Rare Daily Staff

Spark Therapeutics said updated data from its ongoing phase 1/2 clinical trial of its experimental gene therapy SPK-8011 in hemophilia A produced sustained factor VIII expression in 16 of 18 patients with up to fours years of follow-up as of May 3, 2021.

Principal Investigator Lindsey George, of the Perelman School of Medicine, University of Pennsylvania and Children’s Hospital of Philadelphia, was scheduled to report the data during the International Society of Thrombosis and Hemostasis 2021 Virtual Congress.

“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, chief medical officer of 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.”

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 United States 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.

SPK-8011 is a novel bio-engineered adeno-associated viral vector utilizing the AAV-LK03 capsid, also referred to as Spark200, and contains a codon-optimized human factor VIII gene under the control of a liver-specific promoter. The Food and Drug Administration granted orphan disease designation and breakthrough therapy designation in the United States. The European Commission also granted orphan designation to SPK-8011.

Eighteen participants in the Phase 1/2 trial received a single administration of investigational SPK-8011 in four dose cohorts. In the 16 patients with sustained FVIII expression, there was a 91.2 percent reduction in annualized bleed rate and a 97 percent reduction in annualized FVIII infusion rate 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 four years of follow-up. As previously reported, two of the 17 participants with more than 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 elevations. All 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 (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 adverse event. The event was subsequently resolved.

Photo: Gallia Levy, chief medical officer of Spark Therapeutics

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