Gene therapy found promising in patients with hemophilia B

A one-time intravenous infusion of a single-stranded recombinant adeno-associated viral vector is safe and results in a sustained level of factor IX coagulant activity, according to results of a recent phase 1-2a study including 10 men with hemophilia B.

The treatment, known as SPK-9001, prevented bleeding and virtually eliminated the need for exogenous factors, said authors of the study, published online Dec. 6 in the New England Journal of Medicine.

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The 10 men enrolled in the study had factor IX coagulation activity 2% or less of normal value. Within a week of treatment with SPK-9001, patients exhibited vector-derived factor IX coagulant activity, according to Dr. George and her colleagues.

For all participants, the mean vector-derived factor IX coagulant activity was 33.7% of normal value, they noted in the report.

Moreover, the bleeding rate was significantly reduced over follow-up, which ranged from 28 to 78 weeks. Annualized bleeding rate was 11.1 events per year before treatment and 0.4 events per year afterward (P = .02), with 9 of 10 patients experiencing no bleeds over the follow-up period, they reported.

Factor use also dropped substantially, from a mean dose of 2,908 IU/kg before vector administration to 49.3 IU/kg afterward, the researchers said, noting that 8 of 10 patients used no factor at all.

No serious adverse events were observed during vector infusion or afterward, but the long-term safety of adeno-associated viral gene transfer will require further study, the researchers said. “However, to date, no genotoxic or gene-silencing events have been noted in human participants, including those who have been followed since the first [adeno-associated virus] trials were reported in 1998,” Dr. George and her colleagues wrote.

Spark Therapeutics and Pfizer funded the study. Dr. George reported support from Spark Therapeutics for the study, and personal fees from Pfizer outside the submitted work. Some of the authors are employees of Spark or had other financial relationships with Spark and/or Pfizer.