Preliminary data from four participants who received investigational SPK-8016 at a dose of 5X1011 vg/kg and have no history of FVIII inhibitors show no serious adverse events and stable and durable factor VIII (FVIII) expression at greater than 52 weeks
Data show 98-percent reduction in annualized infusion rate (AIR) and 85-percent reduction in annualized bleed rate (ABR) after a follow up of between 15 and 18 months or 5.5 total patient years
SPK-8016 is being investigated in a two-part Phase 1/2 study, with part one designed to evaluate the safety and efficacy in adult males with clinically severe hemophilia A and no measurable inhibitor against FVIII
PHILADELPHIA, February 5, 2021 (GLOBE NEWSWIRE) — Spark Therapeutics, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) and a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today announced preliminary data from part one of the ongoing Phase 1/2 open-label, non-randomized, dose-finding study of the investigational SPK-8016 in hemophilia A. Part one of the Phase 1/2 study is designed to evaluate the safety and efficacy of SPK-8016 in adult males with clinically severe hemophilia A and no measurable inhibitor against FVIII. These data were presented at the European Association for Haemophilia and Allied Disorders (EAHAD) 2021 Virtual Congress by investigator Spencer Sullivan, M.D., Mississippi Center for Advanced Medicine.
All four participants who have hemophilia A and no history of FVIII inhibitors received a single intravenous administration of SPK-8016 at a dose of 5X1011 vg/kg. As of the October 26, 2020 data cutoff, participants have stable and durable factor VIII (FVIII) activity at greater than 52 weeks ranging from 5.9-percent to 21.8-percent with no serious adverse events (AEs), and no FVIII inhibitor development. Data show a 98-percent reduction in annualized infusion rate (AIR) and 85-percent reduction in annualized bleed rate (ABR) after a follow up of between 15 and 18 months or 5.5 total patient years.
“Preliminary data from part one of the Phase 1/2 study of SPK-8016, on four participants who have no history of FVIII inhibitors, are very encouraging as we observe stable and durable FVIII activity with a safety profile supporting further evaluation at a very low vector dose,” said Gallia Levy, M.D., Ph.D., chief medical officer, Spark Therapeutics. “We are critically evaluating these data to plan the second part of the SPK-8016 study.”
One of four participants did not receive immunomodulatory agents and demonstrated the highest level of FVIII activity (21.8-percent at greater than 52 weeks). Three of four participants received oral corticosteroid therapy, which was initiated between three- and six-weeks following vector infusion upon clinical suspicion of a hepatocyte-directed immune response. Daily oral corticosteroid therapy was administered in tapering doses for a range of 43 and 48 weeks. Two participants received azathioprine and/or tacrolimus as steroid-sparing immune-modulating co-therapy to limit total exposure to prednisone.
No participant demonstrated persistent liver enzyme (alanine aminotransferase [ALT]/aspartate transaminase [AST]) elevations outside of the normal range, with the exception of transaminitis associated with azathioprine toxicity in one participant that resolved as expected after azathioprine was discontinued. No serious AEs were observed. The three participants who received immunomodulatory agents experienced mild-to-moderate, non-serious steroid-associated AEs.
About SPK-8016 for hemophilia A
Investigational SPK-8016 is a novel, internally developed gene therapy for hemophilia A to address the unmet medical need within the hemophilia A inhibitor patient community. Inhibitors occur in as many as 30 percent of people with severe or moderately severe hemophilia A. Spark retains global commercialization rights to SPK-8016.
About Roche and Spark Therapeutics gene therapy research in hemophilia A
We believe gene therapy has the potential to revolutionize medicine and improve the lives of patients with genetic and other serious diseases. Pairing Roche’s long-standing commitment to developing medicines in hemophilia with Spark Therapeutics’ proven gene therapy expertise brings together the best team of collaborators researching gene therapies in hemophilia A.
It is our aligned objective to develop gene therapies for hemophilia A that, with the lowest effective dose and the optimal immunomodulatory regimen, demonstrate safety, predictability, efficacy, and durability for patients.
About Hemophilia A
Hemophilia is a rare genetic bleeding disorder that causes the blood to take a long time to clot because of a deficiency in one of several blood clotting factors. People living with hemophilia are at risk of excessive and recurrent bleeding spontaneously and from modest injuries, which have the potential to be life threatening. There are approximately 15,000 people with hemophilia A in the U.S. and 19,000 in the five major European countries. Hemophilia A is about four times as common as hemophilia B. Hemophilia A is characterized by mutations in the factor VIII gene (F8), which lead to deficient blood coagulation and an increased risk of bleeding or hemorrhaging. The current standard of care for hemophilia A requires recurrent intravenous infusions of either plasma-derived or recombinant factor VIII to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with hemophilia.
About Spark Therapeutics
At Spark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challenge the inevitability of genetic diseases, including blindness, hemophilia, lysosomal storage disorders and neurodegenerative diseases. We currently have four programs in clinical trials. At Spark, a member of the Roche Group, we see the path to a world where no life is limited by genetic disease. For more information, visit www.sparktx.com, and follow us on Twitter and LinkedIn.