Spark Therapeutics recently released updated clinical study data on SPK-8011, the company’s investigational gene therapy candidate for hemophilia A.
SPK-8011 is administered via a one-time intravenous infusion, which is designed to elicit the production of therapeutic levels of factor VIII (FVIII), a protein that is normally deficient in individuals with hemophilia A. Spark Therapeutics’ proprietary bioengineered adeno-associated virus (AAV) vectors carry the genetic codes that prompt the FVIII production. The approach being tested in this trial uses a modified novel AAV vector genome (vg) to deliver the corrected FVIII gene into liver cells where the protein is normally generated.
The phase 1/2 trial data was presented by the study’s Principal Investigator Lindsey A. George, MD, of the Perelman School of Medicine, University of Pennsylvania and Children’s Hospital of Philadelphia. George’s presentation was given during the International Society of Thrombosis and Hemostasis Virtual Congress, held July 12-14, 2020.
The 14 participants in the phase 1/2 trial received a single administration of investigational SPK-8011 at one of three dose levels: two at a dose of 5×10 vg/per kilogram body weight (vg/kg), three at a dose of 1×10 vg/kg and nine at a dose of 2×10 vg/kg. As of the June 3, 2020 data cutoff, results from the five total participants in the 5×10 vg/kg and 1×10 dose groups and seven participants in the 2×10 vg/kg group show an “acceptable” safety profile, a 91% reduction in annualized bleed rate, and a 96% reduction in FVIII product infusions.
According to a new Spark press release, two of nine participants in the 2×10 dose group lost FVIII expression, attributed most likely to an immune response. In addition, seven other participants in the 2×10 dose group and five total participants in the 5×10 vg/kg and 1×10 vg/kg dose groups continue to show “stable and durable” factor FVIII expression.
Since previous disclosure of these data, two participants experienced mild and non-serious steroid-associated adverse events (e.g. weight gain, insomnia, adrenal insufficiency and worsening gastroesophageal reflux that resolved with medical intervention). Previously disclosed adverse events include one participant experiencing an acute reaction to the infusion that resolved.
“We are very encouraged by these interim data that continue to show an acceptable safety profile and a substantial reduction in bleeds for more than two years of observation on average, with one participant being observed for more than three years,” said Federico Mingozzi, PhD, chief scientific officer, Spark Therapeutics. “Our focus is on optimizing the dose and immunomodulatory regimen before moving to a Phase 3 clinical study that falls in line with our strategy to progress a hemophilia A gene therapy that, at the lowest effective dose and the optimal immunomodulatory regimen, demonstrates safety, predictability, efficacy, and durability.”
Source: Spark press release dated July 12, 2020