Kenny Walter is an editor with HCPLive. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with R&D Magazine. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.
The 1 patient who did not received immunomodulatory agents demonstrated the highest level of FVIII activity.
Spark Therapeutics announced the preliminary data from part 1 of an ongoing phase ½ open-label, non-randomized, dose-finding trial designed to evaluate the safety and efficacy of SPK-8016 in adult males with clinically severe hemophilia A and no measurable inhibitor against FVIII.
The preliminary data, presented European Association for Hemophilia and Allied Disorders (EAHAD) 2021 Virtual Congress, comes from 4 participants who received a single intravenous administration of SPK-8016 at a dose of 5X1011 vg/kg.
At the data cutoff, October 26, the patients have stable and durable FVIII activity at greater than 52 weeks ranging from 5.9-21.8% after treatment with the novel, internally developed gene therapy. There were also no reported serious adverse events reported, as well as no FVIII inhibitor development. Three participants experienced mild-to-moderate, non-serious steroid-associated adverse events following immunomodulatory agents.
The data shows a 98% reduction in annualized infusion rate (AIR) and a 85% reduction in annualized bleed rate (ABR) after a follow-up of 15-18 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, MD, PhD, chief medical officer, Spark Therapeutics, in a statement. “We are critically evaluating these data to plan the second part of the SPK-8016 study.”
Differences in Treatment
Of the 4 patients, 1 individual did not receive immunomodulatory agents and demonstrated the highest level of FVIII activity (21.8% at greater than 52 weeks). In addition, 3 patients received corticosteroid therapy, which was initiated between 3-6 weeks following vector infusion after clinical suspicion of a hepatocyte-directed immune response.
The investigators administered the daily oral corticosteroid therapy in tapering doses for a range of 43-48 weeks and 2 participants received azathioprine and/or tacrolimus as steroid-sparing immune-modulating co-therapy to limit total exposure to prednisone.
None of the participants demonstrated persistent liver enzyme (alanine aminotransferase [ALT]/aspartate transaminase [AST]) elevations outside of what is considered the normal range, with the exception of transaminitis associated with azathioprine toxicity in 1 individual that resolved as expected following discontinuation of azathioprine.