Etranacogene Dezaparvovec-drlb (Hemgenix)

Number: 1023

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 etranacogene dezaparvovec-drlb (Hemgenix) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of etranacogene dezaparvovec-drlb (Hemgenix) is required of all Aetna participating providers and members in applicable plan designs. For precertification of etranacogene dezaparvovec-drlb (Hemgenix), 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 etranacogene dezaparvovec-drlb (Hemgenix), 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 etranacogene dezaparvovec-drlb (Hemgenix) 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;
   2. Member meets both of the following:
      
      
      1. Member does not have a history of Factor IX inhibitors (e.g., 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 (e.g., 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 150 exposure days; and
   5. Member has uncontrolled disease while concurrently using Factor IX prophylactic therapy or has a contraindication to Factor IX prophylaxis. Uncontrolled disease is defined as one of the following:
      
      
      1. Member has a current or history of a life-threatening hemorrhage;
      2. Member has a history of repeated, serious spontaneous bleeding episodes; and
   6. Member has platelets greater than or equal to 50,000 cells/microL at baseline; and
   7. Member does not have alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (unless there is a diagnosis of Gilbert’s Syndrome and member is otherwise stable), and creatinine levels greater than 2 times the upper limit of normal (ULN); and
   8. 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
   9. Member has undergone a hepatic ultrasound and/or elastography to rule out radiological liver abnormalities and/or sustained liver enzyme elevations; and
   10. 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
   11. 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
   12. Member has not received Hemgenix or any other gene therapy previously; and
   13. Prophylactic use of Factor IX products will not be given after Hemgenix 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 Hemgenix-derived Factor IX activity is deemed insufficient for adequate hemostasis); and
   14. Provider attests that liver enzymes and Factor IX activity will be followed per the protocol outlined in the prescribing information following receipt of Hemgenix infusion.

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

3. Continuation of Therapy

   See Dosage and Administration information.

4. Related Policies

   1. CPB 0131 - Clotting Factors

Dosage and Administration

Etranacogene dezaparvovec-drlb is supplied as Hemgenix with a nominal concentration of 1 x 1013 genome copies (gc)/mL, and each vial contains an extractable volume of not less than 10 mL. It is provided in kits containing 10 to 48 single-use vials, each kit constituting a dosage unit based on the individual's body weight. Hemgenix is a suspension for single-use intravenous infusion only.

Hemophilia B

The recommended dose of Hemgenix is given as a single dose of 2 x 1013 genome copies (gc) per kilogram (kg) of body weight (or 2 mL/kg body weight). Hemgenix can be administered only once.

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

Source: CSL Behring, 2022

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
76700	Ultrasound, abdominal, real time with image documentation; complete
76705	Ultrasound, abdominal, real time with image documentation; limited (eg, single organ, quadrant, follow-up)
76981	Ultrasound, elastography; parenchyma (eg, organ)
80076	Hepatic function panel This panel must include the following: Albumin (82040) Bilirubin, total (82247) Bilirubin, direct (82248) Phosphatase, alkaline (84075) Protein, total (84155) Transferase, alanine amino (ALT) (SGPT) (84460) Transferase, aspartate amino (AST) (SGOT) (84450)
81238	F9 (coagulation factor IX) (eg, hemophilia B), full gene sequence
82040	Albumin; serum, plasma or whole blood
82042	Albumin; other source, quantitative, each specimen
82043	Albumin; urine (eg, microalbumin), quantitative
82044	Albumin; urine (eg, microalbumin), semiquantitative (eg, reagent strip assay)
82045	Albumin; ischemia modified
82247	Bilirubin; total
82248	Bilirubin; direct
82565	Creatinine; blood
82575	Creatinine; clearance
84075	Phosphatase, alkaline
84078	Phosphatase, alkaline; heat stable (total not included)
84080	Phosphatase, alkaline; isoenzymes
84450	Transferase; aspartate amino (AST) (SGOT)
84460	Transferase; alanine amino (ALT) (SGPT)
85032	Blood count; manual cell count (erythrocyte, leukocyte, or platelet) each
85049	Blood count; platelet, automated
85250	Clotting; factor IX (PTC or Christmas)
85335	Factor inhibitor test
85390	Fibrinolysins or coagulopathy screen, interpretation, and report
86361	T cells; absolute CD4 count
87536	Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, quantification, includes reverse transcription when performed
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:
J1411	Injection, etranacogene dezaparvovec-drlb, per therapeutic dose
Other HCPCS codes related to the CPB:
J7165	Injection, prothrombin complex concentrate, human-lans, per i.u. of factor ix activity
J7168	Prothrombin complex concentrate (human), kcentra, per i.u. of factor ix activity
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:
B16.0- B17.0	Acute hepatitis B
B17.10-B17.11	Acute hepatitis C
B17.8	Other specified acute viral hepatitis
B18.0	Chronic viral hepatitis B with delta-agent
B18.1	Chronic viral hepatitis B without delta-agent
B18.2	Chronic viral hepatitis C
B19.10-B19.11	Unspecified viral hepatitis B
B19.20-B19.21	Unspecified viral hepatitis C
B20	Human immunodeficiency virus [HIV] disease
D68.8	Other specified coagulation defects
E88.09	Other disorders of plasma-protein metabolism, not elsewhere classified
I85.00 - I85.11	Esophageal varices
K70.10	Alcoholic hepatitis without ascites
K70.11	Alcoholic hepatitis with ascites
K70.30	Alcoholic cirrhosis of liver without ascites
K71.50	Toxic liver disease with chronic active hepatitis without ascites
K71.51	Toxic liver disease with chronic active hepatitis with ascites
K72.90	Hepatic failure, unspecified without coma
K72.91	Hepatic failure, unspecified with coma
K76.82	Hepatic encephalopathy
K80.00-K83.09	Biliary disease
K87	Disorders of gallbladder, biliary tract and pancreas in diseases classified elsewhere
R17	Unspecified jaundice
R18.0-R18.8	Ascites
Z21	Asymptomatic human immunodeficiency virus [HIV] infection status

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Background

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

• Hemgenix is an adeno-associated virus vector-based gene therapy indicated for treatment of adults with 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.

Etranacogene dezaparvovec-drlb is available as Hemgenix (CSL Behring LLC) and is an adeno-associated virus serotype 5 (AAV5) based gene therapy developed to carry a copy of a gene encoding the Padua variant of human coagulation Factor IX (hFIX598 Padua). Cell transduction and an increase in circulating Factor IX activity occurs following the single intravenous infusion of Hemgenix (CSL Behring, 2022).

According to the prescribing information, Hemgenix carries the following warnings and precautions:

• Infusion reactions: Monitor during administration and for at least 3 hours after end of infusion. If symptoms occur, slow or interrupt administration. Re-start administration at a slower infusion once resolved.
• Hepatotoxicity: Closely monitor transaminase levels once per week for 3 months after Hemgenix administration to mitigate the risk of potential hepatotoxicity. Continue to monitor transaminases in all patients who developed liver enzyme elevations until liver enzymes return to baseline. Consider corticosteroid treatment should elevations occur.
• Hepatocellular carcinogenicity: For patients with preexisting risk factors (e.g., cirrhosis, advanced hepatic fibrosis, hepatitis B or C, non-alcoholic fatty liver disease (NAFLD), chronic alcohol consumption, non-alcoholic steatohepatitis (NASH), and advanced age), perform regular (e.g., annual) liver ultrasound and alpha-fetoprotein testing following administration.
• Monitoring laboratory tests: Monitor for Factor IX activity and Factor IX inhibitors.

Per the prescribing information, the most common adverse reactions (incidence ≥5%) were elevated ALT, headache, blood creatine kinase elevations, flu-like symptoms, infusion-related reactions, fatigue, malaise and elevated AST.

Refer to full prescribing information for Hemgenix 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, 2021).

On November 22, 2022, the U.S. Food and Drug Administration (FDA) approved Hemgenix (etranacogene dezaparvovec-drlb), an adeno-associated virus vector-based gene therapy for the treatment of adults with 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. The FDA approval was based on supporting data in two studies evaluating the safety and effectiveness of Hemgenix. These two studies consisted of 57 adult men(18 years to 75 years of age) with severe or moderately severe hemophilia B. In one study, a prospective, open-label, single-dose, single-arm, multi-national study, the individuals (n=54) with severe or moderately severe hemophilia B, received a single intravenous dose of 2 x 10¹³ gc/kg body weight of Hemgenix and entered a follow-up period of 5 years. Effectiveness was determined by decreases in the men's annualized bleeding rate (ABR). Individuals had increases in factor IX activity levels, a decreased need for routine factor IX replacement prophylaxis, and a 54% reduction in ABR compared to baseline (CSL Behring, 2022; FDA, 2022).

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References