Birch extract approved by FDA for rare disease

A new topical medication based on a mixture of triterpenes found in birch trees has been FDA-approved for the care of patients with Epidermolysis Bullosa, a rare skin disease.

Filsuvez is a new FDA-approved drug for the treatment of EB. It is a mixture of triterpenes derived from an extract of birch bark.

Epidermolysis bullosa (EB) is a rare genetic disorder. Children born with EB have extremely fragile skin and blisters form on their skin, mucosal tissues, and internal linings of their organs. The underlying cause of the disease is a defect in how cellular layers of skin attach to each other. This occurs in ~20 out of 1 million live births in the United States and around half a million people live around the world have EB.

Unfortunately, there are no drugs that can currently cure this disease and the focus for patients is on wound care, protection of the skin, controlling infection, preventing additional trauma to the tissues, and managing pain and itch. The American Academy of Dermatology provides an overview of various forms of the disease, including images of patient presentations. I caution those not accustomed to images of complicated dermatologic conditions as these may be disturbing to see.

Depending upon the form and severity of EB, life-expectancy can be limited. This new botanical drug was approved for treatment of junctional and dystrophic EB, with junctional EB occurring in ~5% of all EB cases and dystrophic EB in ~25% of EB cases. Life expectancy for JEB patients is very poor, with nearly half dying in the first year of life. DEB patients have better early life expectancy, but are prone to developing a form of skin cancer (squamous cell carcinoma).

A new plant-derived drug offers some relief

A topical therapy, Filsuvez (birch triterpenes; also known by its development name as Oleogel-S10), was approved by the FDA in December 2023 for treatment of wounds in patients aged 6 months and older with junctional and dystrophic EB. It was previously approved for use in Europe and the UK. 

Composition of the drug

Filsuvez is classified as a ‘botanical drug’ by the FDA (the 4th such drug they have approved, following Veregen, Crofelemer, and NexoBrid). Unlike other botanically-derived small molecules developed into a drug (i.e., morphine, taxol, vincristine, etc.) the botanical drug category allows for mixtures of compounds found in a single plant ingredient. In the case of Filsuvez, this includes a mixture of triterpene molecules:

Major constituents found in the newly approved drug for EB.

This mixture of triterpenes has demonstrated antibacterial, antifungal, ant-inflammatory, and wound-healing properties in laboratory studies.

The description of the drug product in the FDA document is as follows:

FILSUVEZ (birch triterpenes) topical gel is a sterile botanical drug product for topical use and contains birch triterpenes in an oil base. FILSUVEZ is a colorless to slightly yellowish, opalescent, non-aqueous gel. Birch triterpenes is a botanical drug substance composed of a mixture of pentacyclic triterpenes. The botanical drug substance is a dry extract, refined, from birch bark from Betula pendula Roth, Betula pubescens Ehrh., as well as hybrids of both species, quantified to 72-88% (w/w) betulin, 2.4-5.7% (w/w) lupeol, 2.6-4.2% (w/w) betulinic acid, 0.5-1.2% (w/w) erythrodiol, 0.30.8% (w/w) oleanolic acid.

You’ll note that while this is a mixture of molecules, the FDA holds to a strict definition of the percentage ratios of these individual ‘marker compounds’ found in the mixture. The final formula contains 10% extract in a sunflower oil base for topical application to wounds.

Clinical findings

A phase III randomized double-blind phase of the EASE (Efficacy and safety of Oleogel-S10 in patients with EB) trial was undertaken to examine the efficacy and safety of the birch bark triterpenes (Oleogel S-10) compared to a control gel in sunflower vehicle. This was the largest phase III randomized controlled study in EB, enrolling 223 patients from 49 clinical sites in 26 countries (109 were treated with the Oleogel-S10 and 114 with the placebo control). A total of 199 patients completed the study. Major findings included:

• Improved wound closure in 45 days for patients using the Oleogel-S10 (41.3% in treatment group versus 28.9% in control group).

• Dressing changes are incredibly painful, and patients often need to be medicated to have their bandages changed. One major outcome was the need for one less dressing change every two weeks for those treated with Oleogel-S10 versus control gel.

• The Oleogel-S10 was well tolerated by patients.

Proportion of patients with first complete closure of epidermolysis bullosa (EB) target wound within day 45 (all patients and by EB subgroup). Source: Fig. 1 of EASE Study

The Takeaway

While this newly approved botanical drug does not cure EB, clinical findings show that it does offer some symptomatic relief in improvements in wound healing and reduction in the number of painful bandage changes required by patients. I am heartened to see this unique FDA-pathway being used to pursue the approval and delivery of multi-component chemistries found in plants to patients with difficult to treat conditions like EB.

Yours in health, Dr. Quave

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Cassandra L. Quave, Ph.D. is a Guggenheim Fellow, CNN Champion for Change, Fellow of the National Academy of Inventors, and award-winning author of The Plant Hunter. Her day job is as professor and herbarium curator at Emory University School of Medicine, where she leads a group of research scientists studying medicinal plants to find new life-saving drugs from nature. She hosts the Foodie Pharmacology podcast and writes the Nature’s Pharmacy newsletter to share the science behind natural medicines. To support her effort, consider a paid or founding subscription or donation to her lab research.

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