FDA OK’s virus antibody test to determine Beqvez eligibility

The gene therapy was recently approved to treat hemophilia B

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) has approved Labcorp’s companion diagnostic test for detecting preexisting antibodies against the viral carrier that’s used in Beqvez (fidanacogene elaparvovec-dzkt), Pfizer’s recently approved gene therapy for hemophilia B.

A negative result on an FDA-cleared test is needed to be eligible for Beqvez since the antibodies could render it less effective or safe. Called the nAbCyte Anti-AAVRh74var HB-FE Assay, the test from Labcorp is the first to be approved for this purpose.

“The approval of the nAbCyte companion diagnostic represents a first for a gene therapy that treats eligible patients with hemophilia B, helping to bring clarity to physicians and patients who are considering Beqvez as a treatment option,” Sonal Bhatia, MD, head of U.S. specialty care medical affairs at Pfizer, said in a press release. “We believe this companion diagnostic is an important tool for evaluating patients who may be suitable for gene therapy as the treatment paradigm advances with the introduction of gene therapies like Beqvez.”

Beqvez delivers a healthy copy of F9 — the gene that’s faulty in hemophilia B — to liver cells. This enables patients to produce their own working version of factor IX (FIX), the blood clotting protein they lack.

Gene therapies are commonly packaged into viral carriers, or vectors, that help them be more easily taken up by a person’s cells. Adeno-associated viruses (AAVs) are commonly used for this purpose because they generally don’t cause disease in humans and are easy to manipulate in the lab.

All three approved gene therapies for hemophilia — Beqvez and Hemgenix for hemophilia B, and Roctavian for hemophilia A — use some type of AAV carrier. In Beqvez, an engineered vector called AAVRh74var that’s derived from a naturally occurring AAV serotype called Rh74 AAV is used.

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Determining eligibility for Beqvez

People are often exposed to AAVs in the natural environment. While they usually don’t cause illness, they can prompt the immune system to produce antibodies against them. Up to 60% of people might have preexisting antibodies against AAVs, according to LabCorp.

If the immune system is already primed with antibodies to fight off an AAV that’s used to package a gene therapy, it could make the treatment less effective or safe. For this reason, it’s standard practice to rule out the presence of preexisting antibodies when determining a person’s eligibility for treatment.

The prescribing label for Beqvez stipulates that the presence of neutralizing antibodies against the therapy’s viral vector must be ruled out with an FDA-approved companion diagnostic test before a person can receive the one-time therapy.

Labcorp’s new test enables such antibodies to be detected. The results are delivered qualitatively as a simple negative or positive. If the test is negative, a patient who meets other eligibility criteria can be considered for treatment. If it’s positive, a person is ineligible.

“Labcorp is proud to offer the first cell-based, companion diagnostic to receive FDA approval, which represents a pioneering breakthrough in the field of companion diagnostics and will help transform the therapeutic landscape and the lives of patients living with rare, genetically inherited conditions,” said Brian Caveney, MD, Labcorp’s chief medical and scientific officer and president of early development research laboratories.

Before receiving Beqvez, patients must also test negative for neutralizing antibodies, or inhibitors, against FIX, as well as active HIV infection, and undergo liver health assessments to rule out certain liver conditions.