The FDA has approved Labcorp’s nAbCyte Anti-AAVRh74var HB-FE Assay, a cell-based companion diagnostic assay intended to detect the presence of antiAAVRh74var antibodies for the purpose of determining the eligibility of patients to receive Pfizer’s hemophilia B gene therapy fidanacogene elaparvovec-dzkt (marketed as Beqvez).1
Testing for the presence of neutralizing antibodies (nAbs) is an essential step before patients can receive Beqvez, which is indicated for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy; or who have a history of, or current, life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to the AAVRh74var capsid determined by an FDA-approved test.2 According to Labcorp, it is thought that the presence of nAbs could negatively impact the safety or efficacy of the gene therapy product.1
"At Labcorp, we are committed to advancing cell and gene therapy and driving innovation that assists clinicians in making well-informed treatment decisions," Brian Caveney, MD, Labcorp's president of Early Development Research Laboratories and chief medical and scientific officer, said in a statement.1 "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."
Key Takeaways
- The FDA has approved Labcorp’s nAbCyte Anti-AAVRh74var HB-FE Assay, a cell-based companion diagnostic assay intended to detect the presence of antiAAVRh74var antibodies for the purpose of determining the eligibility of patients to receive Pfizer’s hemophilia B gene therapy fidanacogene elaparvovec-dzkt (marketed as Beqvez).
- Testing for the presence of neutralizing antibodies (nAbs) is an essential step before patients can receive Beqvez, which is indicated for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy; or who have a history of, or current, life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to the AAVRh74var capsid determined by an FDA-approved test.
- According to Labcorp, it is thought that the presence of nAbs could negatively impact the safety or efficacy of the gene therapy product.
The nAbCyte test provides a qualitative result, with a negative result indicating the nonpresence of AAVRh74var nAbs and positive result indicating the presence of AAVRh74var nAbs. If a patient tests negative, they may be considered for treatment with Beqvez, provided their condition otherwise meets the gene therapy’s indication. Labcorp noted that nAbCyte, which the FDA has approved as a Humanitarian Use Device for utilization in the selection of patients for treatment with Beqvez, has not had its efficacy for this purpose demonstrated.
"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, thehead of US Specialty Care Medical Affairs at Pfizer, added to the statement.1 "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 was approved for its current indication by the FDA on April 26, 2024.2 It is an adeno-associated virus (AAV) vector-based gene therapy that works by introducing a functional copy of the factor IX (FIX) gene encoding a high-activity FIX variant via transduced cells. The one-time therapy was also recently approved in Canada, in January 2024,3 and is currently under review with the European Medicines Agency, according to Pfizer.
Notably, a different companion diagnostic assay, ARUP Laboratories’ AAV5 DetectCDx, was previously approved by the FDA for the purpose of determining the eligibility of patients who are considering treatment with BioMarin’s hemophilia A gene therapy valoctocogene roxaparvovec (val-rox; marketed as Roctavian).4 AAV5 DetectCDx, which received approval from the FDA simultaneously with val-rox itself, on June 29, 2023, utilizes electrochemiluminescence to detect antiAAV5 antibodies in samples of patients’ plasma. In the United States, ARUP Laboratories is providing all laboratory testing services for AAV5 DetectCDx, which was the first companion diagnostic immunoassay for a gene therapy to have been approved by the FDA.
REFERENCES
1. Labcorp receives FDA approval for first companion diagnostic for use with Pfizer's newly approved gene therapy to treat patients with hemophilia B. News release. Labcorp. April 29, 2024. Accessed May 2, 2024. https://www.labcorp.com/labcorp-receives-fda-approval-first-companion-diagnostic-use-pfizers-newly-approved-gene-therapy
2. U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. News release. Pfizer. April 26, 2024. Accessed April 26, 2024. https://www.businesswire.com/news/home/20240425269649/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BEQVEZ%E2%84%A2-fidanacogene-elaparvovec-dzkt-a-One-Time-Gene-Therapy-for-Adults-with-Hemophilia-B
3. Health Canada approves Pfizer Canada's gene therapy in hemophilia B. News release. Pfizer Canada. January 3, 2024. Accessed April 26, 2024. https://www.newswire.ca/news-releases/health-canada-approves-pfizer-canada-s-gene-therapy-in-hemophilia-b-841249479.html
4. FDA approves ARUP Laboratories’ AAV5 DetectCDx, a first-ever companion diagnostic immunoassay for a gene therapy. News release. ARUP Laboratories. June 29, 2023. Accessed July 13, 2023. https://www.aruplab.com/news/06-29-2023/fda-approves-arup-laboratories-aav5-detectcdxtm
