Prior Auth Protocol

FDA Approved Indications:

Peg-Intron

Treatment of Chronic Hepatitis C (CHC) in patients with compensated liver disease
- In combination with REBETOL (ribavirin) and an approved Hepatitis C Virus (HCV) NS3/4A protease inhibitor in adult patients (18 years of age and older) with HCV genotype 1 infection
- In combination with REBETOL in patients with genotypes other than 1, pediatric patients (3-17 years of age), or in patients with genotype 1 infection where use of an HCV NS3/4A protease inhibitor is not warranted based on tolerability, contraindications or other clinical factors
- Monotherapy (for patients who are intolerant to ribavirin): CHC in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.

Sylatron

Adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy.

Health Net Approved Indications and Usage Guidelines:

Chronic Hepatitis C

For all patients

Patient is 3 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

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 genotype 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

Patient has symptomatic cryoglobulinemia

OR

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

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 increased to > 1000 copies/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 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 (imatinib), Tasigna (nilotinib) or Sprycel (dasatinib)

Melanoma:

Diagnosis of Stage III melanoma with microscopic lymph node involvement within 84 days of surgical resection.

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
Monotherapy with pegylated interferon, unless ribavirin is contraindicated
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 PEG-Intron as prophylaxis following liver transplant 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 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 inteferon 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.
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
Pegasys^R(peginterferon alfa-2a) with ribavirin*	Chronic Hepatitis C Pegasys 180 mcg SC/ week Reduce dose by 50% if profound neutropenia develops Ribavirin dosing Genotypes 1 and 4: < 75 kg: 1000 mg PO/day >75 kg: 1200 mg PO/day Genotypes 2 and 3: 800 mg PO/day	180 mcg/week
Pegasys^R (peginterferon alfa-2a) monotherapy*	Chronic Hepatitis C: Any genotype where ribavirin is contraindicated: Pegasys 180 mcg SC/week	180 mcg/week
Gleevec^R (imatinib)*	Ph+ CML chronic phase: 600 mg PO QD	800 mg/day
Sprycel^R (dasatinib)*	Ph+ CML chronic phase: 140 mg PO QD	180 mg/day
Tasigna^R (nilotinib)*	Ph+ CML chronic phase: 400 mg PO twice daily	800 mg/day
Bosulif^R (bosutinib)*	Ph+ CML chronic phase: 500 mg PO once daily with food	600 mg/day
Synribo^R (omacetaxine)*	Ph+ CML chronic phase: Induction Dose: 1.25 mg/m² administered by subcutaneous injection twice daily for 14 consecutive days of a 28-day cycle. Maintenance Dose: 1.25 mg/m² administered by subcutaneous injection twice daily for 7 consecutive days of a 28-day cycle.	2.5 mg/m²/day
Sovaldi^R (sofosbuvir)	Chronic Hepatitis C Genotype 1 or 4: 400 mg PO QD Genotype 2 and 3 400 mg PO QD (in combination with ribavirin)	400 mg daily
Intron A^R (interferon alfa-2b)	Melanoma Induction: 20 million units/m² IV for 5 consecutive days per week for 4 weeks Maintenance: 10 million units/m² SC 3 times weekly for 48 weeks	20 million units/m²daily

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
PEG-Intron	Chronic Hepatitis C: Peg-Intron 1.5 mcg/kg SC/week Reduce dose by 50% if profound neutropenia develops Ribavirin dosing (Genotypes 1 and 4): <65 kg: 800 mg PO/day 66 kg - 80 kg: 1000 mg PO/day >81 kg -105 kg: 1200 mg PO/day >105 kg: 1400 mg PO/day Ribavirin dosing (Genotypes 2 and 3): 800 mg PO/day Pediatric patients: Peg-Intron 60 mcg/m²/week SC Ribavirin dosing: <47 kg: 15 mg/kg/day PO 47 kg - 59 kg: 800 mg/day PO 60 kg - 73 kg: 1000 mg/day PO >73 kg: 1200 mg/day PO	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 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. For members with genotype 1 or 4 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. This does not apply to genotype 6. If viral load is detectable at 24 weeks, no additional authorization. Genotypes 2 and 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 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 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. If viral load is detectable at 24 weeks, no additional authorization No more than one course of therapy as a relapser
PEG-Intron	Chronic Hepatitis C: Peg-Intron 1.0 mcg/kg SQ/week	Any genotype where ribavirin is contraindicated: One year
PEG-Intron	Philadelphia chromosome positive CML (Ph+ CML): 1.5 mcg/kg SQ/week	NATL: Length of benefit AHCS: One Year Treatment continues until no longer clinically beneficial or until unacceptable toxicity occurs
Sylatron	Melanoma: 6 mcg/kg/week SC for 8 doses, followed by 3 mcg/kg/week SC for up to 5 years	NATL: 5 years AHCS: One year

Product Availability:

Peg-Intron

Vials (with diluent): 50 mcg/0.5 mL, 80 mcg/0.5 mL, 120 mcg/0.5 mL and 150 mcg/0.5 mL

Redipen: 50 mcg/0.5 mL, 80 mcg/0.5 mL, 120 mcg/0.5 mL, and 150 mcg/0.5 mL

Sylatron

Single-use vials: 296 mcg lyophilized powder, 444 mcg lyophilized powder, or 888 mcg lyophilized powder

References:

PEGIntron [Prescribing information], Whitehouse Station, NJ: Schering Corporation. May 2015.
Rebetol [Prescribing information], Whitehouse Station, NJ: Merck Sharp & Dohme Corporation. May, 2015.
Manns MP, McHutchison JG, Gordon SC, et al. For the Hepatitis Interventional Therapy Group. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A Randomized Trial. Lancet. 2001;358:958-965.
National Institutes of Health Consensus Development Conference Statement: Management of Hepatitis C: 2002. Final Statement. August 26, 2002.
Hadziyannis S, et al. Peginterferon alfa-2a (40KD) (Pegasys) in combination with ribavirin (RBV): Efficacy and safety results from a phase III, randomized, double-blind, multicenter study examining effect of duration of treatment and RBV dose. EASL. 2002.
Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, Management, and Treatment of Hepatitis C: An Update. Hepatology. 2009;49 (4):1335-1374. Available at: www.aasld.org. Accessed June 9, 2015.
Pegasys[ Prescribing information]. South San Francisco, CA: Genentech USA, Inc., March 2015.
Copegus [ Prescribing information].South San Francisco, CA: Hoffmann-La Roche Pharmaceuticals. February 2013.
Keeffe EB. Chronic Hepatitis C: management of treatment failures. Clin Gastroenterol Hepatol. 2005;3(10 Suppl 2):S102-S105.
Sethi A, Shiffman M. Approach to the management of patients with chronic hepatitis C who failed to achieve sustained virologic response. Clin Liver Dis. 2005;9(3):453-471.
Fontana RJ. Optimizing outcomes in hepatitis C: is treatment beyond 48 weeks ever justified? Gastroenterol. 2006;130(4):1357-1361.
Hoefs JC, Morgan TR. Seventy-two weeks of peginterferon and ribavirin for patients with partial early virologic response? Hepatology. 2007,46(6):1671-1674.
Pearlman BL, Ehleben C, Saifee S. Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis C genotype 1-infected slow responders. Hepatology. 2007;46(6):1688-1694.
DrugDex Drug Database. Thompson Micromedex Web site. Available at: http://www.micromedex solutions.com. Accessed June 9, 2015.
McEvoy GK, ed. AHFS:Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:761-775.
FDA Drug Info Web site. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed June 9, 2015.
AHFS Drug Information Updates Web site. Available at: http://www.ahfsdruginformation.com. Accessed June 9, 2015.
National Comprehensive Cancer Network. Chronic Myelogenous Leukemia Version 1. 2015. Available at http://www.nccn.org. Accessed June 8, 2015.
Sylatron [prescribing information]. Whitehouse Station, NJ: Schering Corporation; May 2015.
National Cancer Institute. National Institute of Health. Available at www.cancer.gov. Accessed July 01, 2015
Clinical Pharmacology accessed at http://www.clinicalpharmacology-ip.com/ Accessed July 01, 2015

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 increased to > 1000 copies/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