Fidanacogene Elaparvovec-dzkt (Beqvez)

Number: 1060

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresses fidanacogene elaparvovec-dzkt (Beqvez) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of fidanacogene elaparvovec-dzkt (Beqvez) is required of all Aetna participating providers and members in applicable plan designs. For precertification of fidanacogene elaparvovec-dzkt (Beqvez), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

Note: Unless member's health plan has elected not to require, gene and cellular therapies must be administered at an Aetna Institutes® Gene Based, Cellular and Other Innovative Therapy (GCIT®) Network. For fidanacogene elaparvovec-dzkt (Beqvez), see Aetna Institutes® GCIT Designated Centers. 

  1. Prescriber Specialties

    This medication must be prescribed by or in consultation with a hematologist.

  2. Criteria for Initial Approval

    Hemophilia B

    Aetna considers fidanacogene elaparvovec-dzkt (Beqvez) medically necessary for one dose total for the treatment of hemophilia B (congenital factor IX deficiency) when all of the following criteria are met:

    1. Member is 18 years of age or older; and
    2. Member meets both of the following:

      1. Member does not have a history of Factor IX inhibitors (greater than or equal to 0.6 Bethesda units [BU]); and
      2. Member has a negative Factor IX inhibitor test result within the past 30 days (less than 0.6 Bethesda units[BU]); and
    3. Member has severe or moderately severe Factor IX deficiency (less than or equal to 2% of normal circulating Factor IX); and
    4. Member has a history of prophylactic Factor IX (e.g., Alprolix, Ixinity, Rebinyn) use for at least 50 exposure days; and
    5. Member has uncontrolled disease while currently using Factor IX prophylactic therapy or has a contraindication to receiving Factor IX prophylaxis. Uncontrolled disease is defined as one of the following:

      1. Member has a current or history of a life-threatening hemorrhage; or
      2. Member has a history of repeated, serious spontaneous bleeding episodes; and
    6. Member has a negative adeno-associated virus serotype Rh74var (AAVRh74var) antibody test result; and
    7. Member has the following laboratory values at baseline:

      1. Hemoglobin greater than or equal to 11 g/dL; and
      2. Platelets greater than or equal to 100,000 cells/microL; and
      3. Creatinine less than or equal to 2.0 mg/dL; and
    8. Member does not have alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels greater than 2 times the upper limit of normal (ULN); and
    9. Member does not have a bilirubin level greater than 1.5 times the ULN (unless there is a diagnosis of Gilbert’s Syndrome and member is otherwise stable); and
    10. Member does not have current unstable liver or biliary disease as defined by the presence of ascites, hepatic encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis; and
    11. Member has undergone a hepatic ultrasound and/or elastography to rule out radiological liver abnormalities and/or sustained liver enzyme elevations; and
    12. Member does not have cirrhosis or stage 3 or 4 liver fibrosis; and
    13. Member meets both of the following:

      1. Member does not have an active infection with hepatitis B virus or hepatitis C virus; and
      2. Member is not currently receiving antiviral therapy for a prior hepatitis B virus or hepatitis C virus exposure; and
    14. Member does not have uncontrolled human immunodeficiency virus (HIV) infection as defined as a CD4 cell count less than or equal to 200 mm3 or viral load greater than 20 copies/mL; and
    15. Member has not received Beqvez or any other gene therapy previously; and
    16. Prophylactic use of Factor IX products will not be given after Beqvez administration once adequate Factor IX levels have been achieved (Note: Factor IX therapy may be given in case of surgery, invasive procedures, trauma, or bleeds in the event that Beqvez-derived Factor IX activity is deemed insufficient for adequate hemostasis); and
    17. Provider attests that liver enzymes and Factor IX activity will be followed per the protocol outlined in the prescribing information following receipt of Beqvez infusion.

    Aetna considers all other indications as experimental, investigational, or unproven.

  3. Continuation of Therapy

    See Dosage and Administration section.

  4. Related Policies

Dosage and Administration

Fidanacogene elaparvovec-dzkt is supplied as Beqvez suspension for for intravenous infusion after dilution. Beqvez has a nominal concentration of 1 × 1013 vector genomes/mL (vg/mL), and each vial contains an extractable volume of 1 mL. The total number of vials will be customized to meet dosing requirements for individual persons based on their weight.

Beqvez is administered for a one-time single-dose intravenous infusion only.

The recommended dosage for Beqvez for the treatment of adults with moderate to sever hemophilia B (congenital factor IX deficiency) includes the following:

  • Perform baseline testing to select patients, including testing for pre-existing antibodies to AAVRh74var, factor IX inhibitor presence, and liver health tests.
  • The recommended dose of Beqvez is 5 × 1011 vector genomes per kg (vg/kg) of body weight. Dose based on adjusted body weight for those with a BMI > 30 kg/m2.
  • Administer Beqvez as an intravenous infusion after dilution in 0.9% sodium chloride with 0.25% human serum albumin (HSA) with a final volume of 200 mL over approximately 60 minutes.

Refer to full prescribing information for Beqvez for preparation and administration instructions.

Source: Pfizer, 2024

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

Other CPT codes related to the CPB:
76705 Ultrasound, abdominal, real time with image documentation; limited (eg, single organ, quadrant, follow-up) [Liver]
82247 Bilirubin; total
82248 Bilirubin; direct
82565 Creatinine; blood
82570 Creatinine; other source
82977 Glutamyltransferase, gamma (GGT
84075 Phosphatase, alkaline
84450 Transferase; aspartate amino (AST) (SGOT)
84460 Transferase; alanine amino (ALT) (SGPT)
85018 Blood count; hemoglobin (Hgb)
85049 Blood count; platelet, automated
85250 Clotting; factor IX (PTC or Christmas)
85335 Factor inhibitor test
85610 Prothrombin time
88720 Bilirubin, total, transcutaneous
91200 Liver elastography, mechanically induced shear wave (eg, vibration), without imaging, with interpretation and report
96365 - 96368 Intravenous infusion

HCPCS codes covered if selection criteria are met:
J1414 Injection, fidanacogene elaparvovec-dzkt, per therapeutic dose

Other HCPCS codes related to the CPB:
J7193 Factor ix (antihemophilic factor, purified, non-recombinant) per i.u
J7194 Factor ix, complex, per i.u
J7195 Injection, factor ix (antihemophilic factor, recombinant) per iu, not otherwise specified
J7200 Injection, factor ix, (antihemophilic factor, recombinant), rixubis, per iu
J7201 Injection, factor ix, fc fusion protein, (recombinant), alprolix, 1 i.u
J7202 Injection, factor ix, albumin fusion protein, (recombinant), idelvion, 1 i.u
J7203 Injection factor ix, (antihemophilic factor, recombinant), glycopegylated, (rebinyn), 1 iu
J7213 Injection, coagulation factor ix (recombinant), ixinity, 1 i.u

ICD-10 codes covered if selection criteria are met::
D67 Hereditary factor IX deficiency

ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
B16.0 – B16.9 Acute hepatitis B
B17.0 Acute delta-(super) infection of hepatitis B carrier
B17.10 – B17.11 Acute hepatitis C
B17.8 Other specified acute viral hepatitis
B17.9 Acute viral hepatitis, unspecified
B18.0 – B18.9 Chronic viral hepatitis
D68.8 Other specified coagulation defects [coagulopathy]
E88.09 Other disorders of plasma-protein metabolism, not elsewhere classified [hypoalbuminemia]
I85.00 – I85.11 Esophageal varices
I86.4 Gastric varices
K74.02 Hepatic fibrosis, advanced fibrosis [stage 3 or 4]
K74.60 – K74.69 Other and unspecified cirrhosis of liver
K76.82 Hepatic encephalopathy
R17 Unspecified jaundice [persistent]
R18.0 – R18.8 Ascites

Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

  • Beqvez is an adeno-associated virus vector-based gene therapy indicated for treatment of adults with moderate to severe Hemophilia B (congenital Factor IX deficiency) who:

    • Currently use Factor IX prophylaxis therapy; or
    • Have current or historical life-threatening hemorrhage; or
    • Have repeated, serious spontaneous bleeding episodes; and
    • Do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test.

Fidanacogene elaparvovec-dzkt is available as Beqvez (Pfizer Inc.) which is an adeno-associated virus (AAV)-based gene therapy for intravenous infusion. Beqvez is based on recombinant DNA technology that consists of a recombinant viral capsid (AAVRh74var) derived from a naturally occurring AAV serotype (Rh74) vector containing the human coagulation factor IX (FIX) transgene modified to a high-specific factor IX activity variant known as FIX-R338L. The AAVRh74var capsid is derived from the Rh74 AAV, which is not known to cause disease in humans. As a gene therapy, Beqvez is designed to introduce in the transduced cells a functional copy of the factor IX gene encoding a high-activity FIX variant (FIX-R338L, hFIX Padua). The AAVRh74var capsid is able to transduce hepatocytes, the natural site of factor IX synthesis. Beqvez single intravenous infusion results in cell transduction and increase in circulating factor IX activity in patients with hemophilia B (Pfizer, 2024a).

The Beqvez prescribing information notes the following warnings and precautions:

  • Hepatotoxicity: Monitor transaminases and factor IX activity levels once or twice weekly for at least 4 months after Beqvez administration to mitigate the risk of potential hepatotoxicity. Consider corticosteroid treatment for transaminase elevation or a decline in factor IX activity.
  • Infusion Reactions: Monitor during administration and for at least 3 hours after end of infusion. If symptoms occur, slow or stop administration. Restart infusion at a slower rate once reaction has resolved.
  • Malignancy: Monitor patients with risk factors for hepatocellular carcinoma (e.g., hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age) with regular liver ultrasound (e.g., annually) and alpha-fetoprotein testing for 5 years following administration. In the event that a malignancy occurs after treatment with Beqvez, contact the manufacturer.
  • Monitoring laboratory tests: Monitor for factor IX activity and factor IX inhibitors.

The Beqvez prescribing information notes the most common adverse reaction (incidence ≥5%) was an increase in transaminases.

Refer to full prescribing information for Beqvez for use in specific populations.

Hemophilia B is a rare genetic bleeding disorder afflicting individuals who have inadequate levels of factor IX, a blood protein. Factor IX, a clotting factor, is a specialized protein necessary for blood clotting, a process where blood seals a wound to stop bleeding and facilitate healing. Individuals with hemophilia B experience prolonged bleeding in comparison to unaffected individuals. Hemophilia B is caused by mutations in the factor IX (F9) gene on the X chromosome, and therefore, is inherited as an X-linked recessive trait. Hemophilia B has an estimated occurrence of 1 in 25,000 male births and is less prevalent than hemophilia A with an estimated occurrence of 1 in 5,000 male births. Typically, female carriers of hemophilia B do not have symptoms, however, approximately 10-25% will develop mild symptoms and may even report moderate and severe symptoms. The disease is classified as mild (e.g., bruising and bleeding after surgery, dental procedures, injury, or trauma), moderate (e.g., occasional episodes of spontaneous bleeding from deep tissues such as joints and muscles), or severe (e.g., frequent, spontaneous bleeding episodes) dependent upon the activity level of factor IX. Individuals with mild hemophilia have factor IX levels between 5 and 40% of normal; moderate hemophilia have factor levels from 1 to 5% of normal; and severe hemophilia have factor levels less than 1% of normal. Diagnosis of hemophilia B is based on the individual's personal history of bleeding, individual's family history of bleeding and inheritance, and laboratory testing. The initial test is the activated partial thromboplastin time (aPTT). Dependent upon aPTT test results, more specific blood testing is performed to determine if the cause of the abnormal aPTT is due to a deficiency of factor IX/hemophilia B, factor VIII/hemophilia A or another clotting factor. Once a diagnosis of hemophilia B is made, then the specific mutation in the F9 gene responsible for causing hemophilia may be identified. Current treatment options for individuals with hemophilia B include: recombinant factor IX, plasma-derived factor IX concentrates, and fresh frozen plasma (NORD, 2023).

On April 26, 2024, the U.S. Food and Drug Administration (FDA) approved fidanacogene elaparvovec-dzkt (Beqvez) for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test. The FDA approval was based on supporting data from the BENEGENE-2 study, an ongoing, prospective, open-label, single-arm, multi-national study evaluating the efficacy of Beqvez in 45 adult male participants with moderately severe to severe hemophilia B (factor IX activity ≤2 IU/dL) (Pfizer, 2024a; 2024b).

Eligible study participants, which included only participants who were negative for pre-existing neutralizing antibodies to AAVRh74var capsid, have completed a minimum of six months of routine FIX prophylaxis therapy during the lead-in study and received a single intravenous infusion dose of Beqvez at 5 x 1011 vg/kg of body weight (Pfizer, 2024a).

The BENEGENE-2 study met its primary endpoint of non-inferiority in the annualized bleeding rate (ABR) of total bleeds post-Beqvez infusion versus prophylaxis regimen with FIX, administered as part of usual care. A mean ABR of 2.5 was noted in among participants who received Beqvez in the efficacy evaluation period - defined as between week 12 and data cutoff (median 1.8 years of follow-up) - after receiving the one-time dose compared to a mean ABR of 4.5 during the lead-in pre-treatment period of at least six months (median 1.2 years of follow-up). Participants without bleeds was 60% for post-Beqvez period compared to 29% for the prophylaxis regimen with FIX in the lead-in period. A median ABR of zero (range 0 to 19) was noted during the Beqvez efficacy evaluation period compared to the prophylaxis lead-in period in which a median ABR of 1.3 (range of 0 to 53.9) was noted (Pfizer, 2024a; 2024b).

References

The above policy is based on the following references:

  1. National Organization for Rare Disorders (NORD). Hemophilia B. Danbury, CT: NORD. 2023. Available at: https://rarediseases.org/rare-diseases/hemophilia-b/. Accessed May 22, 2024.
  2. Pfizer Inc. Beqvez (fidanacogene elaparvovec-dzkt) injection, for intravenous infusion. Prescribing Information. New York, NY: Pfizer; revised April 2024a.
  3. Pfizer Inc. U.S. FDA approves Pfizer's Beqvez (fidanacogene elaparvovec-dzkt), a one-time gene therapy for adults with hemophilia B. Press Release. New York, NY: Pfizer; April 26, 2024b.