10% ALA Gel With PDT Demonstrates High Clearance Rates in Superficial BCC

Red light photodynamic therapy (PDT) with 10% 5-aminolevulinic acid (ALA) gel demonstrated higher clearance rates and positive esthetical outcomes compared to vehicle in basal cell carcinoma (BCC).1

“Ten percent ALA gel is a nanoemulsion-based formulation of 10% ALA hydrochloride, equaling 7.8% ALA. Upon topical administration, skin cells absorb and metabolize ALA to the photosensitive protoporphyrin IX (PpIX), which accumulates in neoplastic cells. Illumination at appropriate wavelengths activates PpIX, resulting in specific destruction of neoplastic cells.2 10% ALA gel is currently approved for field- directed treatment of actinic keratosis on face and scalp in the US. In Europe, it is additionally approved for actinic keratosis on the trunk and extremities, field cancerization, sBCC, and nodular BCC,” study investigator Todd Schlesinger, MD, Clinical Research Center of the Carolinas, Charleston, South Carolina, and colleagues wrote.1

Schlesinger and colleagues conducted the randomized, double-blind, vehicle-controlled, pivotal phase 3 study at 21 centers in the United States. The study treated 145 participants (of 187 randomized) with ≥1 naïve superficial BCC with 1-2 PDT cycles (2 PDTs each cycle) followed by clinical and histological assessment 12 weeks after start of the last PDT cycle, randomized to receive 10% ALA gel (n = 145) or vehicle (n = 45).1

The investigators found that those receiving 10% ALA gel had a 75.9% histological clearance rate and an 83.4% clinical clearance rate compared with 19.0% and 21.4%. respectively, in those receiving vehicle (both P <.0001). Baseline size of the main target lesions (MTLs) slightly affected clearance rates, which decreased with increasing size (clinical clearance: 90.7% at £81 mm2; 88.0% at 84-160 mm2; 73.1% at £165 mm2; histological clearance: 86.0% at £81 mm2; 74.0% at 84-160 mm2; 69.2% at £165 mm2). After the first PDT cycle, 83 MTLs (57.2%) treated with 10% ALA gel and 6 MTLs (14.3%) treated with vehicle reached clinical clearance. Investigators excised and confirmed histological clearance in 64 MTLs (44.1%) treated with 10% ALA gel and in 1 MTL (2.4%) treated with vehicle.1

After the last PDT cycle, 82.1% of participants treated with 10% ALA gel and 21.4% of those treated with vehicle achieved complete clinical clearance (P <.0001). Complete clinical and histological clearance was observed in 64.1% of the 10% ALA gel group versus 4.8% in the vehicle group (P <.0001). Clinical lesion clearance was also higher with 10% ALA gel compared to vehicle (82.6% vs 21.6%). Among noncleared lesions, size was reduced in 23 of 30 with 10% ALA gel and 19 of 40 with vehicle, with median size change of –41.9% vs no change, respectively. Esthetic outcomes were rated very good or good in 89.3% of 10% ALA gel–treated lesions versus 58.0% of vehicle-treated lesions. Participant satisfaction was high in both groups, with very good or good esthetic outcomes reported for 88.1% of lesions in the 10% ALA gel group and 74.0% in the vehicle group; most would choose treatment again (95.0% vs 100.0%).1

There were no previously unknown adverse events (AEs) reported. Most related treatment emergent AEs were of mild intensity and lasted under a week (except site discoloration, which lasted longer).

“Ten percent ALA gel achieved significantly higher clearance rates than vehicle, with favorable safety and positive esthetic outcome. The high efficacy, good tolerability, and cosmetic benefits demonstrated in our study reinforce the value of red light PDT with 10% ALA gel as highly suitable alternative to surgical excision for the treatment of sBCC, especially for multiple or large lesions, in low risk areas, or where patients oppose surgery. Additionally, PDT has great potential as an adjunctive therapy to surgical excision, as the burden for patients may be reduced due to removal of less tissue,” Schlesinger and colleagues concluded.1

References

1. Schlesinger T, Chapman MShane, 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. Published online August 2025. doi: 10.1016/j.jaad.2025.08.031

2. Schmitz L, Novak B, Hoeh AK, Luebbert H, Dirschka T. Epidermal penetration and protoporphyrin IX formation of two different 5-aminolevulinic acid formulations in ex vivo human skin. Photodiagnosis Photodynamic Thery. 2016;14:40-46. doi: 10.1016/j.pdpdt.2015.11.004