Biofrontera Inc., a biopharmaceutical company specializing in the commercialization of dermatologic products, today announced that the U.S. Food and Drug Administration (FDA) has issued a "no filing review issues identified" letter regarding the sNDA (supplementary New Drug Application) submitted by its licensor Biofrontera Bioscience GmbH to increase the maximally approved dosage from one to three tubes of Ameluz® per treatment. FDA has completed its filing review and will begin its substantive review of Biofrontera's communication.
AMELUZ® (aminolevulinic acid hydrochloride) topical gel, 10%, a porphyrin precursor, in combination with photodynamic therapy using BF-RhodoLED® lamp, is indicated for the lesion-directed and field-directed treatment of actinic keratoses of mild-to-moderate severity on the face and scalp.
Actinic keratosis (AK) is the most common pre-cancerous skin lesion caused by chronic sun exposure that may, if left untreated, develop into life-threatening skin cancer called squamous cell carcinoma. AKs typically appear on sun-exposed areas such as the face, bald scalp, arms or the back of the hands. In 2020 approximately 58 million people in the US were affected by AK, according to the Skin Cancer Foundation and 13 million AK treatments were performed.
"The studies supporting this application showed robust safety parameters for the simultaneous use of three tubes, with systemic and application site adverse events equivalent to those with one tube," says Hermann Luebbert, Chief Executive Officer and Chairman of Biofrontera Inc. "Many patients have actinic keratoses over large surface areas and the ability to treat these pre-cancerous lesions in one office visit is more convenient for patients and more efficient for their dermatologists."
The sNDA is supported by two clinical phase I studies investigating the safety of the application of three tubes of Ameluz®. The first study investigated the blood levels of 5-aminolevulinic acid, the active ingredient in Ameluz®, and its active metabolite protoporphyrine IX (PpIX), in 32 patients. Blood concentrations of these compounds were determined at 14 time points before and up to 10 hours after treatment in two groups of patients: 16 receiving photodynamic therapy (PDT) and three tubes of Ameluz on the face or scalp, and 16 receiving PDT and 3 tubes of Ameluz on other parts of the body. Further to a Type A meeting with the FDA in 2021, an additional safety trial with 100 patients receiving PDT with three tubes of Ameluz® was conducted. This data also formed part of the sNDA.
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The studies showed that after application of three tubes the blood concentrations of the active ingredient and the metabolite are transiently increased but they were several magnitudes below those at which side effects are known to occur. The systemic and application site adverse events were similar to those observed with one tube of Ameluz®, with patients frequently experiencing a transient inflammatory response at the application site and pain during illumination that was managed by a cooling air stream.