By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The U.S. Food and Drug Administration (FDA) has approved a treatment for wounds associated with junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB) not specific to a particular mutation. Birch triterpene is a botanical drug substance composed of a mixture of pentacyclic triterpenes (e.g., botulin, lupeol, betulinic acid, erythrodiol, and oleanolic acid) formulated as a topical gel.1 It was given a priority review and orphan designation and is distributed by the Chiesi Group as Filsuvez.
INDICATIONS
Birch triterpenes topical gel is indicated for the treatment of wounds associated with DEB and JEB in adults and pediatric patients 6 months of age and older.1
DOSAGE
The recommended dose is to apply a 1 mm layer of gel to the affected wound surface and cover with wound dressing or apply directly to dressing so that the gel is in direct contact with the wound.1 The gel should not be rubbed in. Application should continue until the wound is healed. Birch triterpenes (10%) is available as a one-time use in 25 mL sterile tubes.
POTENTIAL ADVANTAGES
Birch triterpene gel is FDA-approved treatment for JEB and DEB with clinical activity for re-epithelialization and accelerated healing in partial thickness wounds.1-3 It is an alternative to beremagene geperpavec-svdt (Vyjuvek), topical gene therapy for those specifically with mutation in the collagen type VII alpha1 chain (COL7A1) gene.4
POTENTIAL DISADVANTAGES
Birch triterpene gel may be less effective in patients with certain EB subtypes (dominant EB [DDEB] and JEB).1-3
COMMENTS
Birch triterpene is a botanical substance obtained from the bark of two types of birch trees native to Europe. The efficacy of birch triterpenes was evaluated in a randomized, double-blind, vehicle-controlled trial in subjects with DEB and JEB.1,3 The median age was 13.0 years, 62.4% were male, and 83.5% had recessive DEB (RDEB). Subjects were randomized to birch triterpene (n = 109) or control gel (n = 114). The primary endpoint was the proportion of subjects with investigator assessment of the first complete closure of the target wound by day 45 of the 90-day, double-blind phase of the study. Response rates were 41.3% vs. 28.9% overall. Rates were 44.0% vs. 26.2% for RDEB (n = 175), 50% vs. 50% for DDEB (n = 20), and 18.2% vs. 26.7% for JEB (n = 26). Those randomized to birch triterpenes had one less dressing change every two weeks at day 90.3
CLINICAL IMPLICATIONS
Epidermolysis is a rare genetic skin disease primarily affecting pediatric patients.4 It is characterized by mechanical fragility of epithelia surface leading to defective attachment between and within the epidermis and dermis of the skin. This can result from a mutation in any of at least 18 genes encoding the proteins in the epidermis, basement membrane, or dermis.4 This typically leads to blistering, erosion, and ulceration of the skin and mucosa that can be trigger by minor trauma or friction. Repeated blistering and fibrosis can lead to squamous cell carcinoma and life-threatening infections. RDEB typically is more generalized and severe than DDEB.4 JEB is caused by autosomal recessive mutations in the lamini-332 genes plectin and a6b4 integrin.4 DEB is caused by either recessive or dominant mutation in COL7A1. There currently is no cure. The condition is managed by supportive care including daily wound care, bandaging, and pain management as needed.4 Birch triterpenes provides an alternative to this rare condition. Beremagene geperpavec-svdt, an HSV-1-based gene therapy, is specific for COL7A1 mutations and has shown about 67% complete healing vs. 22% for placebo gel at six months.5,6 The cost for Filsuvez was not available at the time of this review.
REFERENCES
- Filsuvez prescribing information. Chiesi Group. https://resources.chiesiusa.com/Filsuvez/FILSUVEZ_PI.pdf
- Center for Drug Evaluation and Research. Application number 215064Orig1s000. Multi-discipline review. Filsuvez. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/215064Orig1s000MultidisciplineR.pdf
- Kern JS, Sprecher E, Fernandez MF, et al. Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: Results from the phase III randomized double-blind phase of the EASE study. Br J Dermatol 2023;188:12-21.
- National Organization for Rare Disorders (NORD). Rare disease database. Epidermolysis Bullosa. Last updated: Jan. 22, 2024. https://rarediseases.org/rare-diseases/epidermolysis-bullosa/
- Vyjuvek prescribing information. Krystal Biotech, Inc. May 2023. https://www.fda.gov/media/168350/download
- Guide SV, Gonzalez ME, Bagci IS, et al. Trial of beremagene geperpavec (B-VEC) for dystrophic epidermolysis bullosa. N Engl J Med 2022;387:2211-2219.
