FDA Approves Afamelanotide to Treat Erythropoietic Protoporphyria

After gaining approval from the US Food and Drug Administration (FDA), afamelanotide (Scenesse) will soon be available to treat adults with a history of phototoxic reactions from erythropoietic protoporphyria by increasing pain-free light exposure.

Scenesse, which is developed by Clinuvel, received both a Priority Review designation and Orphan Drug designation by the FDA.

"For patients who are suffering from erythropoietic protoporphyria, a rare disorder, exposure to light may be extremely painful,” Julie Beitz, MD, director of FDA's Center for Drug Evaluation and Research Office of Drug Evaluation III, said in a statement. “Prior to today's approval, there were no FDA-approved treatments to help erythropoietic protoporphyria patients increase their light exposure.”

Erythropoietic protoporphyria is a rare disorder caused by mutations leading to impaired ferrochelatase activity that leads to an accumulation of protoporphryin IX (PPIX).

Light reaching the skin can react with PPIX causing intense skin pain and skin changes, such as redness and thickening. The newly approved implantable drug, a melancortin-1 receptor (MC1-R) agonist, works by increasing the production of eumelanin in the skin independent of light exposure.

The investigators tested the drug in a pair of parallel group clinical trials involving patients with erythropoietin protoporphyria who received either Scenesse or a placebo form of the implant subcutaneously every 2 months.

In the first trial, 93 patients were followed for 180 days. The primary endpoint was the total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. pm days with no pain.

The median total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain was 64 hours for patients receiving the drug and 41 hours for patients taking the placebo.

In the second clinical trial, 74 patients were followed for 270 days. The primary endpoint was number of hours over 270 days spent outdoors between 10 a.m. and 3 p.m. on days with no pain where the majority of the day was spent in direct sunlight.

This analysis did not include sun exposure on days patients reported spending time in a combination of both direct sunlight and shade.

The median total number of hours over 270 days spent outdoors between 10 a.m. and 3 p.m. on days with no pain for which "most of the day" was spent in direct sunlight was 6 hours for patients receiving Scenesse and .75 hours for patients receiving placebo.

The most common adverse effect associated with the drug were implant site reaction, nausea, oropharyngeal pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus, respiratory tract infection, somnolence, non-acute porphyria, and skin irritation.