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Blood sample for hemophilia test, an inherited genetic disorder
Hemophilia A is a rare genetic bleeding disorder that occurs mostly in males due to a mutation in the gene that produces factor VIII, a protein that enables blood to clot.

FDA Approves First Gene Therapy for Adults with Severe Hemophilia A

Roctavian recipients should be closely monitored for infusion-related reactions and liver enzyme elevation

U.S. Food and Drug Administration
Published:Jul 03, 2023
|3 min read
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The U.S. Food and Drug Administration recently approved Roctavian, an adeno-associated virus vector-based gene therapy for the treatment of adults with severe hemophilia A without preexisting antibodies to adeno-associated virus serotype five (AAV5) detected by an FDA-approved test.

“Hereditary hemophilia A is a potentially serious bleeding disorder. Severe cases of hemophilia A can cause life-threatening health issues due to increased risk of uncontrolled bleeding,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval represents an important advance in providing treatment options for patients with this bleeding disorder, and treatment with gene therapy may reduce the need for ongoing routine therapy.”

What is hemophilia A?

Hemophilia A is a rare genetic bleeding disorder that occurs due to a mutation in the gene that produces factor VIII (FVIII), a protein that enables blood to clot. The disorder primarily affects males. This deficiency in FVIII causes affected individuals to have uncontrolled bleeding and bleed longer than people who do not have the condition. 

The frequency and severity of bleeding episodes depend on how much FVIII protein a person produces. Severe hemophilia A is characterized by particularly low levels of FVIII (less than 1 percent in the blood) and represents about 60 percent of all cases. Severe hemophilia A may result in bleeding into vital body organs such as the kidneys and brain, which can be life-threatening if left untreated. 

Treatment for severe hemophilia A usually involves the use of FVIII replacement therapy or an antibody-based medication to improve the ability of blood to clot and reduce the likelihood of bleeding.

Roctavian is a one-time gene therapy product administered as a single dose by intravenous infusion. Roctavian consists of a viral vector carrying a gene for FVIII. The gene is expressed in the liver to increase blood levels of FVIII and reduce the risk of uncontrolled bleeding. 

Safety and side effects of Roctavian

The safety and effectiveness of Roctavian were evaluated in a multinational study in adult men, 18 to 70 years of age, with severe hemophilia A who were previously treated with FVIII replacement therapy. Effectiveness was established based on results from a cohort of 112 patients followed up for at least three years after Roctavian treatment. 

Following the infusion, the mean annualized bleeding rate decreased from 5.4 bleeds per year at baseline to 2.6 bleeds per year. The majority of patients who received Roctavian received corticosteroids to suppress the immune system for the gene therapy to be effective and safe. Treatment response to Roctavian may decrease over time. 

The most common adverse reactions associated with Roctavian included 

  • mild changes in liver function, 

  • headache, 

  • nausea, 

  • vomiting, 

  • fatigue, 

  • abdominal pain, and 

  • infusion-related reactions. 

Close monitoring for infusion-related reactions and liver enzyme elevation is advised with Roctavian administration. In some cases, treatment with Roctavian was observed to increase FVIII activity levels above the normal limits. An increase in FVIII activity may increase the risk of thromboembolic events (blood clots that can cause harm by impeding blood flow).

Introduction of the Roctavian product’s DNA sequence may carry the theoretical risk of developing hepatocellular carcinoma or other cancers. No instances of thromboembolic events or cancers associated with Roctavian were observed in clinical studies. 

This application received Orphan, Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Priority Review designations. And the FDA granted approval of Roctavian to BioMarin Pharmaceutical Inc.

Roctavian is approved with the AAV5 DetectCDx™, a companion diagnostic test intended to help health care providers identify patients who may benefit from receiving Roctavian to treat hemophilia A. The test was proven effective in detecting preexisting anti-AAV5 antibodies, which may render the gene therapy less effective or ineffective. 

Clinical study data from hemophilia A patients who received Roctavian after being identified as eligible by the AAV5 DetectCDx™ (patients without preexisting anti-AAV5 antibodies), supported the safety and effectiveness of the AAV5 DetectCDx™ for its intended use as a companion diagnostic to Roctavian. The FDA granted approval for the AAV5 DetectCDx™ to ARUP Laboratories.

- This press release was originally published on the U.S. Food and Drug Administration website