SPK-8016 is an investigational gene therapy being developed by Spark Therapeutics to treat hemophilia A patients with inhibitors.

How SPK-8016 works

Hemophilia A is characterized by little or no factor VIII in the blood. This is a protein that plays a crucial role in the blood clotting cascade. SPK-8016 aims to boost factor VIII levels in the blood of hemophilia A patients who develop inhibitors, or antibodies, that cause factor VIII replacement therapies to fail.

Nearly 30 percent of hemophilia A patients who receive plasma-derived or recombinant factor VIII infusions develop inhibitors, which are antibodies that mark the infused factor VIII for destruction by the immune system. The result is the failure of therapies that aim to boost factor VIII levels, and the risk of life-threatening prolonged bleeding and other complications.

SPK-8016 is a modified adeno-associated virus (AAV) that carries a bioengineered gene whose protein product can suppress factor VIII inhibitors.

When infused into the bloodstream of hemophilia A patients, this benign AAV delivers the bioengineered anti-factor VIII inhibitor-encoding gene into the nucleus of cells in tissues and organs, such as the liver, retina, cardiac and skeletal muscles, and others. Depending on the type of promoter, the recombinant protein will be made in a particular tissue. For example, if the recombinant gene is under the control of a liver-specific promoter, the recombinant protein will be produced only in the liver. (Promoters are regions in the DNA where transcription factors or proteins controlling the activity of specific genes bind to). The recombinant gene product is expected to neutralize the inhibitors against factor VIII and boost factor VIII levels or activity in the patient’s body, with the intent of restoring the normal blood-clotting pathway.

SPK-8016 in clinical trials

Spark Therapeutics is enrolling up to 30 adults with severe hemophilia A (both with and without inhibitors against factor VIII in the blood) for a Phase 1/2, multi-center, open-label, and non-randomized two-part clinical trial (NCT03734588).

Part one will evaluate the safety, effectiveness, and tolerability of SPK-8016 in patients who do not have any measurable inhibitor against factor VIII in their blood. Data from part 1 will help in determining the optimal dose and study design for the trial’s part 2. In this part, SPK-8016 will be tested in patients with factor VIII inhibitors in their blood.

Following treatment, patients will be followed for up for 52 weeks and evaluated for:

  • treatment-related side effects;
  • liver function;
  • number of spontaneous and traumatic bleeding events;
  • number of factor VIII infusions needed;
  • peak and steady-state factor VIII activity levels;
  • clearance of SPK-8016 from bodily fluids such as saliva, blood, semen, and urine, and;
  • incidence of an immune response against the treatment.

This study is being conducted at the Mississippi Center for Advanced Medicine, Children’s Hospital of Philadelphia, and Virginia Commonwealth University School of Medicine in the U.S.; more information is available here.  Final data is expected to be collected in April 2020.

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