Hepatitis B is a viral infection that targets the liver, leading to either acute or chronic disease.

Acute infections are often self-limiting and do not always require treatment; however, a small fraction can progress to chronic hepatitis B. Chronic infections pose significant health risks as they can result in serious liver complications, such as cirrhosis and hepatocellular carcinoma.

Vemlidy (tenofovir alafenamide), granted FDA approval in 2016, is a nucleotide analog reverse transcriptase inhibitor employed to manage chronic hepatitis B infection in adults with compensated liver disease.

It shares a similar mechanism of action with tenofovir disoproxil fumarate (Viread), another variant of tenofovir used in managing chronic hepatitis B. Yet, Vemlidy is linked to fewer adverse effects on kidneys and bones, making it a preferable treatment option in certain patient populations.

In addition to its role in managing chronic hepatitis B, Vemlidy also has an important place in prophylaxis against hepatitis B virus reactivation in immunocompromised patients, and hepatitis B virus reinfection post liver transplant, further broadening its clinical utility.

Definitions

• Albumin is a type of protein made by the liver that often decreases with liver disease.
• Anti-CD20 Therapy is a type of drug that targets CD20, a protein found on the surface of B cells. It is used in certain types of cancers and autoimmune diseases.
• Antibody to Hepatitis B core Antigen (Anti-HBc) is an antibody that is part of the body's immune response to a hepatitis B infection.
• ARV Treatment Regimen refers to the use of Antiretroviral (ARV) medications, which are a class of drugs utilized in the management and treatment of Human Immunodeficiency Virus (HIV). A fully suppressive regimen is one that effectively minimizes the viral load in a patient's body to levels that are undetectable, thereby helping to prevent progression of the disease and transmission of the virus.
• Ascites refers to an abnormal buildup of fluid in the abdomen, often due to severe liver disease.
• Chronic Hepatitis B is a long-lasting infection of the liver caused by the hepatitis B virus, defined by the persistence of the virus for six months or more. It is typically diagnosed through detection of hepatitis B surface antigen (HBsAg) in the blood.
• Decompensated Liver Disease is a severe stage of chronic liver disease characterized by the presence of complications such as variceal bleeding, ascites, hepatic encephalopathy, or abnormal liver function tests. It indicates a failure of the liver to perform its normal metabolic and synthetic functions.
• Hepatitis B surface Antigen (HBsAg) is a surface antigen of the hepatitis B virus; its presence indicates active infection.
• Hepatic Encephalopathy is a decline in brain function that occurs as a result of severe liver disease. It can lead to symptoms like confusion and poor coordination.
• Hepatitis B Flare is a sudden increase in liver inflammation, typically measured by a rise in alanine aminotransferase (ALT) levels, in a person with chronic hepatitis B.
• Hepatitis B Virus Reactivation is a sudden increase in hepatitis B virus in the bloodstream, which can occur spontaneously or as a result of medical or immunological triggers.
• Direct-acting antivirals (DAAs) are a group of medications used to treat hepatitis C. They directly target the hepatitis C virus to stop it from making copies of itself.
• Immunosuppressive or Cytotoxic Therapy are treatments that reduce the activity of the body's immune system, often used in conditions like cancer and autoimmune diseases.
• International Normalized Ratio (INR) is a standardized measurement of the time it takes for blood to clot. It's used to monitor and adjust dosing of anticoagulant therapy.
• Lamivudine-resistance arises when the hepatitis B virus mutates after exposure to the antiviral drug lamivudine over a prolonged period.

These mutations enable the virus to resist the effects of the drug, leading to an increase in viral replication and potentially resulting in the failure of lamivudine treatment.

Prophylaxis is the prevention of disease. In this context, Vemlidy is being used to prevent the reactivation or reinfection of the hepatitis B virus.

Variceal Bleeding refers to bleeding from enlarged veins (varices) usually found in the esophagus or stomach. It is a serious complication of liver cirrhosis.

Medical Necessity Criteria for Initial Authorization

The Plan considers Vemlidy (tenofovir alafenamide) medically necessary when ALL the following criteria are met for the applicable indication listed below:

Treatment of chronic hepatitis B virus infection

1. The member is 12 years of age or older; AND
2. The member has a diagnosis of chronic hepatitis B confirmed by appropriate laboratory test; AND
3. The member has tested negative for HIV-1 virus; AND
4. The member meets ONE of the following conditions regarding previous therapies:
   • a. The member has been previously treated with lamivudine, or with a strain known to have lamivudine resistance variants; or
   • b. The member is unable to use, or has tried and failed entecavir; AND
5. The member does NOT have decompensated liver disease, demonstrated by meeting ALL of the following:
   • a. No variceal bleeding; and
   • b. No ascites; and
   • c. No hepatic encephalopathy; and
   • d. International normalized ratio (INR) less than 1.5x upper limit of normal (ULN); and
   • e. Total bilirubin less than 2.5x upper limit of normal (ULN); and
   • f. Albumin level greater than or equal to 3 g/dL; AND
6. Chart documentation and supporting laboratory work are provided for review to substantiate the above listed requirements.

Hepatitis B Virus Reactivation Prophylaxis

1. The member is 18 years of age or older; AND
2. Prescribed by or in consultation with an oncologist, gastroenterologist, hepatologist, infectious disease specialist, or transplant specialist; AND
3. Vemlidy is being used for prophylaxis against hepatitis B reactivation; AND
4. Information reviewed does not indicate ANY of the following:
   • a. The member is currently experiencing a Hepatitis B flare; or
   • b. The member has known contraindications to the use of Vemlidy; AND
5. The member fulfills ONE of the following conditions:
   • a. Is anti-HBc-positive, HBsAg-positive AND undergoing immunosuppressive or cytotoxic therapy; or
   • b. Is anti-HBc-positive, HBsAg-negative AND undergoing stem cell transplantation or receiving anti-CD20 therapy such as rituximab; AND
6. If coinfected with HIV or chronic HCV, the member meets ONE of the following:
   • a. The member has hepatitis B and HIV coinfection AND is receiving a fully suppressive ARV treatment regimen for HIV; or
   • b. The member is coinfected with hepatitis B and chronic HCV and is currently receiving a hepatitis C DAA therapy; AND
7. Chart documentation and supporting laboratory work are provided for review to substantiate the above listed requirements.

Hepatitis B Virus Reinfection Prophylaxis Post Liver Transplant

1. The member is 18 years of age or older; AND
2. Prescribed by or in consultation with a gastroenterologist, hepatologist, infectious disease specialist, or transplant specialist; AND
3. Vemlidy is being used for prophylaxis against HBV reinfection; AND
4. The member has a documented history of chronic Hepatitis B infection and has undergone a liver transplant; AND
5. If coinfected with HIV or chronic HCV, the member meets ONE of the following:
   • a. The member has hepatitis B and HIV coinfection AND is receiving a fully suppressive ARV treatment regimen for HIV; or
   • b. The member is coinfected with hepatitis B and chronic HCV and is currently receiving a hepatitis C DAA therapy; AND
6. The member does not have contraindications to Vemlidy; AND

Chart documentation and supporting laboratory work are provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, Vemlidy (tenofovir alafenamide) will be approved for 6 months.

Medical Necessity Criteria for Reauthorization

Reauthorization of 12 months will be granted if the following criteria are met:

For Treatment of Chronic Hepatitis B Virus Infection:

1. The member continues to meet all initial authorization criteria; AND
2. The member has documented clinical improvement, or maintenance, in disease activity, as evidenced by ANY of the following parameters:
   • a. Reduction in HBV DNA levels; or
   • b. Loss or reduction of HBeAg or HBsAg; or
   • c. Normalization of ALT levels; AND
3. Chart documentation and supporting laboratory work are provided for review to substantiate the above listed requirements.

For Hepatitis B Virus Reactivation Prophylaxis:

1. The member continues to meet all initial authorization criteria; AND
2. The member has no evidence of Hepatitis B reactivation; AND
3. If coinfected with HIV or chronic HCV, the member continues to receive an effective treatment regimen for these conditions; AND
4. Chart documentation and supporting laboratory work are provided for review to substantiate the above listed requirements.

For Hepatitis B Virus Reinfection Prophylaxis Post Liver Transplant:

1. The member continues to meet all initial authorization criteria; AND
2. The member shows no signs of Hepatitis B virus reinfection; AND
3. If coinfected with HIV or chronic HCV, the member continues to receive an effective treatment regimen for these conditions; AND
4. Chart documentation and supporting laboratory work are provided for review to substantiate the above listed requirements.

Experimental or Investigational / Not Medically Necessary

Vemlidy (tenofovir alafenamide) for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. A.S. Lok et al. Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology 2016; 63:284.
2. E. Murakami et al. Implications of efficient hepatic delivery by tenofovir alafenamide (GS-7340) for hepatitis B virus therapy. Antimicrob Agents Chemother 2015; 59:3563.
3. H.L.Y. Chan et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; 1:185.
4. K.K. Mugwanya et al. Pre-exposure prophylaxis use by breastfeeding HIV-uninfected women: a prospective short-term study of antiretroviral excretion in breast milk and infant absorption. PLoS Med 2016 September 27 (epub).
5. Kumar M, Satapathy S. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology. 2007;45(1):97.
6. M. Buti et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; 1:196.
7. N.A. Terrault et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016;63:261.
8. P. Martin et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2015 update. Clin Gastroenterol Hepatol 2015; 13:2071.
9. P.J. Ruane et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr 2013; 63:449.
10. Rashidi-Alavijeh J, Straub K, Achterfeld A, Wedemeyer H, Willuweit K, Herzer K. Safety and efficacy of tenofovir alafenamide in liver transplant recipients: a single center experience. Transpl Infect Dis. 2021;23(3):e13522. doi:10.1111/tid.135226
11. Terrault NA, Lok ASF, McMahon BJ, et al.

1. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.2980012.
2. Tran TT, Ahn J, Reau NS. ACG Clinical Guideline: Liver Disease and Pregnancy. Am J Gastroenterol. 2016;111(2):176-194. doi: 10.1038/ajg.2015.430.
3. Vemlidy (tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences Inc; October 2022.

Clinical Guideline Revision / History Information

Original Date: 08/06/2020
Reviewed/Revised: 06/24/2021, 12/01/2021, 06/23/2022, 06/29/2023