Five years after a single infusion, most men treated with etranacogene dezaparvovec in the HOPE-B trial still had near-normal factor IX activity and few bleeds, according to a report by investigators at the International Society on Thrombosis and Haemostasis (ISTH) 2026 Congress in Paris, France.<\/p>\n
The gene therapy uses an adeno-associated virus serotype 5 (AAV5) vector to carry the hyperactive factor IX Padua variant and is given once at 2 \u00d7 10\u00b9\u00b3 genome copies\/kg. The HOPE-B trial enrolled adult men with severe or moderately severe hemophilia B, defined as a factor IX level at or below 2 IU\/dL. The trial met its primary end point years ago. This post hoc analysis covered the end-of-study data and looked specifically at responders, the patients who expressed transgene-derived factor IX and were able to discontinue prophylaxis.<\/p>\n
Of the 54 men enrolled, 52 responded and 50 completed all 5 years of the study. Endogenous factor IX activity held steady over that span, from a mean level of 39.0 IU\/dL at month 6 to a level of 36.1 IU\/dL at year 5.<\/p>\n
Bleeding rates fell and stayed down. Measured against each patient\u2019s own lead-in period during prophylaxis, adjusted annualized bleeding rates over months 7 to 60 dropped 82% overall, from 3.99 to 0.71. Joint bleeds fell 90%, from 2.20 to 0.23. Reductions in factor IX\u2013treated, spontaneous, and traumatic bleeds came to 87%, 86%, and 82%, respectively. All were significant at P<0.0001.<\/p>\n
Exogenous factor IX use fell 98%. Responders used 262,077 IU a year during lead-in and 5,919 IU a year afterward.<\/p>\n
Two patients did not respond. One had by far the highest baseline AAV5- neutralizing antibody titer in the cohort, 3,212.3. The other received only about 10% of the intended dose after an infusion-related reaction. Among responders, neutralizing antibody titers ranged from below 7 to 678. That range points to a practical question for clinicians weighing the therapy: how much preexisting AAV5 immunity is too much before a patient should be ruled out?<\/p>\n
The effect was not permanent in every case. One responder returned to a regimen of continuous prophylaxis at about 29 months.<\/p>\n
No serious treatment-related adverse events were reported across the 5 years, and there were no cases of oncogenicity or late hepatotoxicity. Two patients died, both from causes unrelated to treatment.<\/p>\n
The authors concluded that treatment with etranacogene dezaparvovec led to sustained endogenous factor IX activity at a nearly normal level, less frequent bleeding, and reduced use of factor IX during 5 years after infusion in responders. They also note that the safety profile was favorable.<\/p>\n","protected":false},"excerpt":{"rendered":"Five years after a single infusion, most men treated with etranacogene dezaparvovec in the HOPE-B trial still had…\n","protected":false},"author":2,"featured_media":224225,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[103,61,60],"class_list":["post-544190","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-ie","tag-ireland"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/544190","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=544190"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/544190\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/224225"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=544190"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=544190"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=544190"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}