FDA Accepts sNDA for Photodynamic Therapy in Superficial Basal Cell Carcinoma

The FDA accepted the supplemental new drug application (sNDA) for aminolevulinic acid hydrochloride 10% topical gel (Ameluz) as part of photodynamic therapy (PDT) for superficial basal cell carcinoma (sBCC).¹ 

The application seeks to expand the current indication of the drug used in combination with the RhodoLED red-light lamp series from its existing approval for actinic keratosis. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of September 28, 2026.

Addressing the Prevalence of sBCC

BCC remains the most frequently diagnosed malignancy in the United States, with an estimated 3.6 million new cases annually.² Although BCC is rarely metastatic, its potential for local destruction and the sheer volume of cases present a significant burden on dermatologic and oncologic practices. sBCC represents approximately 10% to 25% of these diagnoses.^3-5

Currently, the standard of care often involves surgical excision, Mohs micrographic surgery, or destructive techniques such as electrodessication and curettage. These methods can lead to scarring, permanent pigmentary changes, and may be less desirable for patients with multiple lesions or those seeking noninvasive alternatives.

Aminolevulinic acid hydrochloride is currently FDA-approved for the treatment of actinic keratosis. Its efficacy is rooted in a nanoemulsion formulation of aminolevulinic acid (ALA), a precursor to the photosensitizer protoporphyrin IX (PpIX).

Supporting Evidence

In the double-blind, randomized, placebo-controlled, multi-center study phase 3 ALA-BCC-CT013 trial (NCT03573401), 187 patients were randomly assigned on a 4:1 basis to receive PDT for 1 to 2 cycles with the topical gel or vehicle (placebo).⁶ They received clinical and histological assessment 12 weeks after start of the last PDT cycle. The primary end point of complete histological and clinical clearance of a target lesion at 12 weeks was met, resulting in 65.5% with the ALA gel vs 4.8% with placebo.

Histological clearance was 75.9% with ALA gel vs 19.0% with placebo, and clinical clearance was 83.4% with the ALA gel vs 21.4% with placebo. For 89.3% of lesions treated with the ALA gel, the aesthetic outcome was rated very good or good, compared with 58.0% in those treated with placebo.

In terms of safety, there were 1024 treatment-emergent adverse events (TEAEs) possibly related to treatment in the experimental arm, 62.4% of which were mild, 31.0% were moderate, and 6.2% were severe. No TEAEs led to treatment discontinuation. TEAEs occurred at the application site and included pain, erythema, pruritus, edema, paresthesia, scab, and exfoliation. Most of the frequent events had a median duration of less than or up to 1 week.

Clinical Implications and Next Steps

If approved, aminolevulinic acid hydrochloride would become the first and only PDT photosensitizer indicated for sBCC in the United States, offering a nonsurgical pathway that may be preferred for sBCC in cosmetically sensitive areas or in patients for whom surgery is contraindicated.

Investigators in the phase 3 trial discussed that in patients without full clearance had decreased size of lesions, giving this therapy a potential role as neoadjuvant therapy to reduce the burden of surgical excision.

Additionally, according to Biofrontera’s product pipeline, a phase 3 study of this therapy for squamous cell carcinoma in situ is in preparation.⁷

Hermann Luebbert, PhD, CEO of Biofrontera, noted that the FDA identified no filing deficiencies, signaling a robust data package. “This milestone represents an important step forward in our strategy to expand the clinical utility of [aminolevulinic acid hydrochloride] and reinforce [PDT] as a versatile platform in dermatology,” he stated in a news release. ¹

REFERENCES

1. Biofrontera announces FDA filing acceptance of supplemental new drug application for Ameluz® PDT in superficial basal cell carcinoma. News release. Biofrontera Inc. February 11, 2026. Accessed February 12, 2026. https://tinyurl.com/ye22pfps

2. Basal cell carcinoma information. Skin Cancer Foundation. Accessed February 12, 2026. https://tinyurl.com/3hfc8rbw

3. Cameron MC, Lee E, Hibler BP, et al. Basal cell carcinoma: Epidemiology; pathophysiology; clinical and histologic subtypes; and disease associations. J Am Acad Dermatol. 2019;80(2):303-317. doi:10.1016/j.jaad.2018.03.060

4. Cameron MC, Lee E, Hibler BP, et al. Basal cell carcinoma: Contemporary approaches to diagnosis, treatment, and prevention. J Am Acad Dermatol. 2019;80(2):321-339. doi:10.1016/j.jaad.2018.02.068

5. Marzuka AG, Book SE. Basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. Yale J Biol Med. 2015;88(2):167-179. Published 2015 Jun 1.

6. 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

7. Product Pipeline. Biofrontera Inc. Accessed February 12, 2026. https://tinyurl.com/ucxsdcnw