Long-term Data Reinforce SPK-8011 Gene Therapy’s Potential for Hem A

21 patients experience 92% drop in average annual rate of bleeds

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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One-time treatment with the investigational gene therapy SPK-8011 led to sustained low bleed rates for people with hemophilia A in a Phase 1/2 clinical trial.

That’s according to data of up to 5 years of follow-up presented by the therapy’s developer, Spark Therapeutics, at the annual meeting of the American Society of Hematology (ASH), which was held in New Orleans last December. The oral presentation was titled “Long-Term Durable FVIII Expression with Improvements in Bleeding Rates Following AAV-Mediated FVIII Gene Transfer for Hemophilia A: Multiyear Follow-up on the Phase I/II Trial of SPK-8011.”

“For many individuals living with hemophilia A, current factor replacement therapies present limitations including the need for regular injections or infusions and unpredictable breakthrough bleeds,” Stacey Croteau, MD, study investigator and medical director at Boston Hemophilia Center, said in a press release.

“We are encouraged by these data and the potential for investigational SPK-8011 to further improve on current standards of care by providing a one-time, durable treatment option, and we will continue with participant follow-ups,” Croteau said.

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SPK-8011 uses viral vector to deliver healthy copy of F8 gene

Hemophilia A is caused by mutations in the F8 gene that provides instructions for making the clotting protein factor VIII (FVIII). SPK-8011 is designed to use a viral vector to deliver a healthy copy of this gene to cells in the liver, to trigger the production of functional FVIII.

Spark is funding a Phase 1/2 trial (NCT03003533) to test SPK-8011 in approximately 50 men with hemophilia A. All participants in the open-label study will be given a single dose of the gene therapy. Participants who complete the initial one-year study can choose to enter a long-term extension study (NCT03432520).

The ASH presentation covered data collected up to early October, at which point 23 participants had been treated with SPK-8011. The median follow-up time was over three years; two of the patients have been followed for at least five years.

Data showed that 21 of the 23 patients had an increase in FVIII activity that was sustained as of the latest follow-up, with “no apparent decrease in FVIII activity over time,” the researchers reported. The two patients who were the exceptions had experienced an immune reaction against the viral vector used in the gene therapy, as reported previously.

“The updated results of this Phase 1/2 study add to the growing body of preliminary evidence suggesting that investigational SPK-8011 provides durable FVIII expression for the treatment of hemophilia A,” said Gallia Levy, MD, PhD, chief medical and product strategy officer at Spark Therapeutics.

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No new safety issues identified

Among the 21 patients with sustained FVIII activity, there was a 92% decrease in the average annual rate of bleeds, which dropped from 11.62 bleeds per year before treatment to 0.98 bleeds per year after gene therapy. Most (76%) of the patients had less than one bleed requiring treatment per year, on average, and 90% had less than one yearly spontaneous bleed requiring treatment.

Decreases in bleeding rates were seen regardless of treatment patterns prior to gene therapy. Moreover, after gene therapy, there was a substantial decrease in the use of standard replacement therapies.

An updated safety analysis did not reveal any noteworthy new findings. So far, the only serious side effect related to the therapy was one case of increased liver enzymes, which had been reported previously.

“At Spark, we are focused on developing a gene therapy for people with hemophilia A that demonstrates safety, predictability, efficacy, and durability at the lowest effective dose with an optimal immunomodulatory regimen,” Levy said. “This latest readout reinforces the potential for investigational SPK-8011 to deliver on our commitment, and we look forward to its continued evaluation.”