Effective Date

Date of Origin 

10-01-2025            

Pegasys^®*

(peginterferon alfa-2a)

Injection for subcutaneous use

Chronic hepatitis C:

• Adult patients: In combination with other hepatitis C virus (HCV) drugs for adults with compensated liver disease. Pegasys monotherapy is indicated only if patient has contraindication or significant intolerance to other HCV drugs
• Pediatric patients: In combination with ribavirin for pediatric patients 5 years of age and older with compensated liver disease 

Chronic hepatitis B:

Adult patients: Treatment of adults with HBeAg positive and HBeAg negative chronic hepatitis B (CHB) infection who have compensated liver disease and evidence of viral replication and liver inflammation

Pediatric patients: Treatment of non-cirrhotic, HBeAg-positive patients 3 years of age and older with HBeAg positive CHB and evidence of viral replication and elevations in serum alanine aminotransferase (ALT)

* For peg-interferons for Multiple sclerosis (e.g. Plegridy), refer to the Multiple Sclerosis PA/QL program

1

Hepatitis B

Hepatitis B is an infection of the liver caused by the Hepatitis B virus (HBV). The prevalence of chronic HBV infection is estimated at 240 million persons globally and 704,000 persons in the United States. Deaths due to cirrhosis and cancer secondary to chronic HBV infection are estimated at 310,000 and 340,000 per year respectively. The goal of treatment of chronic HBV infection is to decrease morbidity and mortality.(5)

The presence of hepatitis B surface antigen (HBsAg) establishes the diagnosis of hepatitis B. Chronic infection is defined by the presence of HBsAg for at least 6 months. HBV is transmitted by perinatal, percutaneous, and sexual exposure and by close person-to-person contact (presumably by open cuts and sores, especially among children in hyper pandemic areas). HBsAg and antibody to hepatitis B surface antigen (anti-HBs) should be used for screening and indication for immunization. Alternatively, antibody to hepatitis B core antigen (anti-HBc) can be utilized for screening as long as those who test positive are further tested for both HBsAg and anti-HBs to differentiate current infection from previous infection. HBC vaccination does not lead to anti-HBc positivity.(5)

There are several agents currently indicated for treatment of chronic HBV. They include adefovir, entecavir, lamivudine, peg-interferon-α-2a, peg-interferon-α-2b, telbivudine, tenofovir alafenamide, and tenofovir dipovoxil fumarate. AASLD prefers entecavir, peg-interferon-α-2a (in adults), peg-interferon-α-2b (in children), tenofovir alafenamide, and tenofovir dipovoxil fumarate as initial therapy for adults HBV infection.(5)

Hepatitis C(3,4)

Hepatitis C is an infection of the liver caused by the Hepatitis C virus (HCV), a blood-borne virus. Today, most people become infected with HCV by sharing needles or other equipment to inject drugs. Hepatitis C infection can either be acute or chronic. Acute HCV infection is defined as presenting within 6 months following exposure to the virus. In 2018, the reported acute hepatitis C case count in the United States corresponded to a rate of 1.2 cases per 100,000 population, an over 71% increase from the reported incidence rate in 2014. The infection is defined as chronic if the virus is present beyond 6 months following exposure. More than 50% of people who become infected with HCV develop chronic infection. Chronic hepatitis C is a serious disease that can result in cirrhosis, liver cancer, and death.(3,4)

The American Association for the Study of Liver diseases (AASLD) along with the Infectious Diseases society of America (IDSA) recommend the following:(2)

• One-time, routine, opt out HCV testing is recommended for all individuals aged 18 years and older
• One-time HCV testing should be performed for all persons less than 18 years old with activities, exposures, or conditions or circumstances associated with an increased risk of HCV infection
• Prenatal HCV testing as part of routine prenatal care is recommended with each pregnancy
• Periodic repeat HCV testing should be offered to all persons with activities, exposures, or conditions or circumstances associated with an increased risk of HCV exposure
• Annual HCV testing is recommended for all persons who inject drugs, for HIV-infected men who have unprotected sex with men, and men who have sex with men taking pre-exposure prophylaxis (PrEP)

Risk activities:

• Injection drug use (current or ever, including those who injected only once)
• Intranasal illicit drug use
• Use of glass crack pipes
• Male engagement in sex with men
• Engagement in chem sex (defined as the intentional combining of sex with the use of particular nonprescription [illicit] drugs in order to facilitate or enhance the sexual encounter)
• Risk exposures:
  • Persons on long-term hemodialysis (ever)
  • Persons with percutaneous/parenteral exposures in an unregulated setting
  • Healthcare, emergency medical, and public safety workers after needlestick, sharps, or mucosal exposure to HCV-infected blood
  • Children born to HCV-infected women
  • Recipients of a prior transfusion or organ transplant, including persons who:
    • Were notified that they received blood from a donor who later tested positive for HCV
    • Received a transfusion of blood or blood components, or underwent an organ transplant before July 1992
    • Received clotting factor concentrates produced before 1987
  • Persons who were ever incarcerated
• Other conditions and circumstances:
  • HIV infection or HBV infection
  • Sexually active persons about to start pre-exposure prophylaxis (PrEP) for HIV
  • Chronic liver disease and/or chronic hepatitis, including unexplained elevated alanine aminotransferase (ALT) levels
  • Solid organ donors (living and deceased) and solid organ transplant recipients

AASLD/IDSA guidelines on when and in whom to treat

The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma, by the achievement of virologic cure as evidenced by a sustained virologic response (SVR) (defined as the continued absence of detectable HCV RNA for at least 12 weeks after completion of therapy). According to the AASLD/IDSA guidelines, treatment is recommended for all patients with acute or chronic HCV infection, except those with short life expectancies that cannot be remediated by treating HCV, by transplantation, or by other directed therapy. Treatment should be initiated early because delaying therapy may decrease the benefits of SVR and increase the rates of liver-related mortality.(3)

National Comprehensive Cancer Network supported indications

Peginterferon alfa-2a is the only interferon (IFN) available for clinical use in the United States and it may be substituted for other IFN preparations. The National Comprehensive Cancer Network (NCCN) lists peginterferon as a Category 2A treatment for several indications (treatment lengths can be referenced within the studies NCCN used to support this level of evidence).(6)

Safety

Pegasys (peginterferon alfa-2a) has the following boxed warning:(1)

• May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and withdraw therapy with persistently severe or worsening signs
• or symptoms of the above disorders

Pegasys (peginterferon alfa-2a) is contraindicated in:(1)

• Autoimmune hepatitis
• Hepatic decompensation in patients with cirrhosis
• Use in neonates/infants 
• Known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction and anaphylaxis to alpha interferons or any component of the product

Additional contraindication for use with other HCV antiviral drugs:(1)

• Ribavirin is contraindicated in pregnant women and men whose female partners are pregnant

1

Pegasys prescribing information. pharmaand GmbH. December 2023.

2

Bohn JP, Neururer S, Pirklbauer M, Pircher A, Wolf D. Hairy Cell Leukemia Patients Have a Normal Life Expectancy - A 35-Year Single-Center Experience and Comparison with the General Population. Cancers. 2022;14(5):1242. doi:10.3390/cancers14051242

3

AASLD/IDSA HCV Guidance: Recommendations for Testing, Managing, and Testing Hepatitis C. Available at www.hcvguidelines.org.

4

Viral hepatitis surveillance reports. Viral Hepatitis. Published October 2, 2024. https://www.cdc.gov/hepatitis/php/statistics-surveillance/?CDC_AAref_Val=https://www.cdc.gov/hepatitis/statistics/index.htm

5

Terrault NA, Bzowej NH, Chang K, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2015;63(1):261-283. doi:10.1002/hep.28156

6

National Comprehensive Cancer Network (NCCN), NCCN Guidelines Primary Cutaneous Lymphomas. Version 1.2025.

Pegasys

peginterferon alfa-

180 MCG/0.5ML ; 180 MCG/ML

M ; N ; O ; Y

N

Pegasys

peginterferon alfa-

180 MCG/0.5ML ; 180 MCG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The patient has a diagnosis of chronic hepatitis B AND BOTH of the following:
      1. The chronic hepatitis B infection has been confirmed by serological markers AND
      2. The patient has not been administered peg-interferon for 48 weeks or longer for treatment of chronic hepatitis B OR
   2. The patient has a diagnosis of chronic hepatitis C genotype 1, 2, 3, or 4 AND the requested agent will be used in a treatment regimen AND length of therapy recommended for the patient’s genotype as noted in Table 1, 2, or 3 (FDA labeling) OR
   3. The patient has another FDA labeled indication for the requested agent and route of administration OR
   4. The patient has another non-oncology indication that is supported in compendia for the requested agent and route of administration OR
   5. The patient has an oncology indication that is supported in compendia for the requested agent and route of administration (i.e., indication must be supported in compendia by ALL requirements [e.g., performance status, disease severity, previous failures, monotherapy vs. combination therapy]) AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The requested quantity (dose) is within FDA labeled dosing or supported in compendia for the requested indication AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: NCCN 1 or 2a recommended use, AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval:

• Hepatitis B: Up to 48 weeks total length of treatment
• Hepatitis C: Up to the duration as determined in Table 1, 2, or 3
• All other indications: 12 months or for the duration supported in FDA labeling or compendia whichever is shorter

Table 1: Sovaldi + PEG + RBV Treatment Recommendations based on FDA approved  labeling

*Includes patients with HCV/HIV co-infection

Table 2: Pegasys + RBV Treatment Recommendations based on FDA labeling

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. ONE of the following:
   1. The patient has a diagnosis of chronic hepatitis B AND the patient has NOT been administered peg-interferon for 48 weeks or longer for treatment of chronic hepatitis B OR
   2. The patient has a diagnosis of chronic hepatitis C genotype 1, 2, 3, or 4 AND the patient did not complete the duration of therapy for the treatment regimen recommended for the patient’s genotype as noted in tables 1, 2, or 3 OR
   3. The patient has a diagnosis other than chronic hepatitis B or C AND has had clinical benefit with the requested agent AND
3. The requested quantity (dose) is within FDA labeled dosing or supported in compendia for the requested indication AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: NCCN 1 or 2a recommended use, AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval:

• Hepatitis B: Up to duration to complete 48 weeks total length of treatment  
• Hepatitis C: Up to the duration to complete the regimen as determined in Table 1, 2, or 3  
• All other indications: 12 months or for duration supported in FDA label or compendia whichever is shorter

Table 1: Sovaldi + PEG-IFN + RBV Treatment Recommendations based on FDA labeled labeling

*Includes patients with HCV/HIV co-infection

Table 2: Pegasys + RBV Treatment Recommendations based on FDA labeling