Almost five years after the first patient-powered approvals for Clinuvel Pharmaceuticals Ltd.'s Scenesse (afamelanotide) arrived in Europe, the FDA has granted the company U.S. approval to increase pain-free light exposure in adults with a history of skin damage from the rare inherited disorder erythropoietic protoporphyria (EPP).

Scenesse was first approved in Europe in late 2014, marking the first example in which the EMA made a final assessment of a drug with substantial weight given to testimony from EPP sufferers, despite mixed clinical data at the time. (See BioWorld, Oct. 28, 2014.)

EPP affects males and females in equal numbers and is estimated to occur in one in 74,300 individuals, according to the American Porphyria Foundation.

Prior to the U.S. approval, there were no FDA-approved treatments to help EPP patients increase their light exposure. "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," said Julie Beitz, director of the FDA's Center for Drug Evaluation and Research Office of Drug Evaluation III.

The FDA granted the application a priority review as well as affording the program orphan drug status.

EPP is a rare disorder caused by mutations leading to impaired activity of ferrochelatase, an enzyme involved in heme production, according to the FDA. "Heme is an important component in hemoglobin, the oxygen-carrying molecule in red blood cells. The decrease in ferrochelatase activity leads to an accumulation of protoporphyrin IX (PPIX) in the body," the agency said. When light reaching the skin reacts with PPIX, it can cause intense skin pain and skin changes, such as redness and thickening. Scenesse, a melanocortin-1 receptor (MC1-R) agonist, increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources.

Efficacy of the medicine was established in two parallel group trials in EPP patients who received Scenesse or a placebo form of the implant every two months. The first trial enrolled 93 participants, of whom 48 received Scenesse. They 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. on 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 Scenesse and 41 hours for patients taking placebo, according to the FDA.

The second trial enrolled 74 patients, of whom 38 received Scenesse. They were followed for 270 days. The primary endpoint was the 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. The median total number of hours over 270 days spent outdoors with no pain for which "most of the day" was spent in direct sunlight during the time frame studied was six hours for patients receiving Scenesse and 0.75 hours for patients receiving placebo, the agency said.

Scenesse's most common side effects are implant site reaction, nausea, oropharyngeal pain, cough, fatigue, skin hyperpigmentation, dizziness, moles, respiratory tract infection, drowsiness, non-acute porphyria and skin irritation.

Trading in shares of Melbourne, Australia-based Clinuvel (ASX:CUV) was halted prior to the announcement and will remain so until the ASX decides to lift the halt or the start of trading on Oct. 11, whichever comes first. Prior to the halt, Clinuvel shares rose 3.7% to AU28.09 (US$18.91).

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