A new gene therapy (BBM-H901) developed for patients with hemophilia B effectively reduced the number of bleeds and the need for repeated factor IX (FIX) enzyme replacement therapy without causing serious adverse events, according to findings published in The Lancet Haematology.

BBM-H901 is a novel, molecularly engineered, adeno-associated virus vector gene replacement therapy that targets liver cells through a synthesized liver-specific promotor. The viral vector infects liver cells with the correct coding sequence required for the body to produce functional Padua FIX proteins.

Researchers conducted a single-center, pilot trial in China between October 16, 2019, and January 13, 2021, to assess the safety and efficacy of this novel gene therapy. They enrolled 10 male patients with moderate to severe hemophilia B over the age of 18 years whose baseline FIX protein coagulation activity (FIX:C) was less than 2 IU/dL, along with other strict inclusion criteria.


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After 1 week of daily prophylactic oral prednisone, the patients received an hour-long intravenous infusion of 5×1012 vector genomes per kilogram of bodyweight of BBM-H901. Prednisone use and tapering continued following vector infusion, lasting 8 to 10 weeks in total. Glucocorticoid use reduced the number of cytotoxic T cells and antigen-presenting cells while preventing excessive transaminase elevation.

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Patients were followed up for a median of 58 weeks, during which the researchers obtained blood samples, conducted physical examinations, and assessed adverse events. Two grade 1 or 2 adverse responses associated with the gene therapy occurred, including pyrexia and elevated aminotransferase. No serious grade 3 or 4 adverse events occurred.

FIX:C increased to a mean of 36.9±20.5 IU/dL after 58 weeks. It increased to 57.1±20.2 IU/dL within a week following vector infusion and peaked at 64.1±22.5 IU/dL after 5 weeks. Clinically, BBM-H901 significantly reduced the median annualized bleeding rate from 12 times to 0 (P =.0092). The median number of target joint bleeds for all patients prior to gene therapy was 1.5, subsequently decreasing to 0 following treatment (P =.0031).

Following gene therapy, FIX concentrate replacements continued as needed; however, the median need for FIX concentrate replacement infusions decreased from 53.5 times to 0 (P <.0001).

“BBM-H901 is safe and active in patients with hemophilia B,” the authors concluded. “This regimen of prophylactic administration of glucocorticoid could be useful in blunting the immune responses in other gene therapies in haemophilia patients.”

References

Xue F, Li H, Wu X, et al. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. Published online May 19, 2022. doi:10.1016/S2352-3026(22)00113-2

Clinical trial results of Belief BioMed’s hemophilia B gene therapy drug candidate BBM-H901 published in The Lancet Haematology. News release. Belief Biomed Inc; May 19, 2022.