The US Food and Drug Administration (FDA) has approved afamelanotide (Scenesse, Clinuvel), the first treatment to ease phototoxic reactions in patients with erythropoietic protoporphyria, according to an agency news release. Erythropoietic protoporphyria is a rare condition resulting from mutations that limit the activity of the enzyme ferrochelatase, which is involved in heme production. The fall in ferrochelatase activity causes protoporphyrin IX (PPIX) to accumulate in the body. When light reaches the skin, it can react with PPIX, resulting in severe skin pain and skin changes, including redness and thickening. Afamelanotide is a melanocortin-1 receptor agonist that increases eumelanin production in the skin regardless of exposure to sunlight or artificial light. "For patients who are suffering from erythropoietic protoporphyria, a rare disorder, exposure to light may be extremely painful. Prior to today's approval, there were no FDA-approved treatments to help erythropoietic protoporphyria patients increase their light exposure," Julie Beitz, MD, director of the FDA's Center for Drug Evaluation and Research Office of Drug Evaluation III, said in the release. "Today's approval is one example of the FDA's ongoing commitment to encourage industry innovation of therapies to treat rare diseases and work with drug developers to make promising new therapies available to patients as safely and efficiently as possible," Beitz added. The European Medicines Agency backed the treatment in 2014 in a positive opinion, as reported by Medscape Medical News. Two Clinical Trials The FDA's decision was based on the results of two parallel-group clinical trials in patients with erythropoietic protoporphyria. The first study enrolled 93 participants; 48 received a subcutaneous implant containing afamelanotide bimonthly, and the others received a subcutaneous implant containing placebo bimonthly. Participants were followed for 180 days. The primary outcome was the total number of hours during 180 days that the patient spent in direct sunlight between 10:00 AM and 6:00 PM on days without pain. Those in the afamelanotide group spent 64 hours in direct sunlight, whereas those in the placebo group spent 41 hours. The second clinical trial included 74 patients who were followed for 270 days. Of those, 38 patients received afamelanotide. The primary outcome was the total number of hours spent outdoors between 10:00 AM and 3:00 PM during those 270 days on which they had spent "most of the day" in direct sunlight without pain. For patients in the afamelanotide group, the median total number of hours was 6, compared with 0.75 hours for those in the placebo group. The researchers did not conduct analyses for sun exposure on days in which patients spent time both in direct sunlight and in shade. The most frequently seen adverse effects are "implant site reaction, nausea, oropharyngeal (part of the throat just behind the mouth, where the oral cavity starts) pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus (moles), respiratory tract infection, somnolence (feeling drowsy), non-acute porphyria (build-up of normally occurring molecules created during heme production) and skin irritation," according to the FDA news release. Only healthcare professionals skilled in the subcutaneous implantation procedure who have completed the applicant-provided training should administer afamelanotide. Afamelanotide may cause skin darkening, and patients should undergo a full body skin examination twice per year. The FDA also urges patients to use sun protection measures while receiving afamelanotide treatment. The agency gave this application priority review designation and orphan drug designation. Source
