New Phase 3 Findings Support Ameluz-PDT for Patients with Actinic Keratosis

Positive and statistically significant topline results have been released from a phase 3 clinical study evaluating Ameluz photodynamic therapy (Ameluz PDT) for actinic keratosis (AK), with the treatment meeting its primary endpoint and showing highly statistically significant superiority versus vehicle gel.1

These data were announced on February 9 by Biofrontera Inc. These findings specifically highlight the effectiveness of Ameluz-PDT used alongside the red-light LED RhodoLED platform in the treatment of mild to moderate actinic keratoses (AKs) on the extremities, neck, and trunk.

“Ameluz® PDT is already a valuable treatment option for actinic keratoses on the face and scalp,” Nathalie Zeitouni, MD, professor of dermatology at the University of Arizona College of Medicine and coordinating investigator of this study, said in a statement.1 “Many patients present with lesions on other areas of the body, and these data support the potential for Ameluz® PDT to expand treatment options for physicians and their patients.”

Actinic keratosis is among the most frequently encountered conditions in dermatology, representing a benign intraepidermal proliferation of lesions considered a precancerous and classified as squamous cell carcinoma in situ.2 Around 25% of adults are affected by AK, with prevalence increasing with age.

Ameluz-PDT, a photodynamic therapy option, is currently being evaluated by the US Food and Drug Administration (FDA) following Biofrontera’s submission of a supplemental New Drug Application (sNDA) for superficial basal cell carcinoma (sBCC). The treatment was assessed in a multi-center, randomized, double-blind, vehicle-controlled phase 3 trial, designed to look at both the efficacy and tolerability of field-directed Ameluz PDT compared with vehicle PDT in patients who present with AKs impacting the extremities, neck, and trunk.

There were 172 patients recruited for the analysis, with Zeitouni and coauthors randomizing participants in a 4:1 ratio to be either treated with Ameluz gel or vehicle gel. In their study protocol, the team allowed for treatment of progressively larger field areas, with 1, 2, or 3 tubes of Ameluz applied to regions of approximately 80, 160, or 240 cm², administered either continuously or in discrete patches.

PDT was performed, after application, via either a RhodoLED XL or BF-RhodoLED lamp. All of those assessed were given a single PDT session, with a second treatment provided at the 12-week mark provided residual AK lesions were visible. Those evaluated are still being followed for roughly a year following their final PDT session. The investigators’ main efficacy outcome was the subjects’ complete clearance rate, defined as the proportion of individuals attaining complete clearance of all treated AK lesions 12 weeks post-final PDT treatment.

Overall, the team noted Ameluz-PDT demonstrated superiority over vehicle PDT for the study’s primary endpoint.1 In the Full Analysis Set, complete clearance was shown to have been attained in 45.6% of individuals treated with Ameluz-PDT, compared with 16.7% of those on vehicle PDT, a difference described as highly statistically significant (P < .0003).

Results were consistent in the Per Protocol Set, where complete clearance took place in 53.2% of Ameluz-treated individuals versus 22.2% of vehicle-treated subjects (P < .001).1 In their secondary analyses, Zeitouni et al further reinforced their data. Overall clearance rates of AK lesions at 12 weeks after the final PDT reached 73.1% in the Full Analysis Set and 80.3% in the Per Protocol Set. When assessed by anatomical site, subject complete clearance rates on the extremities were 38.5% in the Full Analysis Set and 46.5% in the Per Protocol Set, whereas clearance on the neck and trunk was higher, at 74.1% and 78.3%, respectively.

Outside of clinical efficacy, the use of Ameluz-PDT was linked with favorable cosmetic outcomes and strong patient-reported satisfaction in this analysis as well.1 The investigators looked at ratings of the post-therapy appearance of the skin as good or very good in 75.2% of those evaluated. They noted 70.9% of subjects reported comparable assessments. In line with these results, 86.3% of patients stated they would opt for PDT once more if future use was shown to be necessary.

On the basis of these new phase 3 results, Biofrontera has highlighted its plan to submit an sNDA to the FDA during the third quarter of 2026.1

References

1. Biofrontera Announces Positive Results in Phase 3 Study of Ameluz® PDT for Actinic Keratoses on the Extremities, Neck, and Trunk, Meeting Primary Endpoint. Biofrontera, Inc. February 9, 2026. https://www.globenewswire.com/news-release/2026/02/09/3234622/0/en/Biofrontera-Announces-Positive-Results-in-Phase-3-Study-of-Ameluz-PDT-for-Actinic-Keratoses-on-the-Extremities-Neck-and-Trunk-Meeting-Primary-Endpoint.html.

2. Ceryn J, Lesiak A, Narbutt J, et al. Actinic keratosis: comprehensive review of current treatments and emerging therapeutic innovations. Postepy Dermatol Alergol. 2025 Jan 31;42(3):221-231. doi: 10.5114/ada.2024.147331. PMID: 40672735; PMCID: PMC12262025.

3. Biofrontera Inc. Announces Filing of Supplemental New Drug Application (sNDA) for the Treatment of Superficial Basal Cell Carcinoma (sBCC) with Ameluz®-PDT. Biofrontera Inc. December 2, 2025. Accessed February 9, 2026. https://www.globenewswire.com/news-release/2025/12/02/3197970/0/en/Biofrontera-Inc-Announces-Filing-of-Supplemental-New-Drug-Application-sNDA-for-the-Treatment-of-Superficial-Basal-Cell-Carcinoma-sBCC-with-Ameluz-PDT.html.