Spark Therapeutics Announces Updated Data on SPK-8011 from Ongoing Phase 1/2 Dose-escalation Clinical Trial in Hemophilia A at 60th American Society of Hematology (ASH) Annual Meeting and Exposition

Spark Therapeutics (NASDAQ: ONCE), a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today announced updated preliminary data on the first 12 participants in the ongoing Phase 1/2 clinical trial of investigational SPK-8011 in hemophilia A. These data were presented at the 60thAmerican Society of Hematology (ASH) Annual Meeting and Exposition in San Diego by Principal Investigator Lindsey A. George, M.D., assistant professor of pediatrics, The Perelman School of Medicine, University of Pennsylvania and attending physician in the Division of Hematology at Children's Hospital of Philadelphia.

The 12 participants in the Phase 1/2 trial received a single administration of investigational SPK-8011, including two at a dose of 5x1011 vector genomes (vg)/kg body weight, three at a dose of 1x1012 vg/kg and seven at a dose of 2x1012 vg/kg. As of the Nov 2, 2018, data cutoff, no inhibitors, no thrombotic events and no persistent or unresolved transaminase elevations have been observed across a cumulative 9.7 years of data follow-up. Across all three doses, beginning four weeks after vector infusion, there has been a 94-percent reduction in bleeds and a 95-percent reduction in FVIII infusions.

Participants in the 5x1011 vg/kg and 1x1012 vg/kg dose cohorts have shown dramatic reductions in bleeds and infusions as well as stable FVIII activity with up to 78 weeks of follow-up, with observation ongoing.

Among the five participants treated in the 2x1012 vg/kg cohort who did not experience an immune response-associated decline in FVIII expression, beginning four weeks after vector infusion, there has been a 100-percent reduction in bleeds and a greater than 99-percent reduction in FVIII infusions, with up to 46 weeks of follow-up.

"These updated data continue to demonstrate impressive reductions in bleeds and infusions across all doses studied, including complete-elimination of bleeds in the five participants at 2x1012 vg/kg cohort who did not experience a deleterious immune response," said Katherine A. High, M.D., president and head of research and development at Spark Therapeutics. "Moreover, the safety profile has been excellent, with no inhibitors, no prolonged transaminase elevations and no thromboembolic events for the 12 participants. Consistent with our expectations and aligned with prior results using Spark Therapeutics' adeno-associated viral (AAV) technology platform, the participants in the first two dose cohorts have seen durable responses characterized by stable factor VIII activity levels out as long as one and a half years."

Seven of the 12 participants received a tapering course of reactively administered oral steroids, including five in the 2x1012 vg/kg cohort, in response to an alanine aminotransferase (ALT) elevation above the patient's baseline, declining FVIII levels and/or positive IFN-g enzyme-linked immunospots (ELISPOTs). For all participants, steroids led to rapid normalization of ALT and/or ELISPOTs.

All participants responded to vector infusion with an increase in circulating levels of FVIII. As previously disclosed, two participants in the 2x1012 vg/kg cohort had a suspected capsid immune response that caused their FVIII levels to decline to less than 5 percent. One of these participants did not rapidly respond to reactively administered oral steroids and was electively admitted to the hospital to receive two intravenous (IV) methylprednisolone infusions. The event subsequently resolved without sustained deleterious effects other than the decrease in FVIII activity. The admission to hospital for these infusions met the criteria for a serious adverse event (SAE).

Across the study through the data cutoff, the 12 participants demonstrated rapid clearance of vector from body fluids, with median time to clear vector DNA from saliva, semen and urine of two weeks.

"We expect to provide a further update of the Phase 1/2 study in mid-2019, which will include an additional 2x1012 vg/kg dose cohort of five to 10 participants dosed with material from our suspension manufacturing process and will also evaluate a prophylactic - rather than reactive - approach to steroid administration with the goal of reducing or eliminating immune responses," added High.

Spark Therapeutics intends to initiate a Phase 3 run-in study by the end of 2018 to collect prospective observational data on trial participants.