Prior Auth Protocol

FDA Approved Indications:

Treatment of Chronic Hepatitis C (CHC) as part of a combination regimen with other hepatitis C virus (HCV) antiviral drugs in patients 5 years of age and older with compensated liver disease
Monotherapy is indicated for:

CHC only if patient has contraindication to or significant intolerance to other HCV antiviral drugs
Treatment of adult patients with HBeAg positive or HBeAg negative chronic hepatitis B infection who have compensated liver disease and evidence of viral replication and liver inflammation.

Health Net Approved Indications and Usage Guidelines:

CHRONIC HEPATITIS C

For all patients

Patient is 5 years of age or older
Must be used in combination with ribavirin unless the patient is intolerant to ribavirin or has a contraindication to ribavirin

AND

For previously untreated patients (naive patients)

Diagnosis of chronic hepatitis C confirmed by detectable serum HCV RNA by quantitative assay. Baseline viral load by quantitative assay and genotype are required to determine length of approval and future virologic response.

AND

Three consecutive elevated (>2x ULN) transaminases (ALT) at least one month apart (not required for gentoype 2 or 3)

OR

Liver biopsy showing greater than grade 1, stage 1 damage (Stage 3-4 portal or bridging fibrosis, moderate/severe inflammation or necrosis as documented by a Metavir score of greater than or equal to 2, Ishak score of greater than or equal to 3, or necroinflammation (Grade 9-18)). Biopsy results are not needed for genotypes 2 or 3.

OR

In combination with ribavirin if patient has experienced a relapse after a liver transplantation regardless of prior regimen

OR

Patient has symptomatic cryoglobulinemia

Non-responders

In combination with ribavirin if patient has had no prior combination therapy with pegylated interferon and ribavirin

OR

In combination with ribavirin if patient was a non-responder to the combination of pegylated interferon and ribavirin

Relapsers

In combination with ribavirin if a patient had an undetectable HCV-RNA level at any time while on treatment for chronic hepatitis C, then developed detectable HCV-RNA levels

Definitions:
Non-responder	Patient never achieved an undetectable viral load during therapy. To qualify for treatment as a nonresponder at least 12 weeks must have elapsed since the first course of therapy.
Breakthrough	Patient's viral load was below the level of detection at one point during therapy but rose to >1000 copies per ml while on continuous therapy.
Relapse	Undetectable viral load increased to >1000 copies/ml after discontinuation of therapy
Sustained virological response (SVR)	HCV RNA negative 24 weeks after cessation of treatment

CHRONIC HEPATITIS B

Diagnosis of chronic hepatitis B virus infection

AND ONE of the following:

Two elevated ALT lab values within the past 12 months (> 60 IU/L for men, > 38 IU/L for women)and HBV DNA levels > 20,000 IU/ml
Patient has cirrhosis
Patient's liver biopsy showing moderate/severe necroinflammation (Grade 9-18) or significant fibrosis (Stage 3-4)

CHRONIC MYELOGENOUS LEUKEMIA (CML)

Diagnosis of chronic phase Philadelphia chromosome positive CML (Ph+ CML)

AND

Failure or clinically significant adverse effects to one of the following: Gleevec^R (imatinib), Tasigna^R (nilotinib) or Sprycel^R (dasatinib)

Coverage is Not Authorized For:

Uncontrolled autoimmune Hepatitis
A third course of therapy for patients who have failed to achieve sustained virological response following two courses of pegylated interferon and ribavirin
Patients less than 5 years of age
Monotherapy with pegylated interferon, unless ribavirin is contraindicated or the drug is requested for chronic hapatitis B
Patients with signs of liver decompensation [e.g., ascites, persistent jaundice, wasting, variceal hemorrhage, hepatic encephalopathy and preexisting cirrhosis] before or during treatment. These patients should be considered for liver transplantation. Consideration of therapy may be given to well compensated cirrhotics to avoid liver transplantation.
Use of Pegasys as prophylaxis following liver tansplant even with positive Hepatitis C donor
Following heart, lung or kidney transplants
Patients with previous history of drug or alcohol abuse who have not abstained for at least 3 months before starting therapy
To solely reduce the risk of developing hepatocellular carcinoma (HCC) in patients with cirrhosis
Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

Per NCCN Drugs and Biologics Compendium, pegylated interferons have a category 2A rating for treatment of chronic phase Philadelphia chromosome positive CML (Ph+ CML) if a patient is unable to tolerate treatment with Gleevec, Tasigna, Bosulif or Sprycel.
According to FDA approved labeling, recent evidence supports dose reduction of pegylated interferon for neutropenic hepatitis C patients treated with combination therapy (pegylated interferon and ribavirin). Treatment with Neupogen^R is not FDA approved or recommended according to current hepatitis C treatment guidelines.
Patients who develop anemia may be treated with epoetin to ensure that 80% of the original ribavirin dose is maintained throughout the course of therapy.
Genotype 6 is less responsive to treatment than genotypes 2 and 3. Treatment recommendations from Health Net expert reviewers are to treat genotype 6 in a similar manner to genotypes 1 and 4 with the exception of extending therapy to 72 weeks.
Patient co-infected with HIV should be evaluated by an HIV specialist to see if he/she needs to be treated with a HAART (highly active antiretroviral therapy) regimen that includes a component with activity against HBV (e.g. Viread^R-tenofovir, Epivir^R-lamivudine, or Emtriva^R-emtricitabine).
According to the American Gastroenterological Association (AGA), recommendations on the treatment of chronic hepatitis B (CHB) are as follows:
- HBV DNA results should be reported in IU/mL (1 IU/mL = 5.6 copies/mL)
- The upper limit of normal for serum ALT concentrations for men and women are 30 IU/L and 19 IU/L, respectively.
According to American Association for the Study of Liver Diseases (AASLD), recommendations on the treatment of CHB are as follows:
- Pegasys is the only pegylated interferon approved for the treatment of chronic hepatitis B in the United States. However, given the similarity in response rates between 90 and 180 mcg doses in the phase II trial, and the comparable response rates between 24 and 48 week treatment in the phase II and phase III trials, it is possible that lower doses and/or shorter duration of treatment may suffice for HBeAg-positive patients. Whether longer duration of treatment (>48 weeks) will result in higher rates of sustained response in HbeAg negative patients remains to be determined.
- Hepatitis B treatment is recommended if HBV DNA level or ALT becomes higher from baseline in HBeAg-negative CHB patients with initial HBV DNA levels of ≤ 2,000 IU/mL and normal ALT and
- Management of anti-viral resistant HBV should include monitoring of serum HBV DNA every 3-6 months during treatment. Prevention of resistance may be a greater benefit of combination therapy than enhanced potency; however, large well-designed studies are needed to confirm this concept. There are insufficient robust data to approve coverage of combination use.
- Grading and staging a liver biopsy for chronic hepatitis patients are as follows:
  - The grade is given a number based on the amount of inflammation (Knodell Scoring System).

0 = no inflammation
1-4 = minimal inflammation
5-8 = mild inflammation
9-12 = moderate inflammation
13-18 = marked inflammation

The stage is scored based on the amount of fibrosis or scarring (Metavir Scoring System).

0 = no scarring
1 = minimal scarring
2 = scarring has occurred and is outside the areas of the liver which include blood vessels
3 = bridging fibrosis
4 = cirrhosis or advanced scarring of the liver

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
PEG-Intron^R* (peginterferon alfa-2b) with ribavirin	Chronic Hepatitis C Peg-Intron 1.5 mcg/kg SQ/week Ribavirin dosing Genotype 1, 4, and 6: <65 kg: 800 mg PO/day ≥65 kg - 85 kg: 1000 mg PO/day >85 kg -105 kg: 1200 mg PO/day >105 kg: 1400 mg PO/day Genotype 2 or 3: 800 mg PO/day	1.5 mcg/kg/week
Peg-Intron^R* (peginterferon alfa-2b) monotherapy	Chronic Hepatitis C Any genotype where ribavirin is contraindicated: Peg-Intron 1.0 mcg/kg SQ/week	1.0 mcg/kg/week
Lamivudine (Epivir HBV)*	Chronic Hepatitis B 100 mg PO daily Dosage should be reduced in patients with renal impairment. Creatinine Clearance (mL/min): Dosing > 50: 100 mg QD 30-49: 100 mg first dose, then 50 mg QD 15-29: 100 mg first dose, then 25 mg QD 5-14: 35 mg first dose, then 15 mg QD <5: 35 mg first dose, then 10 mg QD	100 mg daily Dose in HIV co-infected patients will be 150 mg BID or 300 mg daily in combination with other antiretroviral therapy HBeAg(-) patients: The recommended treatment duration is longer than 1 year. The optimal duration of treatment for HBeAg negative patients has not been established. HBeAg(+) patients: Treatment should be continued until occurrence of persistent HBeAg seroconversion (HBeAg loss, anti-HBe detection, and undetectable serum HBV DNA) has been present for 6-12 months.
Adefovir dipivoxil (Hepsera)^*	Chronic Hepatitis B 10 mg PO daily Dosage should be reduced in patients with renal impairment. Creatinine Clearance (mL/min): Dosing > 50: 10 mg every 24 hrs 30-49: 10 mg every 48 hrs 10-29: 10 mg every 72 hrs Hemodialysis: 10 mg every 7 days following dialysis	10 mg daily HBeAg(-) patients: The recommended treatment duration is longer than 1 year. The optimal duration of treatment for HBeAg negative patients has not been established. HBeAg(+) patients: Treatment should be continued until occurrence of persistent HBeAg seroconversion (HBeAg loss, anti-HBe detection, and undetectable serum HBV DNA) has been present for 6-12 months.
Entecavir (Baraclude)^R *	Chronic Hepatitis B Epivir-HBV -naive patients: 0.5 mg PO daily Dosage should be reduced in patients with renal impairment Creatinine Clearance (mL/min): Dosing > 50: 0.5 mg once daily 30-49: 0.25 mg once daily or 0.5 mg every 48 hours 10-29: 0.15 mg once daily or 0.5 mg every 72 hours <10, hemodialysis, continuous ambulatory peritoneal dialysis (CAPD): 0.05 mg once daily or 0.5 mg every 7 days. If given on a hemodialysis day, administer following the hemodialysis session Patients with prior Epivir-HBV treatment or decompensated liver disease: 1 mg PO daily Dosage should be reduced in patients with renal impairment. Creatinine Clearance (mL/min): Dosing > 50: 1 mg once daily 30-49: 0.5 mg once daily or 1 mg every 48 hours 10-29: 0.3 mg once daily or 1 mg every 72 hours <10, hemodialysis, CAPD: 0.1 mg once daily or 1 mg every 7 days .	1 mg daily HBeAg(-) patients: The recommended treatment duration is longer than 1 year. The optimal duration of treatment for HBeAg negative patients has not been established. HBeAg(+) patients: Treatment should be continued until occurrence of persistent HBeAg seroconversion (HBeAg loss, anti-HBe detection, and undetectable serum HBV DNA) has been present for 6-12 months.
Telbivudine (Tyzeka)*	Chronic Hepetitis B 600 mg PO daily Dosage should be reduced in patients with renal impairment Creatinine Clearance (mL/min): Dosing > 50: 600 mg once daily 30-49: 600 mg every 48 hrs <30 (not on dialysis): 600 mg every 72 hrs ESRD: 600 mg every 96 hrs	600 mg daily HBeAg(-) patients: The recommended treatment duration is longer than 1 year. The optimal duration of treatment for HBeAg negative patients has not been established. HBeAg(+) patients: Treatment should be continued until occurrence of persistent HBeAg seroconversion (HBeAg loss, anti-HBe detection, and undetectable serum HBV DNA) has been present for 6-12 months.
Gleevec^R (imatinib)*	Philadelphia chromosome positive CML (Ph+ CML) 600 mg PO QD	800 mg/day
Sprycel^R (dasatinib)*	Philadelphia chromosome positive CML (Ph+ CML) 140 mg PO QD	180 mg/day
Tasigna^R (nilotinib)*	Philadelphia chromosome positive CML (Ph+ CML) 400 mg PO twice daily	800 mg/day
Bosulif^R (bosutinib)*	Philadelphia chromosome positive CML (Ph+ CML) 500 mg PO once daily with food	600 mg/day
Synribo^R (omacetaxine)*	Philadelphia chromosome positive CML (Ph+ CML) Induction Dose: 1.25 mg/m² SQ twice daily for 14 consecutive days of a 28-day cycle. Maintenance Dose: 1.25 mg/m² SQ twice daily for 7 consecutive days of a 28-day cycle.	2.5 mg/m²/day

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Pegasyswith ribavirin	Chronic Hepatitis C Adults: Pegasys 180 mcg (1 ml) SQ/week Pediatrics: Pegasys 180 mcg/1.73 m² x BSA SQ/week Ribavirin dosing Genotypes 1 and 4 Adults: < 75 kg: 1000 mg PO/day > 75 kg: 1200 mg PO/day Genotypes 2 and 3 Adults: 800 mg PO/day Pediatrics: 23-33 kg: 400 mg PO/day 34-46 kg: 600 mg PO/day 47-59 kg: 800 mg PO/day 60-74 kg: 1000 mg PO/day >75 kg: 1200 mg PO/day Combination therapy in adult patients with CHC and HIV Coinfection: Pegasys 180 mcg SQ/week AND ribavarin 800 mg PO/day	For combination therapy with a protease inhibitor (e.g., Incivek, Victrelis), approve pegylated interferon and ribavirin to coincide with the duration of the protease inhibitor authorization. Genotypes 1, 4, and 6 or any genotype and HIV co-infection: Initial authorization for 12 weeks If viral load undetectable at 12 weeks, authorize for an additional 36 weeks. If viral load remains detectable and there is at least a 2 log reduction at 12 weeks, authorize for an additional 12 weeks, and recheck viral load at 24 weeks. If viral load is detectable at 12 weeks and there was not a 2 log reduction, no additional authorization. If viral load is undetectable at 24 week recheck, authorize for an additional 24 weeks. For members with Genotype 1, 4 or 6 a detectable viral load and a 2 log₁₀ reduction at 12 weeks a total of 72 weeks can be authorized if viral load undetectable at 24 weeks. If viral load is detectable at 24 weeks, no additional authorization. Genotypes 2, 3: 24 weeks. No additional authorizations beyond 24 weeks Recurrence after liver transplant: 48 weeks Non-responders: Initial authorization for 12 weeks If viral load undetectable at 12 weeks, authorize for an additional 36 weeks (genotype 2 and 3) or 60 weeks (genotype 1, 4, 6). If viral load remains detectable and there is at least a 2 log₁₀ reduction at 12 weeks, authorize for an additional 12 weeks and recheck viral load. If viral load detectable at 12 weeks and there was not a 2 log₁₀ reduction, no additional authorization If viral load is undetectable at 24 week recheck, authorize for an additional 24 weeks (genotype 2, 3) or 48 weeks (genotype 1, 4, 6). If viral load is detectable at 24 weeks, no additional authorization. No more than one course of therapy as a non responder. Relapsers (all genotypes): Initial authorization 12 weeks If viral load undetectable at 12 weeks, an additional 36 weeks can be approved If viral load remains detectable and there is at least a 2 log reduction at 12 weeks, authorize for an additional 12 weeks, and recheck viral load at 24 weeks. If viral load is detectable at 12 weeks and there was not a 2 log reduction, no additional authorization. If viral load is undetectable at 24 week recheck, authorize for an additional 24 weeks. If viral load is detectable at 24 weeks, no additional authorization. No more than one course of therapy as a relapser
Pegasys monotherapy	Chronic Hepatitis C Pegasys 180 mcg (1 mL) SQ/week	Any Genotype where ribavirin is contraindicated: 48 weeks
Pegasys	Chronic Hepatitis B 180 mcg SQ/week as monotherapy	48 weeks
Pegasys	Philadelphia chromosome positive CML (Ph+ CML) 180 mcg (1 mL) SQ/week	Length of benefit For AHCS requests: One Year Treatment continues until no longer clinically beneficial or until unacceptable toxicity occurs

Product Availability:

Vials: 180 mcg/mL

Prefilled syringes: 180 mcg/0.5 mL (4 syringes/pack)

Autoinjector: 180 mcg/0.5 mL and 135 mcg/0.5 mL single use autoinjector

References:

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