sNDA for Aminolevulinic Acid Gel Plus PDT in sBCC Is Submitted to the FDA

A supplemental new drug application (sNDA) seeking the approval of red light photodynamic therapy (PDT) in combination with aminolevulinic acid gel (Ameluz) for the treatment of patients with superficial basal cell carcinoma (sBCC) has been submitted to the FDA.1 The filing is looking to expand the label of aminolevulinic acid gel to include the treatment of patients with sBCC using PDT with BF-RhodoLED or RhodoLED XL red light lamps.

The sNDA is supported by data from a phase 3 trial (NCT03573401), as well as data from an integrated safety assessment combining data from Biofrontera’s US and European BCC clinical studies. Findings from the phase 3 trial published in the Journal of the American Academy of Dermatology demonstrated that patients treated with PDT plus aminolevulinic acid gel (n = 145) achieved a 12-week composite clinical and histological clearance rate of 65.5% compared with 4.8% among patients who received placebo plus PDT (n = 42; P < .0001).2

“We are delighted that these highly significant results align with those found in the European studies and that we were able to submit this data package to FDA and seek an extension of the label to include sBCC,” Hermann Luebbert, PhD, chief executive officer and chairman of Biofrontera Inc. stated in a news release.1 “If approved, this would expand the [aminolevulinic acid gel] indication to cutaneous oncology and would represent a significant milestone in our mission to become market leaders in the field of PDT.”

What was the design of the phase 3 study of aminolevulinic acid gel in sBCC?

The randomized, double-blind, pivotal study enrolled adult patients with sBCC across 21 centers in the US.2 Patients needed to have at least 1 naive histologically confirmed lesion with a minimum diameter of 0.6 cm on the face, scalp, neck/trunk, and/or extremities; the treatment field was limited to approximately 20 cm2. Those with Gorlin syndrome, xeroderma pigmentosum, photodermatoses, porphyria, hypersensitivity to porphyrins or any ingredient of the aminolevulinic acid gel, or significant medical conditions potentially impairing study procedures or interpretation of data were excluded.

All patients received up to 2 cycles of PDT consisting of 2 PDTs 7 to 14 days apart depending on the response of the lesion to treatment. Patients then received either 10% aminolevulinic acid gel or placebo.

The primary outcome was the composite clinical and histological clearance of the main target lesions 12 weeks after start of the last PDT cycle. Key secondary efficacy outcomes included the clearance of the main target lesions per clinical or histological assessment, complete clinical clearance, and complete clearance. The clinical clearance of all target lesions after the last cycle of PDT, the 12-week composite and separate clearance rates 12 weeks after the start of the first PDT cycle, and aesthetic outcome after the last cycle of PDT were also assessed.

What were the additional efficacy and safety data from the phase 3 trial?

Further efficacy data showed that the clinical clearance rates in the investigational and placebo arms were 83.4% vs 21.4%, respectively (P < .0001). The respective histological clearance rates were 75.9% vs 19.0% (P < .0001). Most patients in the investigational arm (89.3%) reported very good or good aesthetic outcomes after treatment compared with 58.0% of patients in the placebo arm.

In terms of safety, all patients in the investigational arm experienced an any-grade treatment-emergent adverse effect (TEAE) compared with 69.0% of those in the placebo arm. The most common any-grade TEAEs in both arms included application site pain (95.2% vs 28.6%), application site erythema (69.0% vs 35.7%), and application site pruritus (50.3% vs 26.2%). No deaths were reported in either arm, and no TEAEs led to treatment discontinuation.

“The efficacy, tolerability, and aesthetic outcomes demonstrated in the phase 3 study and highlighted in our publication reinforce the value of [aminolevulinic acid gel]–PDT for the treatment of [patients with] sBCC. I look forward to potentially having this as an approved option for my patients with sBCC,” Todd Schlesinger, MD, FAAD, FASMS, the first author on the study,added in the news release.1

Schlesinger is also the founder and director of the Clinical Research Center of the Carolinas in Charleston, South Carolina.

References

1. Biofrontera Inc. announces filing of supplemental new drug application (sNDA) for the treatment of superficial basal cell carcinoma (sBCC) with Ameluz-PDT. News release. Biofrontera Inc. December 2, 2025. Updated December 2, 2025. https://investors.biofrontera-us.com/full-news/?qm-storyId=6097744969931206
2. Schlesinger T, Chapman MS, Tu JH, et al. Red light photodynamic therapy with 10% aminolevulinic acid gel showed efficacy for treatment of superficial basal cell carcinoma in a randomized, vehicle controlled, double-blind, multicenter phase III study. J Am Acad Dermatol. 2025;93(6):1489-1498. doi:10.1016/j.jaad.2025.08.031