Department of Genetics, Necker Hospital, Paris, France
  5. Department of Pediatric Dermatology, Children´s Hospital, University Hospital Brno, Brno, Czech Republic
  6. Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
  7. Department of Production, Hospital Pharmacy, Salzburg, Austria
  8. Institute for Inborn Errors of Metabolism and Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria
  9. Paracelsus Medical University, Research Office, Biostatistics, Salzburg, Austria
  10. Chief Scientific Officer and President, Castle Creek Pharmaceuticals LLC, Parsippany, NJ, USA

Objectives: Clinically meaningful treatment of EBS requires significant and sustainable reduction of blister formation. Currently, there is no treatment for this rare condition.

Materials & Methods: We conducted a randomized, controlled, Phase 2/3 trial of topical application of 1% diacerein cream in 17 EBS patients. A 4-week intervention phase (primary end point: reduction in blister numbers >40%) and a 3-month follow-up were conducted in 2 sequential years, with a cross-over of groups after year 1. Reaching initial blister numbers (+/-10%) was a secondary end point. Pharmacokinetic analysis of rhein was performed in 2 patients.

Results: 60% of discerein patients and 15% of placebo patients had a reduction in blister numbers >40% after 4 weeks of intervention. At the 3-month follow-up, 12.5% of diacerein patients and 67% of placebo patients reached baseline blister numbers. The highest level of rhein in urine and serum was 39.9 ng/mL and 20.1 ng/mL, respectively, which is at least 100 times lower than the level after oral adminstration. No adverse effects were observed.

Conclusions: This trial provides evidence that the orphan drug diacerein 1% cream is highly efficacious and may provide a sustainable long-term effect on blister formation in EBS patients.

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