Spark Therapeutics Announces Long-Term Efficacy and Safety Data for SPK-8011 Gene Therapy in Hemophilia A

Today, Spark Therapeutics, a subsidiary of Roche, presented the latest data from its Phase 1/2 clinical trial of the investigational gene therapy SPK-8011 for the treatment of hemophilia A at the 2020 International Society on Thrombosis and Haemostasis (ISTH) Virtual Congress. The latest data showed that among 12 patients treated with three different doses of the gene therapy, the annualized bleeding rate (ABR) was reduced by 91% and factor VIII infusion consumption was reduced by 96% after 2 to 3.3 years of follow-up, with stable and durable factor VIII expression observed in patients. The Phase 3 clinical trial of this investigational therapy is expected to commence in 2021.

Hemophilia is a rare inherited bleeding disorder in which blood takes an unusually long time to clot due to a deficiency in one of several clotting factors. The incidence of hemophilia A is approximately four times that of hemophilia B. Hemophilia A is characterized by mutations in the gene encoding coagulation factor VIII, leading to impaired coagulation and an increased risk of bleeding. The current standard of care for hemophilia A involves repeated intravenous infusions of plasma-derived or recombinant coagulation factor VIII to control and prevent bleeding. There is a significant unmet need for innovative therapies among patients with hemophilia.

SPK-8011 is a novel adeno-associated virus (AAV) vector utilizing the AAV-LK03 capsid, carrying a codon-optimized human coagulation factor VIII transgene under the control of a liver-specific promoter. The U.S. Food and Drug Administration (FDA) has granted orphan drug designation and breakthrough therapy designation to this investigational therapy.

In this Phase 1/2 clinical trial, a total of 14 patients received treatment with SPK-8011, including two patients who received a low dose (5E11 vg/kg), three who received a medium dose (1E12 vg/kg), and nine who received a high dose (2E12 vg/kg) of the gene therapy. Two patients treated with the high-dose gene therapy exhibited absent factor VIII expression, likely due to an immune response to the adeno-associated virus (AAV) capsid. The remaining 12 patients demonstrated stable and sustained factor VIII expression.

All 14 subjects demonstrated rapid clearance of the AAV vector from semen, serum, saliva, and urine within two weeks following administration. Six weeks post-dosing, the AAV vector was undetectable in peripheral blood mononuclear cells (PBMCs), semen, serum, saliva, and urine in all subjects.

Dr. Federico Mingozzi, Chief Scientific Officer at Spark Therapeutics, stated, “We are highly encouraged by these interim data, which continue to demonstrate an acceptable safety profile and a substantial reduction in bleeding episodes among patients over a mean observation period of more than two years. Our R&D focus is on optimizing the dosing and immunomodulatory regimens prior to initiating Phase 3 clinical studies, with the aim of demonstrating the safety, predictability, efficacy, and durability of gene therapy for hemophilia A at the minimum effective dose and with the optimal immunomodulatory regimen.”

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