Spark Therapeutics announced updated preliminary data today from 10 infused participants in the ongoing Phase 1/2 clinical trial of investigational SPK-9001 for hemophilia B. All participants have experienced consistent and sustained increases in factor IX activity following administration of the investigational therapy. These data will be presented at the Hemostasis and Thrombosis Research Society (HTRS) 2017 Scientific Symposium in Scottsdale, Arizona on Friday, April 7, by Adam Cuker, M.D., assistant professor of medicine at the Perelman School of Medicine of the University of Pennsylvania and a clinical investigator at Children’s Hospital of Philadelphia.
Data as of March 24, 2017 will be presented on 10 participants in the study, who were dosed with a single administration of 5 x 1011 vector genomes (vg)/kg body weight. All participants have discontinued routine infusions of factor IX concentrates. Based on individual patient history prior to the study, ABR was reduced by 96 percent to a mean of 0.39 annual bleeds, compared with 9.2 bleeds before SPK-9001 administration. AIR was reduced 99 percent to a mean of 0.98 annual infusions, compared with 68.5 infusions before SPK-9001 administration.
As of the data cutoff, nine of the 10 infused participants have not taken factor IX concentrates to prevent or control bleeding events since vector administration. As previously reported, one participant with severe joint disease has self-administered precautionary infusions for persistent knee pain. The mean steady-state factor IX activity level post 12 weeks treatment for the 10 participants was a sustained 33 percent (range as of the data cutoff: 14 to 81 percent). In the study to date, no serious adverse events have been reported, including no factor IX inhibitors and no thrombotic events. These data represent more than 2,400 cumulative patient days of exposure from the start of the trial.
Two of the 10 participants experienced an asymptomatic, transient elevation in liver enzymes, or decline in FIX activity, potentially indicative of an immune response to the Spark100 vector capsid, that occurred several weeks post infusion. Both participants received a tapering dose of oral corticosteroids, after which their alanine aminotransferase (ALT) levels returned to baseline. The activity level of one of these participants has stabilized at approximately 15 percent for more than nine weeks post corticosteroid use. The other participant had a factor IX activity level between 70 to 80 percent at completion of steroid use.
“The additional preliminary data continue to support our initial observations that a single intravenous administration of SPK-9001 has resulted in consistent and sustained levels of factor IX activity for trial participants,” said Katherine A. High, M.D., president and chief scientific officer at Spark Therapeutics. “Notably, all participants to date have consistently achieved our targeted therapeutic range of FIX activity. As we continue to glean more insights from these preliminary data, our analysis suggests that a tapering course of oral corticosteroids has been well-tolerated and may help control potential capsid immune responses following SPK-9001 infusion.”
Filed Under: Drug Discovery