Hemophilia B Gene Therapies (BEQVEZ, HEMGENIX)

Hemophilia B Gene Therapies (BEQVEZ, HEMGENIX)

Office-Administration – intravenous (IV) infusion

Diagnosis considered for coverage:

Hemgenix:

Hemophilia B: Indicated for treatment of adults with Hemophilia B (congenital Factor IX deficiency) who currently use Factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.

Beqvez:

Hemophilia B: Indicated for the 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. Select patients for therapy based on an FDA-approved companion diagnostic for Beqvez. 

Coverage Criteria:

Hemgenix:

For diagnosis of Hemophilia B (congenital Factor IX deficiency):

• Documented diagnosis of Hemophilia B (congenital Factor IX deficiency); AND
• Patient is 18 years of age or older; AND
• Prescribed by or in consultation with a hematologist at a Hemophilia Treatment Center (HTC); AND
• Submission of medical records (e.g., chart notes) documenting ONE of the following:
  • Both of the following:
    • Diagnosis of severe hemophilia B
    • Documentation of endogenous Factor IX levels less than 1% of normal Factor IX (< 0.01 IU/mL)
  • All of the following:
    • Diagnosis of moderately severe hemophilia B
    • Documentation of endogenous Factor IX levels greater than or equal to 1% to less than or equal to 2% (greater than or equal to 0.01 IU/mL to less than or equal to 0.02 IU/mL)
    • Patient has current or historical life-threatening hemorrhage or repeated, serious spontaneous bleeding episodes; AND
• Paid claims or submission of medical records (e.g., chart notes) confirming that the patient is currently using Factor IX prophylaxis therapy (e.g., Alprolix, BeneFIX, Idelvion, Ixinity, Rebinyn, Rixubis, Mononine, etc.) and will discontinue treatment after stable on Hemgenix therapy; AND
• Patient has greater than 150 previous exposure days of treatment with a Factor IX agent; AND
• Submission of medical records (e.g., chart notes) documenting that the patient does not have any of the following:
  • Positive human immunodeficiency virus (HIV) test at screening that is not controlled with anti-viral therapy
  • Active infection with hepatitis B or C virus
  • Currently on antiviral treatment for hepatitis B or C
  • Positive Factor IX inhibitor titer test prior to therapy
  • History of Factor IX inhibitor
  • Anti-AAV antibody (e.g., AAV-5) titers exceeding 1:678; AND
• Submission of medical records (e.g., chart notes) documenting that the following laboratory values have been checked prior to therapy and are less than two times the upper limit of normal:
  • Alanine aminotransferase (ALT)
  • Alkaline phosphatase (ALP)
  • Aspartate aminotransferase (AST)
  • Total bilirubin; AND
• Submission of medical records (e.g., chart notes) documenting that hepatic ultrasound and elastography have been completed prior to therapy; AND
• Patient has never received any previous Hemophilia B gene therapy treatment in their lifetime (e.g., Hemgenix, Beqvez)

Beqvez:

For diagnosis of Hemophilia B:

• Diagnosis of Hemophilia B (congenital Factor IX deficiency), AND
• One of the following: 
  • Both of the following: 
    • Diagnosis of severe hemophilia B 
    • Documentation of endogenous Factor IX levels less than 1% of normal Factor IX (< 0.01 IU/mL), OR
  • All of the following: 
    • Diagnosis of moderately severe hemophilia B 
    • Documentation of endogenous Factor IX levels greater than or equal to 1% to less than or equal to 2% (greater than or equal to 0.01 IU/mL to less than or equal to 0.02 IU/mL)
    • Patient has current or historical life-threatening hemorrhage or repeated, serious spontaneous bleeding episodes; AND
• Patient is currently using Factor IX prophylaxis therapy (e.g., BeneFIX, Ixinity, Rixubis, etc.) and will discontinue treatment after stable on Hemgenix therapy; AND
• Both of the following:
  • Patient has been on prophylactic Factor IX replacement therapy for at least 6 months
  • Patient has greater than 50 previous exposure days of treatment with a Factor IX agent; AND
• Patient is 18 years of age or older; AND
• Patient does not have any of the following: 
  • Positive human immunodeficiency virus (HIV) test at screening that is not controlled with anti-viral therapy
  • Active infection with hepatitis B or C virus 
  • Currently on antiviral treatment for hepatitis B or C 
  • Positive Factor IX inhibitor titer test prior to therapy 
  • History of Factor IX inhibitor 
  • Anti-AAVRh74var neutralizing antibodies (nAB); AND 
• Provider attests that the following laboratory values have been checked prior to therapy and are less than two times the upper limit of normal: 
  • Alanine aminotransferase (ALT) 
  • Alkaline phosphatase (ALP) 
  • Aspartate aminotransferase (AST) 
  • Total bilirubin; AND
• Provider attests that hepatic ultrasound and elastography have been completed prior to therapy; AND
• Prescribed by a hematologist at a Hemophilia Treatment Center (HTC); AND
• Patient has never received any previous Hemophilia B gene therapy treatment in their lifetime (e.g., Hemgenix, Beqvez)

Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:

• For one-time single-dose intravenous infusion only.
• HEMGENIX (etranacogene dezaparvovec-drlb) is an adeno-associated viral vector-based gene therapy for intravenous infusion after dilution. HEMGENIX is a non-replicating recombinant adeno-associated virus serotype 5 (AAV5) containing a codon-optimized DNA sequence of the gain-of-function Padua variant R338L of human Factor IX (hFIX-Padua), under control of a liver-specific promotor 1 (LP1).
• BEQVEZ (fidanacogene elaparvovec-dzkt) 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.

Policy Review History:

• 06/01/2023 - New criteria for utilization management program approved by WHA P&T (05/16/2023).
• 12/1/2024 (policy effective date)- Addition of Beqvez to guideline and updated Hemgenix criteria to state "Patient has never received any previous Hemophilia B gene therapy treatment in their lifetime (e.g., Hemgenix, Beqvez)"  (P&T 11/20/2024) (P&T Meeting November)

References:

1. Hemgenix Prescribing Information. CSL Behring LLC. King of Prussia, PA. November 2022.
2. CSL Behring. Phase III, Open-label, Single-dose, Multi-center, Multinational Trial Investigating a Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, AMT-061) Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B. clinicaltrials.gov. Published September 26, 2022. Accessed January 11, 2023. https://clinicaltrials.gov/ct2/show/study/NCT03569891
3. Beqvez Prescribing Information. Pfizer Inc. New York, NY. April 2024.