Clinical Data
Based on individual participant history for the year prior to the study, the overall ABR for all 15 participants was reduced by 98 percent (calculated based on data after week four; 97 percent based on data after infusion) to an annual rate of 0.2 bleeds per participant, compared to an annual rate of 8.9 bleeds before SPK-9001 administration. Only one participant experienced a bleeding event four or more weeks after SPK-9001 infusion.Overall AIR was reduced by 99 percent (calculated based on data after week four; also 99 percent based on data after infusion) for all 15 participants to an annual rate of 0.9 infusions, compared to an annual rate of 57.2 infusions before infusion. Six participants received factor IX infusions following SPK-9001 administration: two for reported spontaneous bleeds, two prior to surgery, one at the end of the study (discretionary, per protocol) and one for prophylaxis for a minor traumatic non-bleeding event.As of the May 7, 2018 data cutoff, all 13 participants with at least 12 weeks of follow-up after SPK-9001 infusion, the length of time required to achieve steady-state factor IX activity levels, reached stable factor IX levels of more than 12 percent. The range of steady-state factor IX activity level, beginning at 12 weeks through 52 weeks of follow-up for the first 10 participants infused, was 14.3 to 76.8 percent. For the three participants infused with SPK-9001 manufactured using an enhanced process who reached 12 or more weeks of follow-up, the range of steady-state factor IX activity level was 38.1 to 54.5 percent. The two remaining participants are out 11 and 5 weeks, per the May 7, 2018 data cut-off date.In this open-label, non-randomized and multicenter Phase 1/2 clinical trial, there have been no serious adverse events, no thrombotic events and no factor IX inhibitors developed, and all 15 participants infused with SPK-9001 have discontinued prophylactic clotting factor infusions. Two participants, one having received SPK-9001 manufactured using an enhanced process, reported related adverse events of elevated transaminases and were treated with a tapering course of oral corticosteroids. The events were asymptomatic, and one event has been resolved, as of the May 7, 2018 data cutoff. One additional participant received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.