Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Biofrontera Pharma GmbH on +49 214 876 32 66 or Ameluz@biofrontera.com
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What is 5-aminolaevulinic acid?

5-aminolaevulinic acid (5-ALA) is a non-proteinogenic amino acid found in humans as a heme precursor in porphyrin synthesis in all cells.
In dermatology, 5-ALA is used as a prodrug in photodynamic therapy (PDT). After entering the cells, 5-ALA is metabolized to the photosensitizer protoporphyrin IX (PpIX).1,2

In contrast to healthy cells, neoplastic cells exhibit alterations in cellular ALA uptake, heme biosynthesis, mitochondrial functions, and PpIX efflux mechanisms.3 These changes lead to up to four times greater accumulation of PpIX in neoplastic cells, which is the basis for selective destruction of such cells in the context of PDT.4
Selective destruction is started by exposure to light during PDT5 (see Fig. 1):

  • PpIX is activated by light at appropriate wavelength.
  • The activated PpIX reacts with oxygen. Reactive oxygen species are formed in the process.
  • The reactive oxygen species lead to the selective destruction of the diseased cells.
Figure 1: The active substance 5-ALA penetrates into the skin and accumulates particularly strongly in the damaged cells (left). 5-ALA produces an increase in the photoactive compound protoporphyrin IX, which when activated by light at certain wavelengths, forms reactive oxygen species. These ultimately cause the destruction of the damaged cells (right).

Topical formulations of 5-ALA (for example in Ameluz® (78 mg/g 5-aminolaevulinic acid gel)) and the methyl ester are licensed for use in the UK. The methyl ester differs from endogenously occurring 5-ALA by the addition of a methyl group. However, an additional enzymatic step is needed to cleave this off during PpIX metabolism. There are no relevant differences in selectivity for neoplastic cells between 5-ALA and the methyl ester.4

References

  1. Reinhold U. Future Oncol 2017;13:2413-2428.
  2. Van Hillegersberg et al. Gastroenterology 1992;103:647-651.
  3. Yang X et al. Int J Mol Sci 2015;16:25865-25880.
  4. Schulten R et al. Naunyn Schmiedebergs Arch Pharmacol 2012;385:969-979.
  5. Ameluz® Summary of Product Characteristics.

 

UKBF-2022-006f-V01, Date of preparation: June 2022