Phase III Trial of Afamelanotide 16 mg Subcutaneous Bioresorbable Implants for the treatment of Erythropoietic Protoporphyria. R. J. Desnick1, K. E. Anderson2, D. M. Bissell3, J. R. Bloomer4, H. L. Bonkovsky5, M. Lebwohl6, H. Lim7, C. Parker8, J. Phillips8, H. Naik1, M. Balwani1 1) Dept Gen/Genomic Sci, Box 1498, Mount Sinai Sch Med, New York, NY; 2) Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX; 3) Department of Medicine, University of California, San Francisco, CA; 4) Department of Medicine, University of Alabama at Birmingham, AL; 5) Department of Medicine, Carolinas Medical Center and Healthcare system, Charlotte, NC; 6) Department of Dermatology, Mount Sinai School of Medicine; 7) Department of Dermatology, Henry Ford Health System, Detroit, MI; 8) Department of Internal Medicine, University of Utah, Salt Lake City, UT.

   Erythropoietic Protoporphyria (EPP) is a rare, autosomal recessive photodermatosis resulting from deficient activity of the heme biosynthetic enzyme, ferrochelatase, and the resultant erythroid accumulation of photoactive protoporphyrin IX. When EPP patients are exposed to sunlight, a phototoxic reaction is triggered resulting in incapacitating pain. There is no effective treatment and patients avoid sun exposure which significantly impacts their daily life activities and overall quality-of-life (QoL). Afamelanotide, in the form of a subcutaneously administered, bioresorbable implant is a potent analogue of alpha-melanocyte stimulating hormone (-MSH) and stimulates the production of eumelanin in the skin epidermis. Melanin, in the form of eumelanin, is a photoprotective agent and the postulated mechanism of afamelanotide photoprotection includes the absorption and scattering of UV light, free radical scavenging and quenching of UV light. To determine the safety and effectiveness of afamelanotide in increasing sun-exposure time and QoL, 93 North American patients were enrolled in a FDA-approved, multicenter, randomized, double-blind, placebo-controlled Phase III study. Afamelanotide or placebo implants were administered subcutaneously on days 0, 60 and 120, and the type and duration of sun exposure, number and severity of phototoxic reactions, and adverse events were recorded. A subset of patients underwent photoprovocation testing at baseline and during the study to determine tolerance to visible light exposure. The impact of treatment on QoL was evaluated using two validated questionnaires, the Dermatology Life Quality Index and an EPP-specific quality of life questionnaire (EPP-QoL). The primary endpoint analysis showed that treated patients were able to experience more pain free sun exposure, particularly between 10:00 to 18:00 hrs (69.4 v 40.8 hours over the entire study, p=0.044). Photoprovocation testing showed increased tolerance to visible light on the dorsum of the hand and lower back (day 90 p=0.011, p<0.001, day 120 p=0.045, p=0.028) and the EPP-QoL showed significant treatment related improvement (p=<0.001, p=0.002, p=0.028 at day 60, 90 and 180). Adverse events were mainly mild and unrelated to the study drug. These results demonstrate that afamelanotide is safe, well tolerated, and improves pain-free sun exposure and QoL in patients with EPP.

You may contact the first author (during and after the meeting) at