{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:54:53Z","timestamp":1790654093803,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T00:00:00Z","timestamp":1742688000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Healthcare Insurers of the Netherlands"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and hypothesis<\/jats:title>\n                    <jats:p>In search for controlled access to expensive innovative orphan drugs, a national access route called \u2018Orphan Drug Access Protocol\u2019 (ODAP) was developed and piloted with lumasiran, a new drug for patients with primary hyperoxaluria type 1 (PH1). Here, we present a 2-year evaluation of this pilot study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Specialists from the Dutch PH1 Expert Centre and the national ODAP steering group developed a protocol for controlled and conditional treatment of children and adults with PH1 with lumasiran. Indication for treatment is based on specific clinical characteristics. Cessation or continuation of therapy is evaluated every 6\u00a0months for 5\u00a0years by a national indication committee consisting of PH1 specialists, based on biochemical and clinical response. Drug wastage is minimized by centralizing and pooling patients for administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between September 2022 and September 2024, 21 PH1 patients were reviewed and 76% were deemed eligible for lumasiran treatment. Ten patients were already receiving lumasiran through clinical trials or early access programs at time of assessment. The follow-up time with lumasiran was 0.1\u20136.6\u00a0years, including trial years. All patients with &amp;gt;1\u00a0year lumasiran treatment responded significantly biochemically and clinically. Details on outcomes are presented. Denials for lumasiran therapy were nearly all based on full pyridoxine responsiveness. All denied patients, except one, had good clinical outcomes. This patient received lumasiran after initial denial based on clinical and biochemical course. Patient selection and minimizing wastage saved approximately \u20ac3\u2009227\u2009065 per year based on the official list price.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This national ODAP protocol enabled access to lumasiran therapy for severely ill patients, prevented unnecessary treatment in others, and provided new insights into the real-world effectiveness of lumasiran in PH1 patients through systematic monitoring. It may serve as a template for future access routes to new expensive therapeutics in orphan diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf060","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T07:09:52Z","timestamp":1742713792000},"page":"1887-1896","source":"Crossref","is-referenced-by-count":7,"title":["Controlled access to lumasiran in primary hyperoxaluria type 1: evaluation of a new access route for orphan drugs in the Netherlands"],"prefix":"10.1093","volume":"40","author":[{"given":"Lisa J","family":"Deesker","sequence":"first","affiliation":[{"name":"Emma Children's Hospital, Amsterdam UMC, University of Amsterdam Department of Pediatric Nephrology, , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper F M","family":"Franssen","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, University of Groningen Department of Nephrology, , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiske","family":"Dorresteijn","sequence":"additional","affiliation":[{"name":"Sophia Children's Hospital, Erasmus Medical Center Department of Pediatric Nephrology, , Rotterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole C A J","family":"van de Kar","sequence":"additional","affiliation":[{"name":"Radboud Institute for Molecular Life Sciences Radboud University Medical Center, Amalia Children's Hospital, , Department of Pediatric Nephrology, Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Azam","family":"Nurmohamed","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center Department of Nephrology, , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Severs","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplantation, Erasmus Medical Center Department of Internal Medicine, , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander F","family":"Garrelfs","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital, Amsterdam UMC, University of Amsterdam Department of Pediatric Nephrology, , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke A M G","family":"Pisters-van Roy","sequence":"additional","affiliation":[{"name":"CZ Healthcare Insurance Department Medical Policy and Advice, ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla E M","family":"Hollak","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location University of Amsterdam Department of Endocrinology and Metabolism, , Amsterdam ,","place":["The Netherlands"]},{"name":"Platform at Amsterdam UMC location University of Amsterdam Medicines for Society, , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap W","family":"Groothoff","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital, Amsterdam UMC, University of Amsterdam Department of Pediatric Nephrology, , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,22]]},"reference":[{"key":"2025092904570516700_bib1","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1056\/NEJMoa2021712","article-title":"Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1","volume":"384","author":"Garrelfs","year":"2021","journal-title":"N Engl J 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