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FDA approves Roctavian gene therapy for severe Hemophilia A in adults.

Halfway through the year 2023, BioMarin bagged the approval for an “adeno-associated virus serotype 5 (AAV5)” gene therapy by the United States Food and Drug Administration (FDA). The therapy is for adults with a life-threatening and rare genetic condition known as Hemophilia A. In this article we will discuss about the novel therapy and the studies leading to its approval. 

Hemophilia A, also referred to as an X-linked disorder affects 1 in 5,000 male births. The sex-linked disorder is more prevalent in females than in the male cohort.1 Globally found in all ethnicities and races, 185,318 people were living with the bleeding disorder till the last survey of 2021.2 People with Hemophilia (PWH) can have a severe, moderate, or mild protein deficiency- FVIII. The mild group has a clotting ability of 6%-40% range while the severe group has only <1% clotting ability. It is limited but a severe bleeding disorder that occasionally occurs due to a genetic mutation in the X chromosome. It is branched into two types – A and B, with Hemophilia A being four times more predominant than subtype B. The alteration in the F8 gene on the X chromosome’s long arm results in the insufficient production of a coagulation/clotting factor termed FVIII.3 The deficiency in the glycoprotein FVIII leads to excessive bleeding in situations such as wounds/injuries, surgeries, and bruises as the sparse supply inhibits the achievement of hemostasis hence slowing wound healing.

Currently available treatments

Prophylaxis is the standard treatment regimen recommended by the World Health Organization (WHO) and the World Federation of Hemophilia (WFH). Prophylaxis is available as concentrates of the clotting factor derived from plasma (source is human) or as a recombinant factor (synthetically prepared).4 The treatment is administered regularly to maintain the clotting ability to inhibit progression into fatal outcomes. In addition to the factor-derived treatment, there are drug-based medications such as Hemlibra/ Emicizumab, Amicar, and Desmopressin.4 The setback faced with these current treatments is that they must be administered regularly and should be provided lifelong.  

Gene therapy is the new promising option towards the treatment of genetic disorders and has been reported to be successful. Roctavian is the only gene therapy recently approved as a single dose for adults living with severe hemophilia A. The major advantage of using gene therapy over prophylaxis is that the former is usually a single-dose infusion treatment hence more convenient.5

Roctavian, the viral vector gene therapy

Roctavian also termed “valoctocogene roxaparvovec-rvox” is a one-shot intravenous adeno-associated virus vector gene therapy that aims to deliver the gene responsible to produce the glycoprotein FVIII and in turn, shrink the demand for prophylaxis and excessive bleeding episodes. It is used for adults reported to have severe Hemophilia A (<1 IU/dL) and negative for adeno-associated virus serotype 5 (AAV5) antibodies.6

Adeno-associated viral (AAV) vectors are designed from non-pathogenic DNA viruses and target the liver cells. The vector carrying the gene of interest is delivered into the peripheral veins which further enters the cell of interest (hepatocytes). The machinery of transcription and translation begins as the gene of interest enters the nucleus. The overall process results in the production of the protein FVIII and in turn reduces the adverse bleeding scenarios.7

Efficacy, dosage, and safety of Roctavian

The FDA approved the gene therapy of Roctavian based on large phase 3 clinical trial named GENEr8-1 for Hemophilia A.7 The clinical trial was conducted in male cohorts with severe Hemophilia A between the age group of 18-70 years. 134 patients who were on prophylaxis earlier underwent the gene therapy treatment.8 Out of all, prospective data was available for 112 patients 3 years post-Roctavian treatment. Key study findings were as follows:

  • The patients presented a decline in the annual bleeding rate (ABR) from 5.4 bleeds/year to 2.6 bleeds/year.
  • A reduction in spontaneous bleeding episodes was also communicated in the same cohort post-therapy from 2.3 bleeds/year to 0.5 bleeds/year.

Overall, the patients post three-year monitoring were positively responding to the gene therapy without the need for additional prophylaxis supplements. The most common side effects reported were abdominal pain, headaches, sickness, lethargy, or allergic reactions.

About the Author: Pragya Agarwal is a postgraduate in Infection Biology from Germany. She is passionate about science and innovations and is keen in learning and presenting data to broader audience. Click on the link to get in touch with Pragya on LinkedIn. 


  1. Konkle BA, Nakaya Fletcher S. Hemophilia A. 2000 Sep 21 [Updated 2023 Jul 27]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from:
  2. National Hemophilia Foundation. Available at: Accessed on 5 August 2023.
  3. Sarmiento Doncel S, Díaz Mosquera GA, Cortes JM, et al. Haemophilia A: A Review of Clinical Manifestations, Treatment, Mutations, and the Development of Inhibitors. Hematology Reports. 2023 Feb 16;15(1):130–50.
  4. World Federation of Hemophilia Available at: Accessed on 5 August 2023.
  5. U.S. Food and Drug Administration Approves BioMarin’s ROCTAVIANTM (valoctocogene roxaparvovec-rvox), the First and Only Gene Therapy for Adults with Severe Hemophilia A. Available at: Accessed on 5 August 2023.
  6. Blair HA. Valoctocogene Roxaparvovec: First Approval. Drugs. 2022 Sep;82(14):1505–10.
  7. Castaman G, Di Minno G, De Cristofaro R, et al. The Arrival of Gene Therapy for Patients with Hemophilia A. IJMS. 2022 Sep 6;23(18):10228.
  8. BioMarin - Roctavian Approval Press Release. Accessed on 5 August 2023.
  9. Summary of product characteristics. anx_156641_en.pdf. Available at: Accessed on 5 August 2023

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