FDA Approves Drug for Phototoxic Reactions in Erythropoietic Protoporphyria

The U.S. Food and Drug Administration (FDA) approved Scenesse® (afamelanotide) to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria. This is the first FDA approval for this indication.

Erythropoietic protoporphyria is a rare disorder caused by mutations leading to impaired activity of ferrochelatase, an enzyme involved in heme production—a component in hemoglobin. The decrease in ferrochelatase activity leads to an accumulation of protoporphyrin IX; in these patients, light interaction can result in intense skin pain and skin changes, such as redness and thickening.

This melanocortin-1 receptor agonist is a subcutaneous implant that increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources.

Afamelanotide increases tolerance of light exposure

The approval was based on two parallel group clinical trials that included patients with erythropoietic protoporphyria who received afamelanotide or a placebo implant subcutaneously every two months. The first clinical trial included 93 patients, 48 of whom received afamelanotide. Patients were followed for 180 days. The median total number of hours over 180 days spent in direct sunlight between 10 AM and 6 PM on days with no pain (primary endpoint) was 64 hours for patients receiving afamelanotide versus 41 hours for patients receiving placebo.

The second clinical trial included 74 patients, 38 of whom received afamelanotide. Patients were followed for 270 days. The median total number of hours over 270 days spent outdoors between 10 AM and 3 PM on days with no pain for which “most of the day” was spent in direct sunlight (primary endpoint) was six hours for patients receiving afamelanotide versus 0.75 hours for patients receiving placebo.

The most common adverse events associated with afamelanotide include implant site reaction, nausea, oropharyngeal pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus, respiratory tract infection, somnolence, non-acute porphyria, and skin irritation. Afamelanotide may induce skin darkening, and it is recommended that patients undergo a full body skin examination twice per year. Patients should also maintain sun protection measures during treatment with afamelanotide to prevent phototoxic reactions related to erythropoietic protoporphyria.