SB-525 for Hemophilia A

SB-525 is an experimental gene therapy developed by Sangamo Therapeutics — in collaboration with Pfizer — to treat hemophilia type A.

Sangamo Therapeutics led Phase 1/2 clinical trials for the medication, but now has handed over its development to Pfizer, which will advance the gene therapy into Phase 3 clinical trials.

The U.S. Food and Drug Administration (FDA) granted SB-525 fast track and orphan drug designations, as well as regenerative medicine advanced therapy status.

What is hemophilia type A?

Hemophilia refers to a group of bleeding disorders, usually genetically inherited. People with these disorders do not produce enough blood clotting factors, which can cause uncontrolled bleeding. In the case of hemophilia type A, patients make too little or no clotting factor VIII.

The development of treatments that rely on gene therapy techniques may help people with hemophilia overcome problems associated with this disease by inducing the production of clotting factors by the patient’s own cells.

How does SB-525 work?

The goal of SB-525 treatment is to reduce or eliminate the need for replacement therapy by inducing cells to naturally produce their own clotting factor VIII. 

SB-525 is composed of a small portion of genetic material with the code necessary for the production of factor VIII. Once inside cells, it is hoped that this genetic material will bind to the patient’s own genetic material and allow the production of factor VIII by the cell’s protein-making machinery. 

The genetic information within SB-525 is carried and delivered to liver cells, where clotting factors are normally produced, using a harmless virus called AAV. A single SB-525 treatment may be sufficient to allow a durable production of clotting factor VIII in liver cells. Once made by liver cells,  the clotting factor will be carried to the bloodstream and should assist in the formation of blood clots, protecting against bleeding complications seen in hemophilia patients.

SB-525 in clinical trials

Results from a preclinical study showed long-term production of human clotting factor VIII in mouse models of hemophilia A when genetic information was delivered to the liver of the animals using AAV.

A Phase 1/2, open-label, adaptive, and dose-ranging study (NCT03061201) is currently evaluating the safety, tolerability, and efficacy of SB-525 in treating adults with severe hemophilia A. During the trial, patients received one of four increasing doses of the therapy.

The most recent results from the trial were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2019 Congress in Melbourne, Australia. They showed that all patients had increases in clotting factor VIII in their body. The patients who received the highest dose showed normal range levels of the clotting factor within five weeks of receiving the therapy. Most patients showed a reduction in spontaneous bleeds and needed less replacement therapy.

SB-525 also was well-tolerated, with only one serious adverse event being reported — a single participant experienced fever and low blood pressure six hours following the therapy. These complications were resolved with treatment, and the patient was discharged within 24 hours.

A Phase 3 clinical trial (NCT03587116) is evaluating the current effectiveness and safety of preventive replacement therapy in the usual care setting in hemophilia type A and type B patients. The results of this study will serve as the control group for subsequent Phase 3 gene therapy studies for both types of hemophilia. The primary outcome measure of the trial will be the bleeding rate. The incidence of adverse events will also be recorded. The trial is currently recruiting an estimated 125 patients at 65 locations worldwide, and is expected to conclude in 2021.

Other information

The most common adverse events associated with SB-525 treatment are liver enzyme elevation, fever, low blood pressure, fatigue, muscle pain, and tachycardia, which is an abnormally fast heart rate.


Last updated: Jan. 8, 2020


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