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Afamelanotide for Erythropoietic Protoporphyria.

Janneke G Langendonk1, Manisha Balwani1, Karl E Anderson1

  • 1The Department of Internal Medicine, Center of Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam (J.G.L., F.P.J.K., E.J.G.S., F.W.M.R., J.H.P.W.), and the Department of Dermatology, Maastricht University Medical Center, Maastricht (J.F.) - both in the Netherlands; the Departments of Genetics and Genomic Sciences (M.B., H.N., R.J.D.) and Dermatology (M.L.), Icahn School of Medicine at Mount Sinai, New York; the Departments of Preventive Medicine and Community Health, and Internal Medicine and the Institute for Translational Sciences, University of Texas Medical Branch, Galveston (K.E.A.); the Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC (H.L.B.); Royal Gwent Hospital, Newport (A.V.A., C.E.), the Centre for Dermatology, University of Manchester, Salford Royal Hospital, Manchester (L.E.R.), and the Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford (C.R.G.) - all in the United Kingdom; the Department of Medicine, University of California, San Francisco, San Francisco (D.M.B.); the Department of Medicine, University of Alabama, Birmingham (J.B.); the Department of Dermatology, Heinrich Heine University, Duesseldorf, Germany (N.J.N., J.F.); the Department of Internal Medicine, University of Utah, Salt Lake City (C.P., J.D.P.); the Department of Dermatology, Henry Ford Hospital, Detroit (H.W.L., I.H.); Hôpital Louis-Mourier, Hôpitaux Universitaire Paris Nord Val de Seine, Assistance Publique-Hôpitaux de Paris, INSERM Unité 1149, Université Paris Diderot, Colombes, France (J.-C.D.); the Departments of Medicine and Dermatology, University Hospital of Helsinki, Helsinki (R.K.); and the Department of Dermatology, Beaumont Hospital, Dublin (G.M.M.).

The New England Journal of Medicine
|July 2, 2015
PubMed
Summary

Afamelanotide significantly increased pain-free sun exposure and improved quality of life for patients with erythropoietic protoporphyria. This treatment demonstrated a favorable safety profile in clinical trials.

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Area of Science:

  • Dermatology
  • Photomedicine
  • Pharmacology

Background:

  • Erythropoietic protoporphyria (EPP) is a severe photodermatosis causing acute phototoxicity, significant pain, and reduced quality of life.
  • Current management for EPP is limited, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To evaluate the safety and efficacy of afamelanotide, an alpha-melanocyte-stimulating hormone analogue, in managing EPP symptoms.
  • To assess afamelanotide's impact on pain reduction, quality of life, and phototoxicity in EPP patients.

Main Methods:

  • Two multicenter, randomized, double-blind, placebo-controlled trials were conducted in the EU and US.
  • Patients received subcutaneous afamelanotide implants (16 mg) or placebo every 60 days, with efficacy measured by pain-free sun exposure duration and quality of life questionnaires.

Main Results:

  • Afamelanotide significantly increased the duration of pain-free sun exposure in both US (median 69.4 vs. 40.8 hours) and EU (median 6.0 vs. 0.8 hours) studies.
  • The number of phototoxic reactions decreased in the afamelanotide group (77 vs. 146 in EU study).
  • Quality of life scores improved, and adverse events were generally mild and not drug-related.

Conclusions:

  • Afamelanotide demonstrated an acceptable safety profile with a manageable adverse event profile.
  • Afamelanotide therapy effectively increased pain-free sun exposure duration and enhanced quality of life for individuals with erythropoietic protoporphyria.