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Gene therapy is an experimental treatment technique that uses genetic material to treat or prevent diseases. Gene therapy promises to achieve safe, effective, and durable expression of clotting factors and has become the standard therapy for hemophilia. At present, many companies around the world have entered the clinical trial stage for gene therapy for hemophilia.

What is hemophilia?

Hemophilia is a rare inherited bleeding disorder that impairs the body's ability to produce blood clots, leading to excessive bleeding and bruising. It is caused by mutations in the genes that encode for clotting factors, primarily factor VIII (FVIII: hemophilia A) and factor IX (FIX: hemophilia B). Hemophilia is typically treated with regular infusions of clotting factor concentrate, but this approach can be expensive, time-consuming, and poses a risk of developing inhibitors. Gene therapy offers a promising alternative by providing a long-lasting solution to hemophilia.

Overview of Gene Therapy for Hemophilia

Gene therapy for hemophilia involves the use of a modified virus as a delivery vehicle to introduce a functional copy of the clotting factor gene into the patient's cells. The goal is for the patient's cells to begin producing the missing clotting factors, reducing or eliminating the need for regular infusions of clotting factor concentrates.

There are two main types of gene therapy for hemophilia: ex vivo gene therapy and in vivo gene therapy. Ex vivo gene therapy involves extracting the patient's own cells, modifying them in the laboratory to produce the missing clotting factors, and then reinfusing them back into the patient. And in vivo gene therapy involves directly delivering the viral vector containing the functional clotting factor gene into the patient's body.

In recent years, significant advances have been made in the development of gene therapy for hemophilia. The most promising approach involves the use of adeno-associated viral vectors (AAV) to deliver the functional clotting factor gene. AAV vectors are capable of infecting non-dividing cells (e.g., hepatocytes, myocytes, etc.), maintaining the vector genome as a free polysome (with less risk of insertional mutagenesis), while being less immunogenic and having multiple capsid serotypes for transducing genes to specific target tissues. Therefore, AAV is currently the safest and most suitable viral vector for hemophilia gene therapy.

Fig. 1 Gene therapy strategies for hemophilia.Fig. 1 Gene therapy strategies for hemophilia. (Pickar A K, et al., 2018)

Current Gene Therapy Clinical Trials in Hemophilia

Several clinical trials are currently underway to assess gene therapy safety and efficacy for hemophilia. The results of these trials have been promising, with some patients achieving sustained levels of clotting factor activity that have eliminated the need for regular infusions of clotting factor concentrate.

One of the most promising gene therapy products is Valoctocogene Roxaparvovec (BMN 270), developed by BioMarin. BMN 270 is an AAV5-mediated gene therapy indicated for the treatment of Hemophilia A. Its advantage is that patients may only need to receive one treatment, and the liver cells can continue to express FVIII. The latest four-year research data show that this gene therapy can reduce the need for patients to use blood clotting factor VIII by 96%, and reduce bleeding events by more than 90%. BMN 270 has been awarded the Breakthrough Therapy Designation by the US FDA, the Priority Medicines (PRIME) Drug Designation by the European Union, and the Orphan Drug Designation by the EMA and FDA.

Similarly, Spark Therapeutics has developed SPK-8011, an AAV-based gene therapy for hemophilia A. In a phase 1/2 clinical trial, patients who received a single infusion of SPK-8011 achieved sustained levels of FVIII activity that significantly reduced bleeding episode frequency.

In addition, there are also some ongoing gene therapy candidates for hemophilia A and hemophilia B, including AMT-060 and AMT-061, being developed by UniQure, FLT180a by Freeline, SB-FIX by Sangamo Therapeutics, Fidanacogene elaparvovec (SPK-9001) by Spark Therapeutics and Pfizer, and SPK-8016 by Spark Therapeutics. These therapies use different approaches, such as genome editing or delivering a variant of the clotting factor gene, and are being tested in various clinical trials.

In conclusion, gene therapy offers a promising alternative to hemophilia care. Advances in gene therapy for hemophilia with viral vectors, animal models, target cell selection, and clinical therapeutic trials have advanced the development of new therapies. Currently, several clinical trials have demonstrated promising results, bringing hope for improving treatment options for hemophilia patients.


  • Pickar, A. K.; Gersbach, C. A. Gene therapies for hemophilia hit the mark in clinical trials. Nature Medicine, 2018, 24(2): 121-122.

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