Evaluation of the immunogenicity of the synthetic α-melanocyte-stimulating hormone (α-MSH) analogue afamelanotide ([Nle4-D-Phe7]-α-MSH, Scenesse®) in erythropoietic protoporphyria patients by ELISA detecting both anti-afamelanotide and anti-α-MSH antibodies.

Abstract

UNLABELLED:

Afamelanotide is an α-melanocyte-stimulating hormone (α-MSH) agonist with proven efficacy in photodermatoses such as erythropoietic protoporphyria (EPP). This peptide drug, repeatedly administered over prolonged time, may induce anti-drug antibodies (ADA). Here, we describe a new ELISA method developed to monitor the occurrence of ADA against afamelanotide as well as against α-MSH. Covalent binding instead of absorption of antigen onto the microtitre wells prevented antigen leakage and enabled extensive washings followed by lower background. The cut-off between antibody-negative and -positive sera was determined. Inhibition of the antigen-antibody reaction by excess soluble antigen tested for specificity. The sensitivity of the ELISA was 608 and 1,390 ng/ml of specific ADA against afamelanotide and α-MSH, respectively. This ELISA method enabled us to investigate the occurrence of ADA during long-term administration of afamelanotide. No immunoreactivity was found in 23 of the 26 EPP patients exposed to the drug for up to 6 years. Pre-existing immunoreactivity against afamelanotide as well as α-MSH was found in 3 patients, whose titres did not change during afamelanotide administration.

CONCLUSION:

The new ELISA is suitable to determine ADA against afamelanotide and α-MSH. Afamelanotide did not elicit ADA during long-term administration in patients with EPP.

• Authors: Stephan Lengweiler, Saskia Kreim, Jasmin Barman-Aksözen, Marcus Maurer, Elisabeth I Minder
• Journal: Skin pharmacology and physiology (Skin Pharmacol Physiol) Vol. 28 Issue 2 Pg. 103-13 ( 2015) ISSN: 1660-5535 [Electronic] Switzerland
• PMID: 25402764 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Antibodies
• Drug Implants
• alpha-MSH
• afamelanotide

Topics

• Antibodies (blood)
• Compassionate Use Trials
• Drug Implants
• Enzyme-Linked Immunosorbent Assay
• Humans
• Porphyria, Erythropoietic (blood, drug therapy, immunology)
• Predictive Value of Tests
• Time Factors
• Treatment Outcome
• alpha-MSH (administration & dosage, analogs & derivatives, immunology, therapeutic use)