All five participants in the 5x1011 vg/kg and 11012 vg/kg dose cohorts and seven participants in the 21012 vg/kg dose show an acceptable safety profile, stable and durable factor VIII expression and substantial improvement in annualized bleed rate (ABR) after between two and 3.3 years follow-up

Represents the longest stable expression of FVIII following investigational gene therapy and reinforces the ability of AAV gene therapy targeting hepatocytes to achieve stable and durable FVIII expression

Optimizing the dose and immunomodulatory regimen; Phase 3 dosing expected in 2021

PHILADELPHIA, July 12, 2020 (GLOBE NEWSWIRE) -- Spark Therapeutics, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) and a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today 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 Childrens Hospital of Philadelphia.

Fourteen participants in the Phase 1/2 trial received a single administration of investigational SPK-8011, two at a dose of 5x1011 vg/kg, three at a dose of 11012 vg/kg and nine at a dose of 21012 vg/kg. As of the June 3, 2020 data cutoff, results from the five total participants in the 5x1011 vg/kg and 11012 dose cohorts and seven participants in the 21012 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 21012 dose cohort lost FVIII expression likely due to a capsid-based immune response. The seven other participants in the 21012 dose cohort and the five total participants in the 51011 vg/kg and 11012 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.

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, Ph.D., 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 thelowest effective doseand the optimal immunomodulatory regimen, demonstrates safety, predictability, efficacy, and durability.

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. 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 capabilitiesutilizing suspension cell culture at a scale of nearly 500-litersatcell separationwith a corresponding chromatography purification process, which is the scale required to meet clinical and potential commercial demand for hemophilia A.

About SPK-8011 for hemophilia AInvestigationalSPK-8011, a novel bio-engineered adeno-associated viral (AAV) vector utilizing the AAV-LK03 capsid, also referred to as Spark200, contains a codon-optimized human factor VIII gene under the control of a liver-specific promoter. The Food and Drug Administration (FDA) granted orphan-disease designation and breakthrough therapy designation in the U.S., while the European Commission has granted orphan designation toSPK-8011.

About Roche and Spark Therapeutics gene therapy research in hemophilia AWe believe gene therapy has the potential to revolutionize medicine and improve the lives of patients with genetic and other serious diseases. Pairing Roches long-standing commitment to developing medicines in hemophilia with Spark Therapeutics proven gene therapy expertise brings together the best team of collaborators researching gene therapies in hemophilia A.

It is our aligned objective to develop gene therapies for hemophilia A that, with the lowest effective dose and the optimal immunomodulatory regimen, demonstrate safety, predictability, efficacy, and durability for patients.

About Hemophilia AHemophilia is a rare genetic bleeding disorder that causes the blood to take a long time to clot because of a deficiency in one of several blood clotting factors. People living with hemophilia are at risk of excessive and recurrent bleeding spontaneously and from modest injuries, which have the potential to be life threatening. There are approximately 15,000 people with hemophilia A in the U.S. and 19,000 in the five major European countries. Hemophilia A is about four times as common as hemophilia B. Hemophilia A is characterized by mutations in the factor VIII gene (F8), which lead to deficient blood coagulation and an increased risk of bleeding or hemorrhaging. The current standard of care for hemophilia A requires recurrent intravenous infusions of either plasma-derived or recombinant factor VIII to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with hemophilia.

About Spark Therapeutics AtSpark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challengethe inevitability of genetic diseases,includingblindness, hemophilia, lysosomal storage disorders and neurodegenerative diseases.We currently have four programs in clinical trials.At Spark, a member of the Roche Group, we see the path to a world where no life is limited by genetic disease. For more information, visit http://www.sparktx.com, and follow us on Twitter and LinkedIn.

Media Contact:Kevin Giordanokevin.giordano@sparktx.com(215) 294-9942

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Spark Therapeutics Announces Updated Data on SPK-8011 from Phase 1/2 Clinical Trial in Hemophilia A at ISTH 2020 Virtual Congress - GlobeNewswire