Hemophilia gene therapy approved for marketing

January 04, 2023

Hemophilia is an X-linked recessive genetic bleeding disorder, predominantly made up of hemophilia A and hemophilia B. The former is deficient in coagulation factor VIII (FVIII), and the latter is deficient in coagulation factor IX (FIX), both of which are caused by mutations in the corresponding coagulation factor gene and manifest as spontaneous bleeding or excessive bleeding after minor injury [1]. Hemophilia A is the most common hemophilia clinically, accounting for about 80%-85% of hemophiliacs while hemophilia B accounting for about 15% of hemophiliacs[2]. Other forms of hemophilia include hemophilia C, lack of coagulation factor XI, and acquired hemophilia (that is, acquired coagulation factor deficiency, which is an autoimmune disease). According to public data, about 400,000 people worldwide suffer from hemophilia.

The treatment methods for hemophilia mainly include alternative therapy and gene therapy. The year of 2022 has been full of good news for gene therapy for hemophilia.

Gene Therapy for Hemophilia A Receives EC Approval

In August 2022, BioMarin announced that the European Commission (EC) approved the conditional marketing of its gene therapy RoctavianTM (Valoctocogene Roxaparvovec) for the treatment of hemophilia A, which is used to treat adult patients with severe hemophilia A. Patients are required to have no history of factor VIII inhibitors and no detectable antibodies to adeno-associated virus serotype 5 (AAV5). It is worth mentioning that RoctavianTM is the world's first approved gene therapy for the treatment of hemophilia A. The therapy has greatly reduced the average frequency of bleeding events and the average annual coagulation factor VIII infusion times of patients with this severe bleeding disease.


Fig 1: Phase III clinical trial data of BioMarin’s Valoctocogene Roxaparvovec

Image credit: New England Journal of Medicine

Gene therapy for hemophilia B launched in US

Recently, the U.S. FDA approved CSL Behring's gene therapy Hemgenix®️ (etranacogene dezaparvovec) to be launched in the United States. This therapy is indicated for the treatment of adult patients with hemophilia B who are currently taking factor IX prophylaxis,  have current or past life-threatening bleeding, or have recurrent severe spontaneous bleeding. Hemgenix®️ is the first gene therapy approved for the treatment of hemophilia B in the world, and the first gene therapy approved for the treatment of hemophilia in the United States. As data (presented on uniQure official website; adapted in Figure 2) demonstrate that the therapy effectively reduced the occurrence of bleeding events in patients with good safety.


Fig 2: Phase III clinical trial data of CSL Behring’s etranacogene dezaparvovec

Image source: uniQure official website

The approval of a gene therapy or any effective therapy for hemophilia is of great significance to patients with hemophilia. Additional research is still needed to claim the victory over hemophilia.

GemPharmatech’s Mouse Models for Preclinical Research in Hemophilia

Mouse models play a vital role in preclinical research and translational research, and an appropriate disease model in mice simulate the pathogenesis and key symptoms of human patients. GemPharmatech has developed the B6-F8-KO (strain number: T004727) mouse model. The strategy knocked out several coding exons of the F8 gene in C57BL/6JGpt mice, and caused the loss of FVIII protein through a frameshift mutation. This model can be used in the screening of drugs for the treatment of hemophilia A, and in the evaluation of the effect and safety of gene therapy.

Phenotype validation of B6-F8-KO mice:


Fig 3. Detection of blood loss and coagulation time in B6-F8-KO mice

After the tail vein was snipped, the bleeding volume and coagulation time of B6-F8-KO mice were significantly increased compared with the control mice.

Other hemophilia-related models

Strain number

Strain name

Technology type











1. Mehta, P., & Reddivari, A. (2021). Hemophilia. In StatPearls. StatPearls Publishing.

2. Fischer K. Low-dose prophylaxis for severe haemophilia: a little goes a long way[J]. Haemophilia, 2016, 22(3): 331-333.

3. Biomarinpress release

4. FDA press release