Among patients with hemophilia B, treatment with a gene therapy, FLT180a (verbrinacogene setparvovec), may improve factor IX (FIX) levels, although immunosuppression may be necessary, according to research published in The New England Journal of Medicine.

Hemophilia B, an X-linked heritable disorder, is defined by mutations in the gene encoding for FIX, which leads to insufficient protein production and consequent bleeding events. Patient with less than 1% of normal FIX levels are classified has having severe hemophilia B, which is treated throughout a patient’s life with prophylactic FIX infusions.

This treatment strategy is, however, linked with financial toxicity — and moreover may not prevent all problems associated with hemophilia B. Genetic therapies relying on adeno-associated viruses (AAVs) have previously shown promise in this setting; for this phase 1-2 study ( Identifier: NCT03369444), researchers evaluated the safety and efficacy of FLT180a, an AAV gene therapy designed to treat hemophilia B.

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Overall, 10 patients were enrolled to this trial and received FLT180a, the doses of which were defined per kilogram of body weight. The age range was 25 to 67 years in the cohort; all patients but 1 were White.

The median follow-up was 27.2 months. Analysis showed that all patients had dose-dependent improvements in FIX levels; these were sustained in all patients but 1, who resumed FIX prophylactic therapy. Several patients, furthermore, initiated immunosuppression during treatment.

At data cutoff, normal FIX levels were noted in 5 patients, while 3 had FIX levels of 23%-43% of normal, and 1 patient had 260% the normal FIX level.

The most common adverse event related to therapy was increases in liver aminotransferase levels; 24% of adverse events were due to immunosuppression. The patient with abnormally high FIX levels, furthermore, had a serious arteriovenous fistula thrombosis event.

“Our trial results support further evaluation of FLT180a in clinical trials to confirm the dose and immunosuppressive regimen that are necessary for the maintenance of adequate hemostasis in patients with hemophilia B,” the authors wrote.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Chowdary P, Shapiro S, Makris M, et al. Phase 1-2 trial of AAVS3 gene therapy in patients with hemophilia B. N Engl J Med. 2022;387(3):237-247. doi:10.1056/NEJMoa2119913