On January 10, 2021, biotechnology company BioMarin Pharmaceutical Inc. (“BioMarin”) shared positive data from its Phase 3 GENEr8-1 clinical trial. The clinical trial is evaluating an investigational gene therapy called valoctocogene roxaparvovec for adult patients with severe hemophilia A.

GENEr8-1 Trial

Altogether, 134 patients enrolled in the GENEr8-1 clinical trial. During the study, all participants received one dose of 6e13 vg/kg valoctocogene roxaparvovec. Next, follow-up data was collected over a 1+ year period, with a mean follow-up time of around 71.6 weeks. Researchers sought to understand whether this investigational AAV5 gene therapy was safer, more effective, and better tolerated than FVIII prophylactic therapy, the current standard-of-care for hemophilia A. AskBio describes how AAV gene therapy works:

The viral DNA is replaced with new DNA, and it becomes a precisely coded vector and is no longer considered a virus, as most of the viral components have been replaced. The AAV vector is then used to deliver normal copies of genes to the right tissues or organs in the body, but it now delivers the therapy that has been engineered into it.

During the GENEr8-1 trial, researchers found that:

• 107 patients were free of any bleeding episodes within 5 weeks of receiving valoctocogene roxaparvovec.
• One dose of this gene therapy reduced the annualized bleeding rate by 84%.
• Valoctocogene roxaparvovec was relatively safe and well-tolerated. However, about 16.5% of participants experienced some side effects. These included:
  • Infusion reactions
  • Headache
  • Nausea
  • Fatigue
  • Joint pain
  • Elevation of alanine aminotransferase and aspartate aminotransferase levels

This gene therapy received Breakthrough Therapy and Orphan Drug designations within the United States, as well as Orphan Drug designation in Europe. However, BioMarin is still working to achieve marketing approval.

Hemophilia A

Also known as Factor VIII deficiency, hemophilia A is an inherited genetic bleeding disorder caused by too little, or defective, Factor VIII, a clotting protein. Because of the autosomal recessive inheritance pattern, hemophilia A is usually only found in male patients. However, in rare cases, it may be found in females. An estimated 20,000 Americans have hemophilia A. Symptoms and symptom severity vary and may include:

• Easy bruising and bleeding
• Joint pain and swelling
• Digestive and urinary tract bleeding, leading to bloody stool or urine
• Excessive bleeding after surgery, dental work, cuts, vaccinations, or other similar activity
• Frequent and intense nose bleeds
• Irritability (in infants)
• Excessive menstruation or bleeding after childbirth
• Bleeding gums

Learn more about hemophilia A here.