Red Light Photodynamic Therapy with 10% Aminolevulinic Acid Gel Showed Robust Efficacy for the Treatment of Superficial BCC in a Randomized, Vehicle-Controlled, Double-Blind, Multicenter Phase III Study

Introduction: Basal cell carcinoma (BCC) is often treated surgically; however, depending on lesion size, location, or patient preference, surgery may not be the best option. Photodynamic therapy (PDT) has emerged as one alternative treatment for low-risk tumors like superficial BCC (sBCC). With this phase III study, we evaluated the efficacy and safety of red light PDT with 10% 5-aminolevulinic acid (ALA) gel versus vehicle in participants with sBCC. Methods: This phase III, multicenter, randomized, double-blind, vehicle-controlled, parallel group study (NCT03573401) was conducted at 21 U.S. centers. Eligible participants had at least one naïve, histologically confirmed sBCC on the face, scalp, neck/trunk and/or extremities. One lesion per participant was defined as the main target lesion (MTL) for mandatory final excision. Additional lesions were treated but not excised. Either 10% ALA gel (BF-200 ALA, Ameluz®) or vehicle was applied to the lesions and incubated under occlusion for 3 to 3.5 hours, followed by illumination with BF-RhodoLED® (10 min, 635 nm, 37 J/cm²). Treatment was administered in PDT cycles (2 PDT sessions per cycle) with a maximum of 2 PDT cycles per participant. Clinical and histological assessments were performed 12 weeks after start of the last PDT cycle. Results: Of the 187 randomized participants, 145 received 10% ALA gel and 42 received vehicle. Treatment with ALA gel resulted in significantly higher clearance rates compared with vehicle across all respective endpoints (p<0.0001 for all clearances). Clinical clearance of MTLs was achieved in 83.4% of patients in the ALA group versus 21.4% in the vehicle group. Histological clearance of MTLs was similarly superior with ALA gel (75.9% vs. 19.0%). Composite clearance of MTLs, defined as both clinical and histological clearance of MTLs, was observed in 65.5% of ALA-treated participants compared with only 4.8% in the vehicle group. Complete clinical clearance was achieved by 82.1% of participants treated with the ALA gel versus 21.4% of participants treated with vehicle. Combined clinical and histological clearance was achieved by 64.1% of participants in the ALA group versus 4.8% in vehicle. Overall clinical lesion clearance was also higher with ALA (82.6% vs. 21.6%). Esthetic outcomes were favorable in both groups but consistently better with ALA gel. Investigators rated 89.3% of ALA-treated lesions as having a very good or good cosmetic result, compared with 58.0% of vehicle-treated lesions. Participant-reported satisfaction was high regardless of treatment group, with 88.1% of lesions treated with ALA gel and 74.0% of vehicle-treated lesions rated as very good or good. No previously unknown adverse reaction occurred. Conclusion: PDT with 10% ALA gel demonstrated significantly higher clearance rates versus vehicle, with favorable safety and aesthetic outcomes. These results support red light PDT with 10% ALA gel as a highly suitable non-surgical option for sBCC, particularly for multiple or large lesions, in low-risk areas, when patients either decline surgery or are not a good candidate for surgery. The study was sponsored by Biofrontera Bioscience GmbH.