Spark Therapeutics’ SPK-8011 Suggests Stable and Durable Factor VIII Expression in Largest Phase 1/2 Gene Therapy Study in Hemophilia A to Date

Factor VIII (FVIII) expression was sustained in 16 of 18 participants with up to 4 years of follow-up to the administration of SPK-8011

Across all dose cohorts, there was a 91.2% reduction in annual bleeding rate (ABR) postSPK-8011 administration and a 97% reduction in annual infusion rate (AIR)

Data to be shared as an oral presentation during the International Society of Thrombosis and Hemostasis (ISTH) 2021 Virtual Congress

PHILADELPHIA, July 21, 2021 — 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 the ongoing Phase 1/2 clinical trial of investigational SPK-8011 in hemophilia A during the International Society of Thrombosis and Hemostasis (ISTH) 2021 Virtual Congress (July 17-21). The data will be shared as an oral presentation today, July 21 at 10:12 a.m. EST. (Abstract OC 67.2)

These data, presented by Principal Investigator Lindsey A. George, M.D., The Perelman School of Medicine, University of Pennsylvania and Children’s Hospital of Philadelphia, demonstrated that administration of SPK-8011 in patients with hemophilia A resulted in sustained factor VIII (FVIII) expression in 16 of 18 participants with up to 4 years of follow-up, as of the May 3, 2021 data cutoff.

“We are encouraged by the results from the phase 1/2 trial for investigational SPK-8011, which has been evaluated in the largest phase 1/2 gene therapy trial in this disease to date, and demonstrates continued response over time, a critical measure of a therapy’s potential to transform lives for people living with this chronic condition,” said Gallia Levy, M.D., Ph.D., Chief Medical Officer, Spark Therapeutics. “We remain focused on optimizing the dose and immunomodulatory regimen in the phase 1/2 study and look forward to continuing our evaluation of this therapy in a Phase 3 study.”

Eighteen participants in the Phase 1/2 trial received a single administration of investigational SPK-8011 in four dose cohorts, ranging from 5×1011 vg/kg to 2×1012 vg/kg. In the 16 patients with sustained FVIII expression, there was a 91.2% reduction in annualized bleed rate (ABR) and 97% reduction in annualized FVIII infusion rate (AIR) after vector administration.

Administration of SPK-8011 in patients with hemophilia A resulted in an acceptable safety profile with no deaths and no FVIII inhibitor development with up to 4 years of follow-up. As previously disclosed, two of the 17 participants with over one year of data lost FVIII expression due to a presumed cellular immune response to the AAV capsid that was unresponsive to immunosuppression. Seven participants reported transient, asymptomatic liver function test (LFT) elevations. All LFT elevations were mild or moderate and have resolved. One participant experienced a mild to moderate acute infusion reaction, which presented as four nonserious adverse events (AEs) (pyrexia, myalgia, vomiting, and back pain) and were resolved. One participant experienced Grade 2 transaminitis, which resulted in elective hospitalization for IV steroid administration, qualifying as a serious AE. The event was subsequently resolved.

These data reinforce the ability of AAV gene therapy targeting hepatocytes to achieve stable and durable FVIII expression with an acceptable safety profile.

About SPK-8011 for hemophilia A
Investigational SPK-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 to SPK-8011.

About Roche and Spark Therapeutics gene therapy research in hemophilia A
We believe gene therapy has the potential to revolutionize medicine and improve the lives of patients with genetic and other serious diseases. Pairing Roche’s 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 A
Hemophilia 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 (FVIII), 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
At Spark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challenge the inevitability of genetic diseases, including blindness, 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, and follow us on Twitter and LinkedIn.

Media Contact:
Denise Bradley
(267) 583-8267