Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Fidanacogene elaparvovec-dzkt (e.g., Beqvez)

Description:

Hemophilia B is a recessive X-linked congenital bleeding disorder that results from missing or insufficient levels of factor IX (FIX). The estimated prevalence of hemophilia B in the United States is 3.7 cases per 100,000 U.S. males. There are varying severities of hemophilia B depending on the level of FIX produced by the individual, but people with this condition are particularly vulnerable to bleeds in joints, muscles, and internal organs, which leads to pain, swelling, and joint damage.

Standard-of-care treatment for moderate to severe hemophilia consists of prophylaxis with FIX replacement therapy, which is self-administered intravenously (IV) multiple times a week and is aimed at preventing bleeds in order to prevent long-term adverse outcomes (e.g. degenerative joint disease, osteoarthritis). Generally, higher levels of FIX are associated with improved clinical outcomes and are required for individuals with joint-affected disease because it decreases the risk of bleeds and reduces long-term complications from bleeding. Approximately 3% of individuals with severe hemophilia B may develop an inhibitor to FIX replacement therapy (CDC, 2024), which can interfere with treatment. Individuals who develop inhibitors to FIX require treatment with higher doses of factor with or without bypassing agents (e.g., FEIBA, NovoSeven, SevenFact). Individuals with inhibitors are not eligible for gene therapy.

Fidanacogene elaparvovec-dzkt (e.g., Beqvez) z is an adenovirus-based gene therapy designed to introduce in the transduced cells a functional copy of the FIX gene encoding a high-activity FIX variant named FIX R338L, hFIX Padua. The AAVRh74var capsid is able to transduce hepatocytes, the natural site of FIX synthesis. Single intravenous (IV) infusion of Beqvez results in cell transduction and increase in circulating FIX activity in individuals with hemophilia B. Fidanacogene elaparvovec-dzkt (e.g., Beqvez) is the second gene therapy approved for the treatment of hemophilia B, following CSL Behring’s Etranacogene dezaparvovec-drlb (e.g., Hemgenix).

Regulatory Status

Fidanacogene elaparvovec-dzkt (e.g., Beqvez) was approved by the U.S. Food and Drug Administration (FDA) on April 25, 2024, for the treatment of moderate to severe hemophilia B 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.

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Prior Approval is required for Fidanacogene elaparvovec-dzkt (e.g., Beqvez).

The initial use of this drug requires documentation of direct physician involvement (MD/DO) in the ordering and evaluation, as well as signature, in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.

Approval timeframes may differ for members/participants of Self-Insured plans.

Effective September 18, 2024

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Fidanacogene elaparvovec-dzkt (e.g., Beqvez) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:

STANDARD REVIEW for up to 12 months:

1. Individual is 18 years of age or older (Beqvez, 2024); AND

2. Individual was assigned male at birth; AND

3. Individual has severe or moderately severe hemophilia B as defined by a plasma Factor IX (FIX) activity level less than or equal to 2%; AND

4. Individual meets one of the following:

a. Individual is currently receiving Factor IX (FIX) prophylaxis (e.g., AlphaNine SD, Alprolix, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine SD, Rebinyn, Rixubis); OR

b. Individual is using on demand therapy and has a documented history of at least 12 bleeding episodes over the previous year; AND

5. Individual meets one of the following:

a. Current or historical life-threatening hemorrhage; OR

b. Repeated, serious spontaneous bleeding episodes; AND

6. Individual does not have a history of FIX inhibitors or a positive screen result of greater than or equal to 0.6 Bethesda Units (BU) using the Nijmegen-Bethesda assay; AND

7. Individual is HIV negative or has a controlled HIV infection; AND

8. Individual does not have an active infection at time of scheduled infusion; AND

9. Individual has received a liver health assessment including enzyme testing and is absent of significant liver dysfunction or disease, defined as one or more of the following:

a. Liver cirrhosis of any etiology; OR

b. Active Hepatitis B or C infection; OR

c. Alanine transaminase (ALT) greater than or equal to 3 times the upper limit of normal; OR

d. Bilirubin greater than or equal to 3 times the upper limit of normal; OR

e. Alkaline phosphatase greater than or equal to 3 times the upper limit of normal; OR

f. International normalized ratio (INR) greater than or equal to 1.4; AND

10. Individual does not have a history of receiving gene therapy or under consideration for treatment for another gene therapy for hemophilia B; AND

11. Fidanacogene elaparvovec-dzkt (e.g., Beqvez) is being prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia B and is being administered by or in consultation with a Hemophilia Treatment Center (HTC) and post-administration monitoring per the manufacturer recommendations is planned by or in consultation with an HTC; AND

12. Must be dosed in accordance with the FDA label.

Policy Guidelines

For certain identified gene and cellular therapies such as Fidanacogene elaparvovec-dzkt (e.g., Beqvez), when coverage is available and the individual meets benefit certificate primary coverage criteria, distribution from a specialty pharmacy provider due to cost (distribution channel restriction) may be required in order for coverage to be provided.

Dosage and Administration

Dosing per FDA Guidelines

The recommended dose of fidanacogene elaparvovec-dzkt (e.g., Beqvez) is 5 × 100 billion vector genomes per kg (vg/kg) of body weight. Dose is based on adjusted body weight for those with a BMI larger than 30 kg/square meters.

Fidanacogene elaparvovec-dzkt (e.g., Beqvez) is available as a one-time single-dose intravenous infusion.

Fidanacogene elaparvovec-dzkt (e.g., Beqvez) should be administered as an intravenous infusion after dilution by a healthcare professional.

Dosing Limits

One injection per lifetime.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Fidanacogene elaparvovec-dzkt (e.g., Beqvez), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, fidanacogene elaparvovec-dzkt (e.g., Beqvez), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

The FDA approval of fidanacogene elaparvovec-dzkt (e.g., Beqvez) is based on results from the pivotal Phase 3 BENEGENE-2 (NCT03861273) study, an ongoing, prospective, open-label, single-arm, multinational trial. BENEGENE-2 met its primary endpoint of noninferiority in the 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 observed among patients who received Beqvez in the efficacy evaluation period (EEP) – defined as between Week 12 and the 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 6 months (median 1.2 years of follow-up). Bleeds were eliminated in 60% of patients compared to 29% in the prophylaxis arm. A median ABR of zero (range of 0 to 19) was observed during the EEP compared to the prophylaxis arm, in which a median ABR of 1.3 (range of 0 to 53.9) was observed. Clinical trial participants will be followed for up to a total of 15 years, including 6 years in the BENEGENE-2 study and an additional 9 years as part of a separate Phase 3 study (NCT05568719) to learn about the long-term safety and efficacy of fidanacogene elaparvovec-dzkt (e.g., Beqvez).

The safety of fidanacogene elaparvovec-dzkt (e.g., Beqvez) was evaluated in 60 patients (45 patients in Study 1 [NCT03861273] and 15 patients in Study 2 [NCT02484092]) who received the recommended dose (5 × 1011 vg/kg) in two open-label studies. No serious adverse reactions were reported in patients treated with Beqvez. No deaths, serious adverse events related to treatment or associated with infusion reactions, thrombotic events, or FIX inhibitors were reported. Elevated transaminases, which may indicate immune-mediated hepatotoxicity, were observed in 26 of 60 patients treated at the recommended dose and 31 of 60 patients received corticosteroids. There is no Risk Evaluation and Mitigation Strategy (REMS) program for Beqvez. Providers should monitor liver enzymes for hepatotoxicity and monitor FIX activity and inhibitors for treatment efficacy. Individuals may be treated with a course of corticosteroids if there is an elevation in liver enzymes or FIX decreases. Long-term corticosteroid use may be a concern for patients and providers. In patients with risk factors for hepatocellular carcinoma, regular liver ultrasound and alpha-fetoprotein testing should be performed.

CPT/HCPCS:

References:

Beqvez(2024) Package Insert New York, NY: Pfizer Inc.; April 2024.

Centers for Disease Control and Prevention (CDC).(2023) A new study of hemophilia occurrence finds many more cases in the United States. July 25, 2023. Accessed June 24, 2024. https://archive.cdc.gov/#/details?url=https://www.cdc.gov/ncbddd/hemophilia/features/keyfin ding-hemophilia-occurrence-US.html

ICER Institute for Clinical and Economic Review.(2023) Gene Therapy for Hemophilia B and An Update on Gene Therapy for Hemophilia A: Effectiveness and Value. Draft Evidence Report. September 13, 2022.

Medical and Scientific Advisory Committee.(2022) MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without inhibitors. MASAC Document #267. April 2022.

Medical and Scientific Advisory Council (MASAC)(2023) MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. Document #280. August 2023.

Pasi KJ, Rangarajan S, Mitchell N, et al.(2020) Multiyear Follow-up of AAV5- hFVIII-SQ Gene Therapy for Hemophilia A. N Engl J Med 2020; 382:29-40.

Soucie JM, et al.(2023) Occurrence rates of haemophilia among males in the United States based on surveillance conducted in specialized haemophilia treatment centres. Haemophilia 2020; 26:487- 93. doi:10.1111/hae.13998

Srivastave A, Santagostino E, Dougall A, et al.(2020) World Federation of Hemophilia Guidelines for the Management of Hemophilia. 3rd edition.

World Federation of Hemophilia.(2020) Guidelines for the management of hemophilia. Haemophilia. 2020 August 3. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.14046. Accessed on: June 24, 2024.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.