Fidanacogene Elaparvovec-dzkt (Beqvez)

Number: 1060

Table Of Contents

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

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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 when all of the following criteria are met:

   1. Member is 18 years of age or older; and
   2. Member meets either of the following:
      
      
      1. Member has a negative Factor IX inhibitor test result within the past 30 days; or
      2. If member has a positive Factor IX inhibitor test result within the past 30 days, there must be a negative test result within 2 weeks of the initial positive result; and

   3. Member has severe or moderately severe Factor IX deficiency (less than or equal to 2% of normal circulating Factor IX) and meets any of the following: 

      1. Member is currently using Factor IX prophylactic therapy; or
      2. Member has a current or history of a life-threatening hemorrhage; or
      3. Member has a history of repeated, serious spontaneous bleeding episodes; and
   4. Member has a negative adeno-associated virus serotype Rh74var (AAVRh74var) antibody test result; and
   5. Member has not previously received gene therapy treatment.

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

3. Continuation of Therapy

   See Dosage and Administration section.

4. Related Policies

• • CPB 1023 - Etranacogene Dezaparvovec-drlb (Hemgenix)

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

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
85250	Clotting; factor IX (PTC or Christmas)
85335	Factor inhibitor test
96365 - 96368	Intravenous infusion
HCPCS codes covered if selection criteria are met:
C9172	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
ICD-10 codes covered if selection criteria are met::
D67	Hereditary factor IX deficiency

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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).

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References