The U.S. Food and Drug Administration (FDA) has issued a “no filing review issues identified” letter regarding Biofrontera’s sNDA (supplementary New Drug Application) which aims to increase the maximally approved dosage from one to three tubes of Ameluz per treatment.
The FDA has completed its filing review and will begin its substantive review of Biofrontera’s communication with a target action date of October 4, 2024.
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.
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.
“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, in a news release. “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. Therefore, we believe this approval, if granted, will lead to increased use of Ameluz in the US.”
