Phase 3 Evidence Supports Ameluz Photodynamic Therapy for Actinic Keratosis
Phase 3 clinical trial results demonstrate that Ameluz photodynamic therapy is an effective treatment for actinic keratoses on the neck, trunk, and extremities. The therapy met its primary endpoint and showed highly statistically significant superiority compared with vehicle gel, supporting its clinical efficacy across multiple body sites.
The multicenter, randomized, double-blind, vehicle-controlled Phase 3 study evaluated the efficacy and tolerability of field-directed Ameluz® PDT compared with vehicle PDT in patients with AKs located on the extremities, neck, and trunk. The study enrolled 172 patients, randomized 4:1 to receive Ameluz® gel or vehicle gel, respectively.
The study was designed to assess treatment of increasing field sizes through the application of one, two, or three tubes of Ameluz® over areas of approximately 80, 160, or 240 cm², applied either continuously or in patches, followed by PDT using a RhodoLED® XL or BF-RhodoLED® lamp. Patients received one PDT treatment, with a second PDT treatment administered at Week 12 if any AK lesions remained. Patients are being followed for approximately one year after their final PDT treatment.
The primary endpoint was “subject complete clearance rate,” defined as the percentage of patients with complete clearance of all treated AK lesions 12 weeks after the last PDT treatment.
Ameluz® PDT demonstrated highly statistically significant superiority over vehicle PDT for the primary endpoint. In the Full Analysis Set (FAS), complete clearance was achieved in 45.6% of patients treated with Ameluz® PDT (62/136), compared with 16.7% of patients treated with vehicle PDT (6/36) (p < 0.0003). In the Per Protocol Set (PPS), complete clearance rates were 53.2% (58/109) for Ameluz® PDT versus 22.2% (6/27) for vehicle PDT (p < 0.001).
Key secondary outcomes further supported the efficacy of Ameluz® PDT. The percentage of AK lesion clearance 12 weeks after the last PDT was 73.1% in the FAS and 80.3% in the PPS. Subject complete clearance rates by anatomical location were 38.5% (FAS) and 46.5% (PPS) on the extremities, and 74.1% (FAS) and 78.3% (PPS) on the neck and trunk.
In addition to efficacy, Ameluz® PDT demonstrated favorable cosmetic outcomes and high patient satisfaction. Investigators rated the aesthetic appearance of treated skin as “good” or “very good” in 75.2% of patients, while 70.9% of patients reported similar assessments. Consistent with these results, 86.3% of patients indicated they would choose PDT again for future treatment.
“These results represent a critical milestone in our clinical program,” said Hermann Luebbert, CEO and Chairman of Biofrontera Inc. “These data support Ameluz®’s potential to treat broader, high-burden AK fields beyond the face and scalp, significantly expanding its potential clinical use across multiple sun-exposed body areas, underscoring the potential to expand Ameluz®’s addressable market beyond the face and scalp. If approved, this label expansion would provide meaningful benefit to patients with actinic keratoses on the extremities, neck, and trunk and represent an important step forward in advancing our vision to establish leadership in photodynamic therapy.”
Nathalie Zeitouni, Professor of Dermatology at the University of Arizona College of Medicine – Phoenix and Adjunct Professor of Oncology at Roswell Park Comprehensive Cancer Center, and coordinating investigator of the study, commented: “Ameluz® PDT is already a valuable treatment option for actinic keratoses on the face and scalp. 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.”
Based on these positive Phase 3 results, Biofrontera plans to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration in the third quarter of 2026.
