GOTHENBURG, Sweden - A resorbable subcutaneous implant of afamelanotide significantly reduced painful phototoxic attacks in patients with erythropoietic protoporphyria in a year-long multinational clinical trial.
Afamelanotide, a first-in-class investigational chemical analog of alpha-melanocyte-stimulating hormone, is a melanocortin-1 agonist that activates melanocytes and increases melanin levels in the skin.
Treatment with the controlled-release afamelanotide implants was life changing for study participants, Dr. Elisabeth I. Minder noted at the annual congress of the European Academy of Dermatology and Venereology.
Photo: (C) 2009 Lecha et al.; licensee BioMed Central Ltd. (Creative Commons)
Acute photosensitivity reaction in EPP.
"You have to understand that EPP [erythropoietic protoporphyria] patients are conditioned early in life that sunlight is harmful: no exposure to sunlight, no painful attacks. Afamelanotide, compared to placebo, not only reduced phototoxic attacks, it also enabled patients to spend significantly more time outdoors. Anecdotally, patients were quite excited to explore new activities which were never possible in their lives previously," explained Dr. Minder of Triemli Hospital, Zurich.
EPP is a rare inherited disease characterized by severely painful, often intolerable phototoxic attacks lasting for days. An estimated 10,000 individuals are affected worldwide she said.
The afamelanotide implant (Scenesse) is also in clinical trials for more common diseases, including vitiligo, solar urticaria, and polymorphous light eruption, as well as for prevention of actinic keratoses and squamous cell carcinomas in organ transplant recipients.
©Clinuvelt
The afamelanotide implant (above) was found to last up to 60 days.
The European phase III EPP trial involved 100 affected patients who were randomized double blind to a year's worth of alternating treatment cycles consisting of a subcutaneous implant of 16 mg of afamelanotide lasting for 60 days followed by 60 days of a placebo implant.
A total of 91 patients completed the study. The low dropout rate was testimony to how grateful participants were to finally have access to an affective therapy for their disorder, even if for only half of the study period, Dr. Minder said.
Daily pain diaries demonstrated that patients experienced significantly fewer days of severe, moderate, and mild pain during the periods in which they were being treated with afamelanotide. For example, patients spent one-third fewer days in severe pain and less than half as many days in moderate pain during the afamelanotide phase, compared with the placebo phase.
During the active-treatment periods, patients reported spending significantly more time outdoors exposed to the sun. More than half of patients reported spending greater than 6 hours per day outdoors while they were on afamelanotide, something that was unthinkable at baseline.
Only two adverse events were more frequent during active treatment: nausea, which occurred 1-2 days post-implant in 33% of patients when being treated with afamelanotide, compared with 18% of patients when being treated with placebo; and hot flushes, which were noted 1-2 days after afamelanotide implantation in 11% of patients, compared with just 1% with placebo.
Session chair Dr. Maurice Van Steensel of Maastricht (the Netherlands) University commented that a truly double-blind study is impossible with afamelanotide because the alpha-melanocyte-stimulating hormone analog causes tanning. For this very reason, he added, the tanning industry may be interested in this agent as a sunless tanning product.
The U.S. Food and Drug Administration announced in March that Clinuvel (afamelanotide’s manufacturer), could move forward with plans to conduct a phase II clinical trial for treating EPP patients. The confirmatory study is currently enrolling participants. The FDA also granted orphan drug status for the treatment for solar urticaria in late 2009.
In an earlier open-label pilot study, Dr. Minder and her associates showed that treatment with afamelanotide increased tolerance to exposure to artificial light under controlled conditions by 11-fold (N. Engl. J. Med. 2009;360:306-7).
The study was sponsored by Clinuvel Pharmaceuticals. Dr. Minder declared having no financial conflicts.