ARUP Laboratories Makes History with Diagnostic Test for Hemophilia A
Hemophilia A is an inherited bleeding disorder that mostly affects males. About 400 babies are born with this rare disease every year in the U.S. The condition can lead to spontaneous bleeding into muscles, organs, and joints as well as prolonged bleeding following injuries or surgery.
In June, the U.S. Food and Drug Administration (FDA) approved ROCTAVIANTM, a new gene therapy treatment for patients with severe hemophilia A. Simultaneously, the FDA approved the first-ever diagnostic test designed to identify patients who are eligible for gene therapy. That test, known as AAV5 DetectCDxTM, was developed by ARUP Laboratories, a nonprofit enterprise of the University of Utah.
Benefits of Gene Therapy for Severe Hemophilia A
Hemophilia A is caused by a mutation of the gene that encodes Factor VIII, a clotting protein. Patients with severe hemophilia A typically have less than 1% active Factor VIII in their bloodstream. Without the ability to clot and maintain normal hemostasis, patients may experience serious bleeding complications. Patients are infused with clotting factor several times weekly to reduce this risk.
ROCTAVIANTM is a one-time infusion therapy that can help patients with severe hemophilia A make their own Factor VIII. It uses a modified adeno-associated virus, AAV5, to deliver a functional Factor VIII gene to the liver cells into the bloodstream. Adeno-associated viruses are not known to cause disease in humans, and they can be modified in the laboratory to act as vectors to deliver a gene into cells.
ROCTAVIANTM can reduce annual bleed rates in patients. It has been proven to be an effective and safe therapy for severe hemophilia A patients who don’t have pre-existing anti-AAV5 antibodies. It is not approved for use in patients with pre-existing anti-AAV5 antibodies. That is why ARUP’s AAV5 DetectCDxTM companion diagnostic test is so important.
Significance of AAV5 DetectCDx Test
First, a hematologist determines they have a patient who is a good candidate for ROCTAVIANTM gene therapy. Next, the patient is tested for pre-existing anti-AAV5 antibodies using the AAV5 DetectCDxTM test. The results show if the patient is eligible for ROCTAVIANTM therapy.
AAV5 DetectCDxTM determines whether anti-AAV5 antibodies are present in the blood’s plasma. For patients, it’s a simple blood draw. In the lab, technicians separate the plasma from the blood, then freeze it and ship it to ARUP Laboratories for analysis.
The FDA granted ARUP Laboratories approval for AAV5 DetectCDxTM processing at a single site. We are the only laboratory in the U.S. performing this assay in this clinical setting. When someone with severe hemophilia A chooses to embark on ROCTAVIANTM gene therapy, AAV5 DetectCDxTM test results give patients and physicians confidence that preexisting AAV5 antibodies are not present.
Helping Patients Receive ROCTAVIAN
To create the AAV5 DetectCDxTM diagnostic test, ARUP Laboratories collaborated with BioMarin Pharmaceutical Inc., the developer of ROCTAVIANTM gene therapy. Our work has helped advance the field of precision medicine, which determines which patients will be best served by specific therapies.
ARUP Laboratories was well-positioned to collaborate with BioMarin to develop the AAV5 DetectCDxTM test. We have the breadth of medical and laboratory medicine expertise needed to deliver on a high complexity project like this. In our PharmaDX group, we have a quality management system that meets FDA requirements for development and commercialization of companion diagnostic assays. That’s one reason why BioMarin approached us for the collaboration. We also have the expertise needed to take such a test through both U.S. and ex-U.S. regulatory pathways.
Because of our academic affiliation with the university, the vast majority of our pathologists and clinical laboratory scientists are faculty. We have a lot of expertise in rare diseases like Hemophilia A.
Looking Beyond AAV5 DetectCDxTM Test
Our success in developing a companion diagnostic test for ROCTAVIANTM shows pharmaceutical and biotechnology companies that PharmaDx at ARUP has all of the necessary elements in place to deliver on collaborations like this.
We are proud to serve patients, physicians, and our industry partners, while advancing gene therapy through diagnostic testing.
We plan to continue working in this space, developing companion diagnostic tests that will serve patients with other genetic conditions and helping to improve their health outcomes.
Jay Patel, MD
Jay L. Patel is vice president of Clinical Trials & PharmaDx at ARUP Laboratories and a professor of pathology at the Spencer Fox Eccles School of Medicine at the University of Utah. After receiving his MD from the University of Arizona, Patel completed a residency in anatomic and clinical pathology at the University of Utah. He then served as a hematopathology fellow at Stanford University. He is certified by the American Board of Pathology in anatomic and clinical pathology, with subspecialty boards in hematology. Patel’s clinical and research interests are broad and include all aspects of hematopathology. Currently, he is working on the application of next-generation sequencing technologies in the diagnosis and prognostication of hematolymphoid malignancies and benign hematologic disorders.