Presentation Details
| Emicizumab Prophylaxis in People with Hemophilia A: Summary of 10 Years of Safety Data on Thromboembolic Events and Thrombotic Microangiopathy Katayon Sarouei1, Simona Barlera2, Letizia Polito3, Guillermo Tobaruela3, Juliana M.L Biondo1. 1Genentech, Inc., South San Francisco, CA, USA.2Parexel International, Milan, Italy.3F.Hoffmann-La Roche Ltd, Basel, Switzerland |
Abstract
Background: The HAVEN 1 Phase 3 trial outlined thromboembolic events (TEs) and thrombotic microangiopathies (TMAs) as risks in people with congenital hemophilia A (PwcHA) when taking emicizumab with activated prothrombin complex concentrate (aPCC) at >100U/kg/24h for ≥24h. Objectives: We report updated safety data on emicizumab prophylaxis in PwcHA, as >24,000 people have now received post-market emicizumab (as of Jul 18, 2023; Roche, data on file). Methods: Emicizumab safety reports from clinical trials, registries, expanded access, compassionate use and spontaneous post-marketing reports were analyzed for TEs/TMAs. TEs were identified using the Medical Dictionary for Regulatory Activities (MedDRA v26.0) search strategy: ‘Embolic and Thrombotic Events’ Standardised Medical Query (Broad). TMAs were defined as MedDRA preferred terms: hemolytic uremic syndrome, microangiopathic hemolytic anemia, microangiopathy, TMA, thrombotic thrombocytopenic purpura and renal-limited TMA. Results: As of Aug 01, 2023, 155 total events meeting TE/TMA criteria were found from 24 countries in the Roche Global Safety Database; 97 were in PwcHA, including 34 since the previous analysis (15-May-2022). Two TEs and the five TMAs were related to aPCC (>100U/kg/24h for ≥24h); 90 TEs were not. The new TMA since last analysis was due to aPCC exceeding dose guidelines to treat diverticular hemorrhage in a patient with severe HA who then recovered. In 81 non-aPCC- and non-device-related TEs, median (range) age at event was 48 (0.8–84) years; 55 (67.9%) TEs were related to ≥1 cardiovascular/thrombosis-related risk factor and 26 (32.1%) reported insufficient information. Eleven (13.6%) of the 81 TEs and two (40%) of the five TMAs led to emicizumab discontinuation. Five (6.2%) TEs were fatal: two myocardial infarctions and one cerebrovascular event in three people with multiple risk factors, and two disseminated intravascular coagulation events related to pneumonia in two people >70 years old. Conclusions: No new safety concerns were observed since the last data cut-off and the benefit–risk profile remains positive. Health authorities no longer require special expedited safety reporting of TE/TMAs for emicizumab; however, monitoring and reporting of safety data are ongoing, with no new safety signals with increased patient emicizumab exposure found to date.
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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.