A mutation in the gene that makes factor VIII (FVIII), a protein that facilitates blood clots, causes Haemophilia A, a rare genetic bleeding illness. Males are primarily affected by the illness. Affected individuals bleed uncontrollably and for a more extended period than those without the illness due to this FVIII deficiency. The amount of FVIII protein an individual produces determines the severity and frequency of bleeding episodes. About 60% of all instances of severe hemophilia A are characterized by extremely tiny amounts of FVIII (less than 1% in the blood).Â
If severe Haemophilia A is not treated, it may lead to bleeding into the brain and kidneys, which can be fatal. FVIII alternative therapy or an antibody-based drug is frequently used to treat severe Haemophilia A to increase blood clotting and decrease bleeding risk. To treat adults with severe Haemophilia A who do not already have antibodies to adeno-associated virus serotype five discovered by an FDA-approved test, the U.S. Food and Drug Administration has approved Roctavian, an adeno-associated viral vector-based gene therapy.Â
The bleeding disorder hereditary Haemophilia A has the potential to be quite dangerous. The increased risk of uncontrolled bleeding in severe Haemophilia A cases can result in potentially fatal health problems, according to Peter Marks, M.D., Ph.D., head of the FDA’s Centre for Biologics Evaluation and Research. “Today’s approval represents a significant step forward in the availability of treatment options for people with this bleeding disorder, and gene therapy may help patients avoid the need for ongoing routine therapy,”Â
A single intravenous infusion is used to provide the gene therapy drug Roctavian. A viral vector in Roctavian carries the clotting factor VIII gene. The gene is expressed in the liver to raise blood levels of FVIII and lower the danger of uncontrolled bleeding.Â
In a multi-nation research, adult men between 18 and 70 with severe hemophilia A who had previously received Factor VIII replacement therapy had their safety and efficacy with Roctavian assessed. Findings from a cohort study group of 112 patients monitored for at least three years following Roctavian medication were used to determine effectiveness.
The mean annualized bleeding rate dropped from 5.4 bleeds annually at baseline to 2.6 bleeds per year following the infusion. For gene therapy to be efficient and secure, most patients who received Roctavian also received corticosteroids to suppress the immune system. The effectiveness of Roctavian treatment may deteriorate over time.Â
Mild abnormalities in liver function, headaches, nausea, vomiting, exhaustion, stomach pain, and infusion-related responses were the most frequently reported side effects of Roctavian. With the administration of Roctavian, close observation is indicated for infusion-related events and elevated liver enzyme levels. In some instances, treatment with Roctavian was seen to raise FVIII activity levels above the normal range.
The risk of thromboembolic incidents (blood clots that can injure by obstructing blood flow) may increase as FVIII activity rises. The introduction of the DNA sequence of the Roctavian product may theoretically increase the risk of hepatocellular carcinoma (liver cancer) or other cancers. Clinical investigations found no evidence of malignancies or thromboembolic events linked to Roctavian.Â
The AAV5 DetectCDx, a companion diagnostic test designed to assist medical professionals in locating patients who might benefit from receiving Roctavian to treat hemophilia A, is approved in combination with Roctavian. The test detected anti-AAV5 antibodies that may render gene therapy inefficient or less effective.
The AAV5 DetectCDx was found to be safe and effective for use as a companion diagnostic to Roctavian in clinical study data from hemophilia A patients who received Roctavian after being determined to be eligible by the AAV5 DetectCDx (patients without pre-existing anti-AAV5 antibodies). The FDA approved the AAV5 DetectCDx for use by ARUP Laboratories.Â
