Gene therapy is an experimental treatment technique that uses genes or genetic material to treat or prevent disease. Human clinical trials are underway to test potential gene therapies for hemophilia.

What is hemophilia?

Hemophilia is a genetic blood clotting disorder where patients do not make enough of the factors that allow blood to clot. Without these factors, patients cannot stop bleeding when they are injured. Patients with more severe forms of the disease can experience spontaneous bleeding around the joints.

What is gene therapy?

Gene therapy for hemophilia involves using a modified virus (which does not cause disease) to introduce a copy of the gene that encodes for the clotting factor that’s missing in patients. Following treatment with the virus, patients should begin producing their own clotting factor normally.

CRISPR/Cas9 is another strategy that could allow a patient’s body to produce their own blood clotting factor. It uses a piece of genetic material and an enzyme that acts like molecular scissors to repair the genetic fault that causes clotting factor deficiency.

Experimental gene therapies

AMT-060 is a gene therapy being developed by UniQure to treat hemophilia B. Early results from an ongoing two-cohort Phase 1/2, non-randomized, open-label, multi-center clinical trial (NCT02396342) — which included 10 patients with severe or moderately severe hemophilia B — demonstrated a clinically significant and sustained increase in factor IX activity, a substantial reduction in factor IX replacement therapy usage, and a complete cessation of spontaneous bleeding episodes.

AMT-061 is uniQure’s second gene therapy candidate for patients with hemophilia B. It is developed to deliver a variant of the F9 gene that encodes for clotting factor IX called FIX-Padua. This variant carries the instructions to make factor IX protein that is eight times more active than the normal protein. A harmless virus vector is used to direct the delivery of FIX-Padua to the patient’s body. Interim results of an ongoing Phase 2B study (NCT03489291) testing the safety and efficacy of AMT-061 in three patients with severe to moderately severe hemophilia B showed increased factor IX activity, reduced risk of bleeding, and no adverse events. A multicenter Phase 3 study (NCT03569891) evaluating the safety, efficacy, and tolerability of AMT-061 in hemophilia B patients is also underway.

FLT180a is a gene therapy being developed by Freeline. A Phase 1 clinical trial (NCT03369444) is currently recruiting patients with hemophilia B in the U.K. to test FLT180a. A second Phase 2/3 study (NCT03641703) is also recruiting participants in the same location to investigate the long-term safety and durability of factor IX activity in participants who have been treated with FLT180a gene therapy.

Sangamo Therapeutics is developing a genome editing therapy for hemophilia B called SB-FIX. A Phase 1/2 clinical trial (NCT02695160) is currently recruiting participants at several sites in the U.S. and the U.K.

Fidanacogene elaparvovec (SPK-9001) is a treatment for hemophilia B being developed in a partnership between Spark Therapeutics and Pfizer. This therapy is currently being investigated in a Phase 2 clinical trial (NCT02484092).

SPK-8011 is a gene therapy for hemophilia A being developed by Spark TherapeuticsPreliminary results from Phase 1/2 clinical trials (NCT03003533) indicated that all five participants in the first two dose cohorts have shown persistent, stable clotting factor levels in their blood.

Spark Therapeutics is developing another gene therapy called SPK-8016, which is designed to help hemophilia A patients who have developed inhibitors against their own clotting factors. Patients are currently being recruited for a Phase 1/2 clinical trial (NCT03734588) in the U.S. to determine the effective dosage of the treatment.

Valoctocogene roxaparvovec (BMN 270) is a gene therapy being developed by Biomarin to treat hemophilia A. The therapy is currently in Phase 1/2 clinical trials (NCT02576795).

SB-525 is a gene therapy being developed by Sangamo Therapeutics to treat hemophilia A. A Phase 1/2 clinical trial (NCT03061201) is currently recruiting about 20 adults with hemophilia A at sites across the U.S. to evaluate the safety, tolerability, and efficacy of the treatment.

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