Afamelanotide

Products

Afamelanotide is administered as an implant (Scenesse, Clinuvel). It has had orphan drug status in many countries since 2008. It has not yet been registered with Swissmedic and is not approved as a drug. In the United States, the drug was approved in 2019.

Structure and properties

Afamelanotide is an analog of α-melanocyte-stimulating hormone (α-MSH), which is produced in the skin by keratinocytes and is paracrine active. Afamelanotide is a peptide consisting of 13 amino acids (tridecapeptide). Two amino acids of the natural hormone were modified. A methionine (Met) was replaced by a norleucine (Nle) and an L-phenylalanine (L-Phe) was swapped with a D-phenylalanine (D-Phe) (Nle4-D-Phe7-α-MSH):

  • Afamelanotide: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val
  • Α-MSH: Ac-Ser-Tyr-Ser-Met-Glu-His-L-Phe-Arg-Trp-Gly-Lys-Pro-Val

Effects

Afamelanotide (ATC D02BB02) binds to the melanocortin-1 receptor (MC1R) on melanocytes in the skin like the natural ligand α-MSH, but has a longer binding duration. This is due in part to reduced degradation in the blood, resulting in a longer half-life. Binding to the receptor promotes the synthesis of the brown-black skin pigment eumelanin, which absorbs UV light and exerts antioxidant and anti-inflammatory properties. Afamelanotide leads – independent of solar radiation! – leads to increased skin pigmentation. It can thus also promote the development of birthmarks, freckles and skin discoloration and change hair color.

Indications

  • For prevention of phototoxicity in adult patients with erythropoietic protoporphyria.
  • Other indications include solar urticaria (urticaria solaris) and Hailey-Hailey disease.
  • Afamelanotide is also being studied for the treatment of vitiligo and other diseases.

Dosage

According to the product information. The implant, which is about the size of a grain of rice, is administered subcutaneously and dissolves in the tissue on its own, so it does not need to be removed. Increased pigmentation occurs after about two days and lasts for two months.

Contraindications

  • Hypersensitivity
  • Severe liver disease
  • Liver failure
  • Renal insufficiency

Full precautions can be found in the drug label.

Adverse effects

The most common potential adverse effects include nausea, headache, and reactions at the implant site, such as discoloration, pain, redness, and bruising.