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The following is an excerpt from a press release from Spark Therapeutics.


Spark Therapeutics, a member of the Roche Group and a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, announced updated data from three dose cohorts of the ongoing Phase 1/2 clinical trial of investigational SPK-8011 in hemophilia A. These data were presented at the International Society of Thrombosis and Hemostasis (ISTH) 2020 Virtual Congress by Principal Investigator Lindsey A. George, M.D., The Perelman School of Medicine, University of Pennsylvania and Children鈥檚 Hospital of Philadelphia.

Fourteen participants in the Phase 1/2 trial received a single administration of investigational SPK-8011, two at a dose of 5脳1011 vg/kg, three at a dose of 1脳1012 vg/kg and nine at a dose of 2脳1012 vg/kg. As of the June 3, 2020 data cutoff, results from the five total participants in the 5脳1011 vg/kg and 1脳1012 dose cohorts and seven participants in the 2脳1012 vg/kg dose cohort show an acceptable safety profile, 91-percent reduction in annualized bleed rate (ABR), 96-percent reduction in FVIII infusions and stable and durable factor FVIII expression after between two and 3.3 years of follow-up.

As previously disclosed, two of nine participants in the 2脳1012 dose cohort lost FVIII expression likely due to a capsid-based immune response. The seven other participants in the 2脳1012 dose cohort and the five total participants in the 5脳1011 vg/kg and 1脳1012 vg/kg dose cohorts continue to show stable and durable factor FVIII expression. These data represent the longest stable expression of FVIII following investigational gene therapy and reinforce the ability of AAV gene therapy targeting hepatocytes to achieve stable and durable FVIII expression.

鈥淲e 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,鈥 said Federico Mingozzi, Ph.D., chief scientific officer, Spark Therapeutics. 鈥淥ur 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聽lowest effective dose聽and the optimal immunomodulatory regimen, demonstrates safety, predictability, efficacy, and durability.鈥

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. Three participants reported liver function test (LFT) elevations. One of the events was grade two transaminitis, and two were grade one. All three events resolved. 聽One participant was electively admitted to the hospital to receive intravenous steroids. The event subsequently resolved. The admission to the hospital for these infusions met the criteria for a serious adverse event.

Across the Phase 1/2 study and through the data cutoff, all 14 participants demonstrated rapid clearance of vector from semen, serum, saliva and urine within two weeks post-vector administration. The vector was not detectable in peripheral blood mononuclear cells (PBMCs), semen, serum, saliva and urine by six weeks post-vector administration in all participants.

Spark Therapeutics continues optimizing the dose and immunomodulatory regimen for investigational SPK-8011 and SPK-8016, for hemophilia A patients with inhibitors. The Phase 3 run-in study is ongoing, and dosing participants in Phase 3 is expected to occur in 2021.

Additionally, Spark has scaled-up its state-of-the-art gene therapy manufacturing capabilities聽utilizing suspension cell culture at a scale of nearly 500-liters聽at聽cell separation聽with a corresponding chromatography purification process, which is the scale required to meet clinical and potential commercial demand for hemophilia A.

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