Afamelanotide

What is afamelanotide?

Afamelanotide (SCENESSE®, Clinuvel Pharmaceuticals) is a potent alpha-melanocyte-stimulating hormone (αMSH) analogue, which stimulates the production of eumelanin in the skin — a tan, induces antioxidant activities, enhances DNA repair processes, and modulates inflammation. This injectable synthetic melanotropic peptide was previously known as Melanotan I.

Eumelanin is a form of melanin, the tanning pigment in the skin. Production of melanin is usually stimulated by exposure to the ultraviolet (UV) radiation component of sunlight.

• Exposure to UV radiation causes cellular damage that increases the risk of skin cancer.
• A tan protects the skin from further damage by absorbing UV radiation.
• Melanin also filters out longer wavelengths, providing protection to people with visible light photosensitivity.
• Melanin also has antioxidant effects to protect skin against free radicals. Free radicals are responsible for the symptoms experienced in erythropoeitic protoporphyria.

What skin conditions respond to afamelanotide?

Afamelanotide is registered, in some countries, to treat erythropoietic protoporphyria. It has been reported to be of benefit to patients with:

• Solar urticaria
• Polymorphic light eruption
• Vitiligo
• Hailey-Hailey disease

Erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is a rare, inherited disorder of metabolism typically manifesting in early childhood as painful photosensitivity. One to 20 minutes after sun exposure, patients experience burning pain on exposed skin, usually hands and face, followed by swelling and redness that lasts for several days. The fear of this pain can have a major effect on quality of life including work and recreational opportunities.

Afamelanotide has been shown through Phase III studies to decrease phototoxic reactions and recovery time in patients with erythropoietic protoporphyria. Afamelanotide was approved for treatment of erythropoietic protoporphyria by the European Medicines Agency (EMA) in 2016 and by the FDA in the US in October 2019. It reduces pain and allows nearly all patients to be outdoors for longer periods than previously. However it has no effect on the number or duration of phototoxic reactions. Quality of life is significantly improved. Sunlight avoidance and wearing protective clothing remains essential; afamelanotide is not a cure for EPP.

Solar urticaria

Solar urticaria is a rare form of chronic physical or inducible urticaria characterized by itch, weal and flare within minutes of sunlight exposure. The action spectrum (the part of the electromagnetic spectrum that causes symptoms) is variable, but most often involves long wavelength UVA and visible light. The use of afamelanotide has been shown under experimental conditions to reduce weal formation secondary to increased melanisation.

Vitiligo

Vitiligo is a disorder characterised by white patches of skin due to selective loss of epidermal melanocytes. UVB phototherapy is a cornerstone of vitiligo management; however repigmentation has been shown to be faster and superior when phototherapy is used in conjunction with afamelanotide.

Hailey-Hailey disease

Afamelanotide was prescribed to 2 patients with Hailey-Hailey disease (benign familial pemphigus) resulting in remission.

Does afamelanotide work as a sunscreen?

The use of afamelanotide has been associated with a 50% decrease in epidermal sunburn cells, as well as a significant reduction in thymine dimer formation (part of the process by which UVB damages DNA). However, the marketers of afamelanotide do not recommend its use as a sunscreen or treatment of sunburn.

Contraindications to afamelanotide

Because no data is available, contraindications to afamelanotides include:

• Liver or kidney impairment: the metabolism of this drug is not completely understood.
• Children: the safety and efficacy of this drug in people aged 0 to 17 years has not yet been established.
• The elderly: it is also recommended that patients over 70 do not take afamelanotide.
• Pregnancy: it is recommended that women who are pregnant or breastfeeding should not take it.

How to take afamelanotide

Afamelanotide (Scenesse®) comes as a white rod approximately 1.7 cm in length and 1.5 mm in diameter. It contains 16 mg of afamelanotide and is implanted under the skin, usually around the hip. It should be inserted by a specialist physician every 2 months, prior to and during increased sunlight exposure (eg, summer). It is recommend to have three implants per year, with a maximum of four per year.

The patient is asked to wait for 30 minutes in case of allergic reaction to it.

Tests before/after starting afamelanotide

Tests before starting afamelanotide may include:

• Liver and kidney function
• Pregnancy test

Additional tests may be necessary for those with heart or breathing problems, diabetes, Cushing disease, Addison disease, Peutz-Jeghers syndrome, epilepsy, anaemia or skin cancer.

Regular full-body skin examinations are recommended prior to and every six months during treatment to assess and monitor pigmented lesions and other skin abnormalities, especially in those with a personal history of skin cancer.

Side effects of afamelanotide

Few major side effects have been reported thus far.

• One-third of patients experience hyperpigmentation at the implant site
• There is a low risk of darkening moles anywhere on the body
• Mild tiredness, headache, dizziness and nausea are common after administration of the implant usually clears by 72 hours.

There is no evidence that afamelanotide increases the risk of melanoma. The primary risk factor for melanoma is UVB irradiation. Eumelanin production reduces UVB skin penetration and scavenges free radicals, hence protecting the skin.

Drug interactions with afamelanotide

Due to the method of administration, patients taking blood thinning medication may experience bruising or bleeding at the site of implantation.

No specific drug interactions have been identified to date (2015).

Safety measures

• Women of childbearing potential should use effective contraception during treatment with afamelanotide, and for a period of three months after.
• Patients are recommended not to drive or use heavy machinery within 72 hours of administration of afamelanotide due to the risk of tiredness and dizziness.

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).