Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: photonamic GmbH & Co. KG, Eggerstedter Weg 12, 25421 Pinneberg, Germany
Pharmacotherapeutic group:: Sensitisers used in Photodynamic/Radiation therapy
ATC Code: L01XD04
After topical application of 5-aminolevulinic acid, protoporphyrin IX (PPIX) accumulates intracellularly in the treated AK lesions. The intracellular PPIX is a photoactive, fluorescing compound and, upon light activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments of the light-exposed target cells, in particular the mitochondria.
With regard to clinical safety and efficacy, Alacare was compared with placebo treatment, in a randomised observer blinded clinical trial which enrolled 107 patients with a follow-up duration of 6, 9 and 12 months. All patients had a minimum of 3 mild to moderate AK lesions on the head and/or face. Alacare was applied to AK lesions for 4 hours without preparation of the lesion, after which they were illuminated with red light at λ 630 ± 3 nm (37 J/cm²).
12 weeks after treatment, complete clinical clearance on lesion and on patient basis of a once-only photodynamic therapy with Alacare was statistically significantly more effective than photodynamic therapy with placebo. This was sustained during follow-up, in which patients were seen every 3 months (after 6, 9 and 12 months). In an open randomised trial, which enrolled 349 patients, Alacare PDT in the same regime as described above, was compared with cryosurgery and placebo-PDT. In this trial, Alacare-PDT proved non-inferior to cryosurgery. After 12 weeks in the Full Analysis Set 87% of lesions treated with Alacare-PDT were cleared, compared to 77% after cryosurgery (Odds Ratio 1.86; 95% CI [1.18, 2.93]) and 32% after placebo-PDT. Differences were sustained during the complete follow-up period (after 6, 9 and 12 months). Recurrence rates of cleared lesions 12 months after therapy were 12% for Alacare-PDT and 18% for cryosurgery (Odds Ratio 0.627; 95% CI [0.461, 0.854]).
Pharmacokinetic data from a clinical trial in patients with mild to moderate actinic keratoses on the head and/or face, who had 8 Alacare plasters applied for 4h, showed a baseline corrected Cmax of 16.4 µg/L and an AUC0-24 of 101.4 µg*h/L of systemic exogenous 5-aminolevulinic acid. Tmax was at 4 hours. The excretion of 5-ALA in urine during the first 12 hours after application was low. The maximum excretion was 2.06% of the total dose, the median was 1.39%.
PPIX was not detected in any of the plasma samples.
In another clinical trial in 12 AK patients with mild to moderate AK lesions on the head and/or face, it could be shown that Alacare-induced PPIX specific fluorescence is higher in AK lesions than in normal skin and increases with duration of the Alacare exposure. However, extending application interval beyond 4h did not result in higher PPIX fluorescence.
Preclinical studies on general toxicity and genotoxicity studies in the presence or absence of photoactivation, do not indicate potential risks for man. Conventional carcinogenicity studies have not been performed with 5-aminolevulinic acid. Studies reported in the literature do not indicate a carcinogenic potential. Studies on the reproductive function have not been performed.
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