The US Food and Drug Administration (FDA) approved Roctavian, an adeno-associated virus vector-based gene therapy for the treatment of adults with severe hemophilia A without pre-existing antibodies against serotype 5 of the virus adeno-associated 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 problems due to the increased risk of uncontrolled bleeding,” said Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.
He added that the approval, dated June 29, “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.”
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 allows blood to clot. The disorder mainly affects men. This deficiency in FVIII causes those affected to bleed uncontrollably and bleed longer than people who do not have the condition. The frequency and severity of bleeding episodes depends on the amount of FVIII protein a person produces. Severe hemophilia A is characterized by especially low levels of FVIII (less than 1% in the blood) and accounts for about 60% of all cases. This condition is capable of causing bleeding in vital organs of the body, such as the kidneys and brain, which can be life-threatening if left untreated.
Roctavian is a one-time gene therapy product administered as a single dose via intravenous infusion. It consists of a viral vector that carries a gene for coagulation factor VIII. The gene is expressed in the liver to increase blood levels of FVIII and reduce the risk of uncontrollable bleeding.
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 factor VIII replacement therapy. Efficacy was established based on results from a cohort of 112 patients followed for at least 3 years after treatment with Roctavian. After infusion, the mean annualized bleeding rate decreased from 5.4 bleeds per year at baseline to 2.6 bleeds per year. Most patients assigned mRoctavian received corticosteroids to suppress the immune system to make the gene therapy effective and safe. The response to treatment with Roctavian may decrease over time.
The most common adverse reactions associated with this medication included mild changes in liver function, headache, nausea, vomiting, fatigue, abdominal pain, and infusion-related reactions. Close monitoring for side effects and elevation of liver enzymes is recommended with Roctavian administration. In some cases, treatment was observed to increase FVIII activity levels above normal limits. An increase in FVIII activity can raise the risk of thromboembolic events (blood clots that can cause damage by blocking blood flow). The introduction of the Roctavian product DNA sequence may carry a theoretical risk of developing hepatocellular carcinoma (liver cancer) or other types of cancer. No cases of thromboembolic events or cancers associated with Roctavian were observed in clinical studies.
This application received Orphan, Breakthrough Therapy, Advanced Regenerative Medicine Therapy, and Priority Review designations. The FDA granted approval of Roctavian to BioMarin Pharmaceutical Inc.
Roctavian is approved with AAV5 DetectCDx, a companion diagnostic test intended to help healthcare providers identify patients who may benefit from receiving Roctavian to treat hemophilia A. The test was shown to be effective in detecting anti- preexisting AAV5, which may make gene therapy less effective or ineffective. Clinical study data from patients with hemophilia A who received Roctavian after being identified as eligible for AAV5 DetectCDx (patients without pre-existing anti-AAV5 antibodies), supported the safety and efficacy of AAV5 DetectCDx for its intended use as a companion diagnostic to Roctavian. The FDA granted approval of AAV5 DetectCDx to ARUP Laboratories.
