{"id":22316,"date":"2022-09-05T04:45:00","date_gmt":"2022-09-04T20:45:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=22316"},"modified":"2022-09-05T06:02:48","modified_gmt":"2022-09-04T22:02:48","slug":"nejm%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9aaavs3%e5%9f%ba%e5%9b%a0%e6%b2%bb%e7%96%97%e4%b9%99%e5%9e%8b%e8%a1%80%e5%8f%8b%e7%97%85%e6%82%a3%e8%80%85%e7%9a%84%e4%b8%b4%e5%ba%8a1%e6%9c%9f","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=22316","title":{"rendered":"[NEJM\u53d1\u8868\u8bba\u6587]\uff1aAAVS3\u57fa\u56e0\u6cbb\u7597\u4e59\u578b\u8840\u53cb\u75c5\u60a3\u8005\u7684\u4e34\u5e8a1\u671f\u548c2\u671f\u8bd5\u9a8c"},"content":{"rendered":"\n

ORIGINAL ARTICLE<\/a><\/p>\n\n\n\n

Phase 1\u20132 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B<\/h1>\n\n\n\n

Pratima Chowdary, Susan Shapiro, Mike Makris,\u00a0et al<\/h3>\n\n\n\n

N Engl J Med 2022; 387:237-247
DOI: 10.1056\/NEJMoa2119913<\/h3>\n\n\n\n

<\/p>\n\n\n\n

Abstract<\/h2>\n\n\n\n

BACKGROUND<\/h2>\n\n\n\n

FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B.<\/p>\n\n\n\n

METHODS<\/h2>\n\n\n\n

In this multicenter, open-label, phase 1\u20132 trial, we assessed the safety and efficacy of varying doses of FLT180a in patients with severe or moderately severe hemophilia B (factor IX level, \u22642% of normal value). All the patients received glucocorticoids with or without tacrolimus for immunosuppression to decrease the risk of vector-related immune responses. After 26 weeks, patients were enrolled in a long-term follow-up study. The primary end points were safety and efficacy, as assessed by factor IX levels at week 26.<\/a><\/p>\n\n\n\n

RESULTS<\/h2>\n\n\n\n

Ten patients received one of four FLT180a doses of vector genomes (vg) per kilogram of body weight: 3.84\u00d71011<\/sup>\u00a0vg, 6.40\u00d71011<\/sup>\u00a0vg, 8.32\u00d71011<\/sup>\u00a0vg, or 1.28\u00d71012<\/sup>vg. After receiving the infusion, all the patients had dose-dependent increases in factor IX levels. At a median follow-up of 27.2 months (range, 19.1 to 42.4), sustained factor IX activity was observed in all the patients except one, who resumed factor IX prophylaxis. As of the data-cutoff date (September 20, 2021), five patients had normal factor IX levels (range, 51 to 78%), three patients had levels from 23 to 43%, and one had a level of 260%. Of the reported adverse events, approximately 10% were related to FLT180a and 24% to immunosuppression. Increases in liver aminotransferase levels were the most common FLT180a-related adverse events. Late increases in aminotransferase levels occurred in patients who had received prolonged tacrolimus beyond the glucocorticoid taper. A serious adverse event of arteriovenous fistula thrombosis occurred in the patient with high factor IX levels.<\/p>\n\n\n\n

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CONCLUSIONS<\/h2>\n\n\n\n

Sustained factor IX levels in the normal range were observed with low doses of FLT180a but necessitated immunosuppression with glucocorticoids with or without tacrolimus. (Funded by Freeline Therapeutics; ClinicalTrials.gov numbers, NCT03369444. opens in new tab<\/a> and NCT03641703. opens in new tab<\/a>; EudraCT numbers, 2017-000852-24. opens in new tab<\/a> and 2017-005080-40. opens in new tab<\/a>.)<\/p>\n","protected":false},"excerpt":{"rendered":"

ORIGINAL ARTICLE Phase 1\u20132 Trial of AAVS3 Gene Therapy […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22316"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=22316"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22316\/revisions"}],"predecessor-version":[{"id":22317,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22316\/revisions\/22317"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=22316"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=22316"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=22316"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}