{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:59:17Z","timestamp":1789498757636,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Messina, Italy","award":["J43C22000500006"],"award-info":[{"award-number":["J43C22000500006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of the orphan drug cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy delivered via intracerebroventricular infusion, has been approved for Neuronal Ceroid Lipofuscinosis type 2 disease. The safety profile of cerliponase alfa has been established based on pre-authorization studies; currently, no post-marketing investigation has been performed to confirm it. Here, a descriptive analysis of real-world spontaneous reporting data of suspected adverse reactions (SARs) to cerliponase alfa in the EudraVigilance database was performed to compile clear information on the safety profile. Methods: Suspected adverse reactions to cerliponase alfa reported in the data system EudraVigilance were analyzed for age, sex of the patient, adverse reactions, and the indication for use. Results: Cases with suspected adverse reactions to cerliponase alfa were found to be more frequent in female patients (58.1%) and in children aged 3\u201311\u2009years. The most common adverse reactions were, in decreasing order, fever\/pyrexia, device-related infection, vomiting, seizures\/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. Conclusions: The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth.<\/jats:p>","DOI":"10.3390\/ph17111513","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"1513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Adverse Reactions to the Orphan Drug Cerliponase Alfa in the Treatment of Neurolipofuscinosis Type 2 (CLN2)"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4075-8065","authenticated-orcid":false,"given":"Ilaria","family":"Ammendolia","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"},{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sframeli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-6387","authenticated-orcid":false,"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7286-5674","authenticated-orcid":false,"given":"Luigi","family":"Cardia","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Noto","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaconcetta","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8116-4821","authenticated-orcid":false,"given":"Gioacchino","family":"Calapai","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"De Pasquale","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mannucci","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Calapai","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"},{"name":"Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1126\/science.2006403","article-title":"Curing the Orphan Drug Act","volume":"251","author":"Thoene","year":"1991","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1080\/14740338.2019.1614165","article-title":"Role of healthcare databases and re gistries for surveillance of orphan drugs in the real-world setting: The italian case study","volume":"18","author":"Crisafulli","year":"2019","journal-title":"Expert Opin. 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