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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Enrollment Characteristics and Real-World Insights Into Disease Burden and Givosiran Treatment in Patients With Acute Hepatic Porphyria in the ELEVATE Registry Eliane Sardh1, David Cassiman2, Laurent Gouya3, Bruce Wang4, Weiming Du5, Desmond Murphy5, Teresa L.Kauf5, Jamie L.Weiss5, Manisha Balwani6. 1Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.2Department of Gastroenterology-Hepatology and Center for Metabolic Diseases, University Hospital Leuven, Leuven, Belgium.3Centre Français des Porphyries, Paris, France.4University of California, San Francisco, CA, USA.5Alnylam Pharmaceuticals, Cambridge, MA, USA.6Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA |
Abstract
Background: Acute hepatic porphyria (AHP) comprises a group of rare genetic disorders that affect the heme biosynthesis pathway. Overproduction and accumulation of heme intermediates δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) lead to acute attacks and chronic complications across multiple organ systems, severely impacting patients’ quality of life. Givosiran, an RNA interference therapeutic, is approved for AHP across the US, EU, UK, Canada, Australia, and several countries in Latin America, the Middle East and Asia-Pacific. ELEVATE (NCT04883905) is an ongoing, international registry designed to characterize the natural history and outcomes of real-world management of patients with AHP, including long-term safety and effectiveness of givosiran. Objectives: To characterize enrollment characteristics and real-world management of patients with AHP in the ELEVATE registry. Methods: ELEVATE was initiated in April 2021 and includes patients aged ≥12 years with AHP. There are 28 active sites across 9 countries in Europe, North America, and Asia. Data from routine clinical assessments are collected for registry patients at least once annually. Results: As of March 24, 2025, 222 patients with AHP (n=184 females; 82.9%) were enrolled in ELEVATE, with more patients in Europe (n=121; 54.5%) than in North America (n=96; 43.2%) or rest of world (n=5; 2. 3%). Median (range) age at consent was 43.0 (12–77) years, with most patients aged 18-45 years (n=113; 50.9%). Most patients were White (n=146; 65.8%), and the median (range) body mass index was 24.3 (15.9-53.1) kg/m2. Median (range) age at diagnosis/testing (based on family history) was 29.0 (0-70) years, and median (range) age at symptom onset among symptomatic patients (n=199; 89.6%) was 29.0 (6-69) years. A majority of patients (n=144; 64.9%) had ≥1 relative with known or suspected AHP. AHP subtype distribution was as follows: acute intermittent porphyria (n=186; 83.8%), variegate porphyria (n=27; 12.2%), hereditary coproporphyria (n=6; 2.7%), and ALA dehydratase-deficiency porphyria (n=1; 0.5%); subtype was unreported for 2 patients (0.9%). Enrollment comorbidities that were reported for >15% of patients included hypertension (n=58; 26.1%), depression (n=44; 19.8%), anxiety (n=52; 23.4%), and other concurrent diseases unrelated to AHP (n=64; 28.8%). Additional medical history included chronic kidney disease (n=34; 15.3%), iron overload (n=22; 9.9%), and liver disease (n=20; 9.0%). Overall, 158 patients (71.2%) reported receiving treatment for AHP, most commonly givosiran (n=144; 64.9%) or hemin prophylaxis (n=61; 27.5%). Other treatments included gonadotropin-releasing hormone agonists (n=1; 0.5%), and other medications (n=11; 5.0%). Conclusions: Enrollment results from patients in the ongoing ELEVATE registry provide insights into patient characteristics and treatment patterns. These results and continued data collection will inform subsequent analyses of the long-term safety and effectiveness of givosiran. These data also underscore the heterogeneous nature of AHP and the substantial burden of comorbidities among affected patients. As hematologists rarely encounter AHP, these findings will help enhance clinical understanding and management of AHP.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.