Preliminary SPK-8016 Data Shows Promise Treating Hemophilia A

Gallia Levy, MD, PhD

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.

New Data

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.