Photodynamic therapy with BF‐200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer‐blind phase III study in comparison with a registered methyl‐5‐aminolaevulinate cream and placebo (Dirschka et al., 2012, Dirschka et al., 2013)^2,3

This randomized, observer-blind phase III trial with a total of 571 patients investigated the efficacy and safety of conventional PDT with Ameluz® in the treatment of AK on the face and scalp in comparison with an active comparator (MAL [methyl (5-amino-4-oxopentanoate] cream) and placebo. The red light source was either a lamp with a narrow spectrum or with a broader and continuous spectrum. Efficacy was assessed 3 months after treatment, and persistent lesions were followed up with another PDT.

Results: Complete patient clearance 12 weeks after the last PDT (primary endpoint) was 78.2% for Ameluz®, 64.2% for MAL cream and 17.1% for placebo. Ameluz® was significantly more effective than MAL cream and placebo and proved superior in terms of the complete patient clearance (p<0.05 and p<0.0001, respectively).^1,2 Clinical efficacy was reassessed at follow-up examinations 6 and 12 months after the last PDT. The lesion recurrence rate 12 months after the last PDT was slightly better for Ameluz® (21.7%) than for the MAL cream (25.4%).^1,3 The clearance rates were dependent on the type of lamp used for exposure, with results in favor of narrow spectrum lamps.^1-3

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Photodynamic therapy with BF‐200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double‐blind, placebo‐controlled phase III study (Szeimies et al., 2010, Dirschka et al., 2013)3,4
This randomized, double-blind phase III trial with a total of 122 patients investigated the efficacy and safety of conventional PDT with Ameluz^® in the treatment of AK on the face and scalp compared with placebo. The red light source was either a lamp with a narrow spectrum or with a broader and continuous spectrum. Efficacy was assessed 3 months after treatment, and persistent lesions were followed up with another PDT.

Results: Complete patient clearance 12 weeks after the last PDT (primary endpoint) was 66.3% for Ameluz^® compared with 12.5% for placebo. Therapy with Ameluz^® was significantly superior to placebo treatment in terms of both complete patient and total lesion clearance (p<0.0001).^1,4 Clinical efficacy was reassessed at follow-up examinations 6 and 12 months after the last PDT. The lesion recurrence rate 12 months after the last PDT was 16.7% for Ameluz^®.^1,3 The clearance rates were dependent on the type of lamp used for exposure, with results in favor of narrow spectrum lamps.^1,3,4

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A randomized, double‐blind, phase III, multicentre study to evaluate the safety and efficacy of BF‐200 ALA (Ameluz^®) vs. placebo in the field‐directed treatment of mild‐to‐moderate actinic keratosis with photodynamic therapy (PDT) when using the BF‐RhodoLED^® lamp (Reinhold et al., 2016)⁵

This randomized, double-blind phase III trial with a total of 87 patients was the first to investigate the efficacy and safety of conventional PDT with Ameluz^® in the field-directed treatment of AK (field cancerization) on the face and scalp in comparison with placebo. The red light source (BF-RhodoLED^®) provided a narrow spectrum of 635 nm at a light dose of 37 J/cm2. Efficacy was assessed 3 months after treatment, and persistent lesions were followed up with another PDT.

Results: Complete patient clearance 12 weeks after the last PDT (primary endpoint) was 90.9% for Ameluz^® compared to 21.9% for placebo. Ameluz^® proved to be significantly superior to placebo in terms of both complete patient and total lesion clearance (p<0.0001). Clinical efficacy was reassessed at follow-up visits 6 and 12 months after the last PDT. The lesion recurrence rate 12 months after the last PDT was 9.1% for Ameluz^®. In addition, this study assessed skin quality in the treated area at baseline and 6 and 12 months after the last PDT. All skin quality parameters improved continuously until month 12 of follow-up.^1,5

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A randomized, double-blind, intra-individual, multi-center phase III study to evaluate the safety and efficacy of BF-200 ALA (Ameluz^®) versus placebo in the treatment of mild to severe actinic keratosis on extremities, trunk/neck with photodynamic therapy (PDT) when using the BF-RhodoLED^® lamp (Ulrich et al., 2021)⁶

This randomized, double-blind, intraindividual phase III trial with a total of 50 patients investigated the efficacy and safety of conventional PDT with Ameluz^® in the field-directed treatment of AK on the extremities, trunk and neck in a half-side comparison with placebo treatment. The red light source (BF-RhodoLED®) provided a narrow spectrum of 635 nm at a light dose of 37 J/cm2. Efficacy was assessed 3 months after treatment, and persistent lesions were followed up with another PDT.

Results: Total lesion clearance per patient side 12 weeks after the last PDT (primary endpoint) was 86.0% on average for Ameluz^® compared with 32.9% for placebo. Ameluz^® also proved to be significantly superior to placebo in all other efficacy parameters.^1,6 Clinical efficacy was reassessed at follow-up examinations 6 and 12 months after the last PDT. The lesion recurrence rate 12 months after the last PDT was 14.1% for Ameluz^®.⁶

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A randomized, intraindividual, non-inferiority, Phase III study comparing daylight photodynamic therapy with BF-200 ALA gel and MAL cream for the treatment of actinic keratosis (Dirschka et al., 2019)⁷

This randomized, observer-blind, intraindividual phase III study investigated the efficacy and safety of daylight PDT with Ameluz^® in the treatment of AK on the face and scalp in a half-side-by-side comparison with a MAL cream. A total of 52 patients, each with 3-9 AK on both sides of the face and/or scalp, were treated with one of the two drugs. PDT was performed outdoors for 2 continuous hours in full daylight.

Results: Total lesion clearance per patient side 12 weeks after a single daylight PDT (primary endpoint) was 79.8% on average for Ameluz^® compared with 76.5% for the MAL cream, with a comparable safety and tolerability profile. The study was able to demonstrate the non-inferiority of Ameluz^® compared to MAL cream. Clinical efficacy was reassessed at follow-up visits 6 and 12 months after daylight PDT. The lesion recurrence rate 12 months after a single daylight PDT was a mean of 19.9% for Ameluz^® and a mean of 31.6% for MAL cream.⁷

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A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy (Morton et al., 2018)⁸

This randomized, observer-blind phase III trial investigated the efficacy and safety of conventional PDT with Ameluz^® for the treatment of non-aggressive BCC (superficial BCCs and nodular BCCs ≤ 2 mm) compared with MAL cream. A total of 281 patients with 1-3 BCCs were initially treated with two sessions of red light PDT approximately one week apart. The efficacy evaluation was conducted 3 months after treatment. Persistent lesions were followed up with another cycle of 2 PDT sessions. The red light source used (BF-RhodoLED^®) produced a narrow spectrum of about 635 nm at a light dose of 37 J/cm².
 
Results: Complete patient clearance 12 weeks after the last PDT (primary endpoint) was 93.4% for Ameluz^® compared with 91.8% for the comparator product MAL cream. The lesion recurrence rates at 6 and 12 months were 2.9% and 6.7% for Ameluz^® and 4.3% and 8.2% for MAL. The study demonstrated the non-inferiority of Ameluz^® to MAL cream as well as a comparable safety and tolerability profile.^1,8

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