Rare Daily Staff

Interim data from a phase 1/2 study of Spark Therapeutics’ and Pfizer’s experimental gene therapy SPK-9001 for hemophilia B published in the New England Journal of Medicine showed it cut the annualized bleeding rate of patients by 97 percent and reduced the use of factor IX concentrate by 99 percent.

Hemophilia is a rare genetic bleeding disorder that results from a deficiency in one of several blood clotting factors. People with hemophilia are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life threatening. People with severe hemophilia often bleed spontaneously into their muscles or joints, or rarely into other critical closed spaces, such as the intracranial space, where bleeding can be fatal. People with hemophilia B have a deficiency in clotting factor IX, a specific protein in the blood.

The current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant factor IX to control and prevent bleeding episodes. Spark’s SPK-9001 is a gene therapy that delivers a functional gene that then allows the patients body to produce adequate amounts of factor IX.

“People who live with hemophilia today face a lifelong need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said Katherine High, president and head of Research and Development at Spark Therapeutics and co-author of the paper. “The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”

With a cumulative follow-up of 492 weeks of observation of the first 10 adult male participants, the mean steady-state factor IX activity was 34 percent of normal (range of 14-81 percent) following a single administration of investigational SPK-9001.

The annualized bleeding rate in the open-label, non-randomized, multicenter clinical trial fell from a mean rate of 11.1 events per year before vector administration to 0.4 events per year after vector administration.

There were no serious adverse events during or following infusion of SPK-9001, and no participants experienced thrombotic events or developed factor IX inhibitors. Two participants developed an asymptomatic and transient increase in liver enzymes that resolved with a tapering dose of oral corticosteroids. One participant with severe joint disease has administered factor for suspected bleeding, but overall factor use for this participant was 91 percent lower than before SPK-9001 infusion.

Spark and Pfizer entered into a collaboration in December 2014 for the SPK-FIX, which included SPK-9001. Under that agreement, Spark is responsible for conducting all phase 1/2 studies for any product candidates, while Pfizer will assume responsibility for pivotal studies, regulatory activities, and global commercialization of any products that result from the collaboration.

December 7, 2017

Photo: Katherine High, president and head of Research and Development at Spark Therapeutics