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FDA To Permit Using 3 Tubes of Actinic Keratosis Drug Per Treatment


An increased number of tubes of aminolevulinic acid hydrochloride 10% will help patients who have actinic keratosis over large surface areas.



Biofrontera on Monday announced that the US Food and Drug Administration (FDA) had issued a "no filing review issues identified" letter regarding the maximally approved dosage of its AK drug aminolevulinic acid hydrochloride 10% (Ameluz).

The letter was in response to the company’s supplementary new drug application to increase dosage from 1 to 3 2-g tubes of the topical gel per treatment.

The topical gel has been indicated for the lesion-directed and field-directed treatment of actinic keratoses of mild to moderate severity on the face and scalp. It is to be used in a clinical setting in combination with photodynamic therapy (PDT) using the BF-RhodoLED lamp.1

The FDA has completed its filing review and will begin its substantive review of Biofrontera's communication, the company reported. The FDA has set a target action date of October 4, 2024.

"The studies supporting this application showed robust safety parameters for the simultaneous use of 3 tubes, with systemic and application site adverse events equivalent to those with 1 tube," said Hermann Luebbert, chief executive officer and chairman of Biofrontera, in a news release.2

"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," he said.

The sNDA is supported by 2 clinical phase I studies investigating the safety of the application of 3 tubes of aminolevulinic acid hydrochloride 10%, according to the company. The first study investigated the blood levels of 5-aminolevulinic acid, the active ingredient in aminolevulinic acid hydrochloride 10%, 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 2 groups of patients: 16 receiving PDT and 3 tubes of aminolevulinic acid hydrochloride 10% on the face or scalp, and 16 receiving PDT and 3 tubes of aminolevulinic acid hydrochloride 10% 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 3 tubes of aminolevulinic acid hydrochloride 10% was conducted. This data also formed part of the supplementary new drug application, Biofrontera reported.

The studies showed that after application of 3 tubes, the blood concentrations of the active ingredient and the metabolite were 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 the use of 1 tube of ofaminolevulinic acid hydrochloride 10%, with patients frequently experiencing a transient inflammatory response at the application site and pain during illumination that was managed by a cooling air stream, according to the company.


  1. Petronelli M. Biofrontera seeks FDA-approval of BF-RhodoLED XL for AK. Dermatology Times. March 31, 2021. Accessed February 7, 2024. https://www.dermatologytimes.com/view/biofrontera-seeks-fda-approval-of-bf-rhodoled-xl-for-combo-treatment-of-ak
  2. Biofrontera Inc. Announces FDA filing of supplemental new drug application for ameluz(r) to permit up to three tubes per use. News release. February 5, 2024. Accessed February 7, 2024. https://finance.yahoo.com/news/biofrontera-inc-announces-fda-filing-221500957.html
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