Spark Therapeutics announced preliminary data from part one of their ongoing phase 1/2 open-label, non-randomized, dose-finding study of SPK-8016, the company’s investigational gene therapy for hemophilia A. Part one 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.
According to a new Spark press release, four participants with hemophilia A and no history of FVIII inhibitors received a single intravenous administration of SPK-8016 at the same dose. As of the October 26, 2020 data cutoff, these participants exhibited “stable and durable” factor VIII (FVIII) activity at greater than 52 weeks, ranging from 5.9% to 21.8% with no serious adverse events (AEs), and no FVIII inhibitor development. The data also shows a 98% reduction in annualized infusion rate and an 85% reduction in annualized bleed rate after a follow up of between 15 and 18 months or 5.5 total patient years.
One of four participants did not receive an immunomodulatory agent to modify their immune response, and subsequently demonstrated the highest level of FVIII activity (21.8% at greater than 52 weeks). Three of the four participants did receive an oral corticosteroid therapy, initiated between three- and six-weeks following infusion of the therapy, in light of “clinical suspicion” of an immune response directed by liver cells. Two participants were also administered additional, nonsteroidal/immune modulating therapies.
Investigators also reported that none of the participants demonstrated persistent liver enzyme elevations outside of the normal range, with one exception which was resolved after the patient discontinued use of a nonsteroidal/immune modulating therapy. Further, no AEs were observed.
“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. “We are critically evaluating these data to plan the second part of the SPK-8016 study.
These data were presented at the recent European Association for Haemophilia and Allied Disorders 2021 Virtual Congress, February 3-5, 2021.
Source: Spark press release dated February 5, 2021