SPK-8011 is an investigational gene therapy being developed by Spark Therapeutics for the treatment of hemophilia A, which is a bleeding disorder caused by mutations in the F8 gene. This gene encodes for factor VIII, a clotting factor in the blood.

How SPK-8011 works

SPK-8011 contains a modified virus that carries the human F8 gene under the control of a specific DNA sequence, which ensures its protein product, factor VIII, is only made in the liver.

When infused into a patient, the virus infects cells and delivers the bioengineered F8 gene into their nucleus. Recombinant human factor VIII protein is then synthesized in the liver only, which —if successful — will restore the normal blood clotting pathway.

The current standard of care for hemophilia A patients is repeated infusions of either plasma-derived or recombinant factor VIII into the bloodstream two to three times weekly, or in response to bleeding. If SPK-8011 is successful in clinical trials and approved by the U.S. Food and Drug Administration (FDA), a single infusion could be sufficient to restore normal levels of factor VIII in hemophilia A patients.

SPK-8011 in clinical trials 

In a Phase 1/2 open-label, non-randomized study (NCT03003533), 12 hemophilia A patients with endogenous (produced or synthesized within the organism) FVIII activity levels of less than 2 percent compared with normal levels were administered a single infusion of three doses of SPK-8011. Two patients received a low dose of SPK-8011, while three patients were given a medium dose, and seven received a high dose. The patients were then followed for 52 weeks to study changes from baseline in FVIII activity levels, and record any adverse events.

At 46 weeks, there was a 94% reduction in bleeds and a 95% reduction in needed FVIII infusions across all three doses. Stable factor VIII activity was observed in all participants in the low and medium doses. Five participants treated with the high dose of SPK-8011 also showed significant factor VIII activity, with a 100% reduction in bleeds, and a 99% reduction in needed FVIII infusions.

Factor VIII levels in two participants in the high-dose group decreased to less than 5%, probably because of an immune response in their bodies against the virus. One of these participants required hospitalization to receive infusions due to decreased factor VIII activity; this was scored as a serious adverse event.

No other adverse events were observed at 46 weeks, including factor VIII inhibitors in the blood, thrombotic events (abnormal blood clot formation), or abnormal liver function.

All 12 participants showed rapid clearance of the virus from body fluids. The median time to clear viral DNA from saliva, semen, and urine was two weeks.

Spark Therapeutics is enrolling hemophilia A patients by invitation in an observational multi-center clinical study (NCT03432520), in which about 100 patients who have received a single dose of SPK-8011 will be monitored for up to five years. This study, which aims to evaluate the long-term safety and efficacy of SPK-8011 in patients with hemophilia A, started in August 2018 and is scheduled to be completed by December 2022.

Additional information

SPK-8011 has been granted orphan drug designation and breakthrough therapy designation in the U.S. by the FDA, and orphan drug designation in Europe by the European Commission.

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