SPK-8016 is an investigational gene therapy that Spark Therapeutics is developing for hemophilia A patients with inhibitors.

It is designed to restore the normal blood-clotting pathway in people with the genetic disorder for whom replacement therapies do not work.

How does the gene therapy candidate work?

People with hemophilia A have little or no factor VIII in their blood. This is a protein that plays a crucial role in the blood clotting cascade that stops bleeding when an injury occurs. 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.

As many as 30% of hemophilia A patients who receive plasma-derived or recombinant factor VIII infusions develop inhibitors. 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 gene therapy that uses a modified adeno-associated virus (AAV) to deliver a piece of genetic code to cells in the body in order to restore the production of a form of factor VIII. Researchers expect that the recombinant gene product will boost factor VIII levels and activity in the patient’s body, thereby restoring the normal blood-clotting pathway.

SPK-8016 in clinical trials

Researchers are investigating SPK-8016 in a Phase 1/2, multi-center, open-label, and non-randomized two-part clinical trial (NCT03734588).

The study enrolled 30 adults with severe hemophilia A, both with and without inhibitors against factor VIII in the blood. To be included in the trial, patients had to have factor VIII activity lower than 1%, or between 1% and 2% but with either more than 10 bleeding events in the past year or be taking preventive measures (prophylaxis) to avoid bleeding.

Part one of the study is evaluating the safety, effectiveness, and tolerability of SPK-8016 in patients who did not have any measurable inhibitor against factor VIII in their blood.

The preliminary results from four patients were presented at the European Association for Haemophilia and Allied Disorders 2021 Virtual Congress, recently held online.

The four patients received a single intravenous (IV or into-the-vein) dose of  5×1011 vector genomes per kilogram (vg/kg) of SPK-8016. The results showed that by the data cutoff of October 2020, the treatment had increased the production of factor VIII from 5.9% to 21.8%.

At patient follow-up meetings, 15 to 18 months after the infusion, the annualized infusion rate had dropped 98%. The annualized infusion rate is the number of factor VIII infusions patients need per year. The annualized bleed rate, or the number of bleeding events per year, had dropped by 85%. None of the patients had developed factor VIII inhibitors by the time of their follow-ups.

Researchers will use data from part 1 of the trial to determine the optimal dose for part 2. In this second part, they will test SPK-8016 in patients with factor VIII inhibitors in their blood.

Following treatment, the participants in each part of the trial will be followed for up to 52 weeks (one year). All of them will be evaluated for treatment-related side effects, liver function, and the number of spontaneous and traumatic bleeding events. The team also will record the number of factor VIII infusions needed, peak and steady-state factor VIII activity levels, clearance of SPK-8016 from the body, and the incidence of an immune response against the treatment.

This study is running at multiple locations in the U.S. Final results will be available in December 2022.


Last updated: Feb. 16, 2021


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