FDA Approves 3 Tubes of Aminolevulinic Acid Hydrochloride for Actinic Keratosis

In an announcement by Biofrontera Inc., it was confirmed that the US Food and Drug Administration (FDA) approved the raising of the maximum dosage of aminolevulinic acid hydrochloride (Ameluz) for actinic keratosis from a single tube to 3 tubes for each treatment.¹

The decision by FDA officials follows the February letter issued by the agency indicating that there had not been any filing review issues found following Biofrontera’s submission of their supplemental New Drug Application (sNDA) for the raising of the treatment’s maximum dosage for those with actinic keratosis.² The condition is the most common pre-cancerous skin lesion and results from chronic sun exposure.

“Up to 60% of squamous cell carcinomas begin as untreated (actinic keratosis) lesions, so it’s important for us to be able to treat the entire affected field," Jonathan Weiss, MD, investigator and co-managing partner at Georgia Dermatology Partners in Atlanta, said in a statement. "I have used Ameluz now for more than 7 years for the management of (actinic keratosis) because of the demonstrated efficacy and safety it delivers. With the approval of the sNDA, I look forward to being able to use up to three tubes for those patients that need them."

Actinic keratosis can also develop into the life-threatening skin cancer known as squamous cell carcinoma, with keratoses typically appearing on sun-exposed regions on one’s body such as a bald scalp, the face, the arms, or the back of patients’ hands. There are approximately 58 million people in 2020 within the US who were impacted by actinic keratosis.

The skin condition is often taken less seriously than various other dermatologic conditions, despite the danger of developing skin cancer. Neal Bhatia, MD, director of clinical dermatology for Therapeutics Clinical Research and chief medical editor for Practical Dermatology, highlighted in a previous HCPLive interview the importance of timing for treatment.³

Aminolevulinic acid hydrochloride is used to treat patients in combination with photodynamic therapy for actinic keratoses. The sNDA for the dosage increase of aminolevulinic acid hydrochloride was supported by the results of two phase 1 studies looking into the safety of the 3 tubes of the treatment.²

One of these trials split subjects into 2 cohorts, with 1 cohort being given photodynamic therapy and 3 tubes of aminolevulinic acid hydrochloride on the face or scalp. The other cohort was treated on different parts of the body, and there were 32 total participants.

The investigators had examined the blood levels of 5-aminolevulinic acid and its active metabolite protoporphyrin IX (PpIX), looking at the results at several different time points for up to 10 hours following treatment. There had also been a safety trial assessing 100 subjects undergoing photodynamic therapy and given 3 tubes of aminolevulinic acid hydrochloride.

The findings resulting from these studies indicated that while the blood concentrations of the active ingredient and metabolite were indicated to have transiently grown after the application of 3 tubes, the investigators found that concentrations were far below levels associated with possible side effects.

In addition, any adverse events (AEs) at either the application site or those that were systemic, were comparable to AEs seen with utilization of only a single tube. Temporary inflammation and manageable levels of pain at the time of illumination were noted.

“We are delighted with the FDA’s decision to approve the use of up to three tubes of Ameluz per treatment,” Hermann Luebbert, Biofrontera's chief executive officer and chairman, said in a statement. “We are now working with Medicare and commercial payers to obtain reimbursement for this label update and will notify our customers accordingly.”

References

1. ^{FDA Approves Use of Up To Three Tubes of Biofrontera Inc.’s Ameluz (aminolevulinic acid HCI) Topical Gel, 10% In One Treatment. Biofrontera Inc. October 7, 2024. https://www.globenewswire.com/en/news-release/2024/10/07/2958931/0/en/FDA-Approves-Use-of-Up-To-Three-Tubes-of-Biofrontera-Inc-s-Ameluz-aminolevulinic-acid-HCI-Topical-Gel-10-In-One-Treatment.html.}
2. ^{Smith T. Biofrontera Files sNDA for Increased Dosage of Aminolevulinic Acid Hydrochloride for Actinic Keratosis. HCPLive. February 7, 2024. https://www.hcplive.com/view/fda-accepts-snda-to-increase-dosage-of-aminolevulinic-acid-hydrochloride-for-actinic-keratosis. Date accessed: October 4, 2024.}
3. ^{Smith T. Neal Bhatia, MD: Timing, Adherence, Unmet Needs Among Patients with Actinic Keratosis. HCPLive. January 19, 2024. https://www.hcplive.com/view/neal-bhatia-md-timing-adherence-unmet-needs-among-patients-with-actinic-keratosis. Date accessed: October 4, 2024.}