Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria

Abstract

SummaryBackground In erythropoietic protoporphyria (EPP), an inherited disease of porphyrin-biosynthesis, the accumulation of protoporphyrin in the skin causes severely painful phototoxic reactions. Symptom prevention was impossible until recently when afamelanotide became available. Afamelanotide-induced skin pigmentation has statistically significantly improved light-tolerance, although the clinical significance of the statistical effect was unknown. Objectives To assess clinical effectiveness by recording compliance and safety during prolonged use. Methods We report longitudinal observations of 115 ambulatory patients with EPP, who were treated with a total of 1023 afamelanotide implants over a period of up to 8 years at two porphyria centres; one in Rome, Italy, and the other in Zurich, Switzerland. Results Since the treatment first became available in 2006, the number of patients treated with 16 mg afamelanotide implants rose continuously until June 2014, when 66% of all patients with EPP known to the porphyria centres were treated. Only three patients considered afamelanotide did not meet their expectations for symptom improvement; 23% discontinued the treatment for other, mostly compelling, reasons such as pregnancy or financial restrictions. The quality of life (QoL) scores, measured by an EPP-specific questionnaire, were 31 AE 24% of maximum prior to afamelanotide treatment, rose to 74% after starting afamelanotide and remained at this level during the entire observation period. Only minor adverse events attributable to afamelanotide, predominantly nausea, were recorded. Conclusion Based on the improved QoL scores, high compliance and low discontinuation rates, we conclude that afamelanotide exhibits good clinical effectiveness and good safety in EPP under long-term routine conditions.

Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review

“…One hotspot of current research is afamelanotide, which is a tridecapeptide that simulates human alpha melanocyte stimulating hormone (α-MSH), could bind to the melanocortin 1 receptor of melanocytes and promote the formation of epidermal melanin. Melanin can absorb, disperse, and reduce ultraviolet (UV), scavenging of free radicals, antioxidant, thereby reducing light-induced skin damage and alleviating photosensitive skin pain (Harms et al, 2009;Biolcati et al, 2015;Langendonk, 2015). Langendonk et al (2015) through a randomized, double-blind, multi-center, placebo control trial in the European Union and the United States found that afamelanotide, compared with the placebo, significantly increased the duration of sun exposure without photosensitive pain and improved the quality of life of EPP patients, and side effects are infrequent and acceptable.…”

Porphyrias: A 2015 update

“…Opaque topical sunscreens or UVB phototherapy may improve the tolerance of light. Symptom prevention was impossible until 2006 when afamelanotide (Scenesse ® ), a melanocyte-stimulating hormone analogue that induces epidermal melanin skin-tanning and has an anti-inflammatory effect on the skin [53,54], became available. From 2006 through 2015, the 16 mg afamelanotide implants have shown good clinical effectiveness, with a reduction in patients' sun sensitivity, an improvement in their quality of life quality and, in EPP, good safety with long-term use [54].…”

Protoporphyrin IX: the Good, the Bad, and the Ugly

“…Pharmacological approaches have included pharmaceutical-grade b-carotene, narrow wave UVB phototherapy, cysteine, afamelanotide, antihistamines, and vitamin C (Table 1) (Sawyer et al, 1980;Krook and Haeger-Aronsen, 1982;Mathews-Roth et al, 1994;Collins and Ferguson, 1995;Warren and George, 1998;Wahlin et al, 2011a;Fabrikant et al, 2013;Tintle et al, 2014;Biolcati et al, 2015;Langendonk et al, 2015;Lengweiler et al, 2015;Minder and Schneider-Yin, 2015). Minder et al (2009) reviewed the treatment options for dermal photosensitivity in EPP in 2009 and concluded that the data were insufficient to prove efficacy of any treatments studied in EPP.…”

“…Minder et al (2009) reviewed the treatment options for dermal photosensitivity in EPP in 2009 and concluded that the data were insufficient to prove efficacy of any treatments studied in EPP. Since then, controlled trials have demonstrated improved light tolerance in EPP and XLP with afamelanotide, an a-melanocytestimulating hormone analog that increases skin melanogenesis (Harms et al, 2009;Fabrikant et al, 2013;Biolcati et al, 2015;Langendonk et al, 2015).…”

“…• May potentiate erythema and skin photoaging Collins and Ferguson, 1995 • Psoralen UVA • Decreased photosensitivity and improved quality of life Sawyer et al, 1980;Minder et al, 2009;Fabrikant et al, 2013;Biolcati et al, 2015;Langendonk et al, 2015;Lengweiler et al, 2015;Minder and Schneider-Yin, 2015 • Induces production of eumelanin that serves as a natural filter to reduce all wavelengths of light, quench UV light, and decrease free radicals…”