Prior Auth Protocol

FDA Approved Indications:

For the treatment of chronic hepatitis C (CHC) genotype 1 or 4 infection as a component of a combination antiviral treatment regimen

Health Net Approved Indications and Usage Guidelines:

Diagnosis of CHC genotype 1 or 4 by detectable serum hepatitis C virus (HCV) RNA by quantitative assay.

AND

Prescribed by or in consultation with a gastroenterologist, hepatologist or infectious disease physician.

AND
Chart note documentation and copies of lab results are required

AND

For genotype 1, 4: A trial of Harvoni is required (Member must meet prior authorization criteria for and use Harvoni unless contraindicated)

AND

One of the following clinical states to identify candidates for treatment:
- Evidence of Stage 2 or greater hepatic fibrosis defined by one of the following:
  - Liver biopsy confirming a METAVIR score F2 or greater
  - Transient elastography (Fibroscan) score greater than or equal to 7.5 kPa
  - FibroSure (also known as FibroTest) score of greater than or equal to 0.48
  - APRI score greater than 0.7
  - FIB greater than 3.25
  - ARFI score of greater than 1.34 m/s
  - MRE score of greater than 3.20 kilopascals
  - HepaScore ≥0.55
  - FibroMeter ≥0.411
- Evidence of extra-hepatic manifestation of hepatitis C virus, such as type 2 or 3 essential mixed cryoglobulinemia with end- organ manifestations (e.g. vasculitis), or kidney disease (e.g. proteinuria, nephrotic syndrome or membranoproliferative glomerulonephritis).
- Pre- and post-liver transplant, or other solid organ transplant
- HIV-1 co-infection
- Hepatitis B co-infection
- Other coexistent liver disease (e.g. nonalcoholic steatohepatitis)
- Type 2 diabetes mellitus (insulin resistant)
- Porphyria cutanea tarda
- Debilitating fatigue impacting quality of life (e.g., secondary to extra-hepatic manifestations and/or liver disease) Fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest, and causes a substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months]
- Men who have sex with men with high-risk sexual practices
- Patients with a current injectable substance abuse disorder and actively participating in treatment
- Persons on long-term hemodialysis
- Women of childbearing age who wish to get pregnant
- HCV-infected health care workers who perform exposure-prone procedures

Coverage is Not Authorized For:

Monotherapy with Olysio (i.e., not in combination with peginterferon alfa and ribavirin)
Patients who have failed treatment with previous sofosbuvir based therapy
Acute hepatitis C or uncontrolled autoimmune hepatitis
Patients with decompensated liver disease (Child-Pugh score ≥ 9) before or during treatment. These patients should be considered for liver transplantation.
Failure with treatment regimen that includes Olysio or other HCV NS3/4A protease inhibitors (e.g., Victrelis (boceprevir)).
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:

Results from the phase II COSMOS study evaluated Olysio and Sovaldi in HCV patients including treatment naive or previous null responder HCV patients. In HCV patients with advanced liver fibrosis or cirrhosis (METAVIR F3 or F4) 90% of patients achieved SVR-12. In treatment experienced patients with METAVIR scores of F0-F2, 94% of patients achieved SVR-12. In patients with Q80K polymorphism, 51 of 58 (88%) achieved SVR-12 when treated with Olysio and Sovaldi for 12 or 24 weeks. Patients with the HCV Q80K polymorphism had inferior outcomes using Olysio plus, peginterferon and ribavirin with no significant difference in SVR12 rates observed when comparing the Olysio group (SVR 58%) to the placebo group (SVR 55%) for treatment naive patients. Prior relapse patients also showed no significant difference between the Olysio group (SVR 47%) and placebo group (SVR 30%)
Olysio contains a sulfonamide moiety but patients in clinical trials allergic to sulfa did not experience any increased incidence of rash. However, there is insufficient data to rule out an association between sulfa allergy and severity of adverse reaction.
Efficacy has not been established for patients who have previously failed therapy with a treatment regimen that includes Olysio or other HCV NS3/4A protease inhibitors (e.g. boceprevir, telaprevir).
Safety and efficacy has not been established in patients with: solid organ transplant; HCV and human immunodeficiency virus co-infection; HCV patients with hepatitis B virus co-infection; and hepatic impairment defined by a Child-Pugh score ≥7 (class B and C) or decompensated liver disease.
METAVIR Fibrosis Scores:
- F0 = No fibrosis
- F1 = Portal fibrosis without septa
- F2 = Portal fibrosis with few septa
- F3 = numerous septa without cirrhosis
- F4 = Cirrhosis
FibroSure (aka FibroTest) Scoring:
- <0.21 = Stage F0 = No fibrosis
- 0.21 - 0.26 = Stage F0 - F1
- 0.27 - 0.30 = Stage F1 = Portal fibrosis
- 0.31 - 0.47 = Stage F1 - F2
- 0.48 - 0.57 = Stage 2 = Bridging fibrosis with few septa
- 0.58 - 0.72 = Stage F3 = Bridging fibrosis with many septa
- 0.73 - 0.74 = Stage F3 - F4
- >0.74 = Stage F4 = Cirrhosis
Health Net, Inc. considers serum marker testing (FibroSure), transient elastography, also known as ultrasound based elastography or FibroScan, acoustic radiation force impulse (ARFI) imaging, and magnetic resonance elastography (MRE) for detecting or monitoring hepatic fibrosis in persons with hepatitis C as valid alternative tests to liver biopsy, to be consistent with UpToDate's recommendation that liver biopsy is not routinely done and decision to treat can be made on history, physical exam, laboratory tests, and noninvasive assessment of liver fibrosis.
- Per manufacturer, FibroSure score of greater than or equal to 0.49 corresponds to a Metavir score of greater than or equal to 2.
- In the largest-scaled meta-analysis that included 50 studies, mean AUROC curves for the diagnosis of significant fibrosis (Metavir score of greater than or equal to 2) was 0.84 (with 1 corresponding to a perfect test), with optimal FibroScan cutoff value of 7.65 kilopascals.
- A pooled meta-analysis of 518 patients (total of 8 studies) with chronic liver diseases including CHC, the AUROC was 0.87 for the diagnosis of significant fibrosis (Metavir score of greater than or equal to 2) with optimal ARFI cutoff value of 1.34 m/s with sensitivity of 79% and specificity of 85%. Furthermore, a large multicenter study of 914 patients with CHC reported the optimal ARFI cutoff value to be greater than 1.33 m/s for diagnosis of Metavir score of greater than or equal to 2 with AUROC of 0.79.
- A study of 114 patients with CHC reported the optimal cutoff MRE value for differentiating F0-F1 fibrosis from F2-F4 fibrosis was 3.20 kilopascals with sensitivity of 88.5% and specificity of 100%. In multiple studies on patients of liver fibrosis from varied etiologies (including CHC), sensitivity and specificity values of MRE in differentiating F0-F1 from ≥F2 fibrosis were 85% to 100% and 86% to 100%, respectively and cutoff values ranged from 2.5 to 4.9 kilopascals, with majority above 3 kilopascals.
The FIBROSpect II is a commercially available test that combines hyaluronic acid, tissue inhibitor of a metalloproteinase-1 (TIMP-1), and alpha-2-macroglobulin in a predictive algorithm for fibrosis stages (F2 to F4). An index score of greater than 0.42 is classified with the presence of stage F2 to F4 fibrosis, but is unable to differentiate amongst each of the fibrosis stages F2, F3 and F4.
Serious symptomatic bradycardia may occur in patients taking Olysio in combination with sofosbuvir (Sovaldi) and amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered Olysio and Sovaldi:
- Counsel patients about the risk of serious symptomatic bradycardia
- Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.
Child-Pugh Score

	1 Point	2 Points	3 Points
Bilirubin	Less than 2 mg/dL Less than 34 5mol/L	2-3 mg/dL 34-50 5mol/L	Over 3 mg/dL Over 50 5mol/L
Albumin	Over 3.5 g/dL Over 35 g/L	2.8-3.5 g/dL 28-35 g/L	Less than 2.8 g/dL Less than 28 g/L
INR	Less than 1.7	1.7 - 2.2	Over 2.2
Ascites	None	Mild / medically controlled	Moderate-severe / poorly controlled
Encephalopathy	None	Mild / medically controlled Grade I-II	Moderate-severe / poorly controlled. Grade III-IV

Diagnostic criteria for chronic fatigue syndrome was developed by an expert committee convened by the Institute of Medicine on the basis of a comprehensive literature review and input from patient, advocacy, and research communities. These diagnostic criteria state that symptoms should persist for at least 6 months and be present at least half the time with moderate, substantial, or severe intensity to distinguish chronic fatigue syndrome from other diseases.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Harvoni* (sofosbuvir/ledipasvir)	One tablet PO QD for 12 weeks	24 weeks
Epclusa*	Without cirrhosis or with compensated cirrhosis, treatment naive or treatment experienced: One tablet PO QD	12 weeks
Epclusa plus ribavirin*	With decompensated cirrhosis (Child-Pugh class B or C) treatment naive or treatment experienced: One tablet PO QD plus weight based ribavirin	12 weeks

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Olysio* plus Sovaldi* * Requires prior authorization	Treatment-naive patients with HCV genotype 1a infection without cirrhosis: Sovaldi 400 mg PO QD plus Olysio150 mg PO QD with or without weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg])	12 weeks
Olysio* with Sovaldi* * Requires prior authorization	Treatment-naive patients with HCV genotype 1a infection with cirrhosis: Sovaldi 400 mg PO QD plus Olysio150 mg PO QD with or without weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg])	24 weeks
Olysio* with Sovaldi* * Requires prior authorization	Treatment-naive patients with HCV genotype 1b infection and without cirrhosis: Sovaldi 400 mg plus Olysio 150 mg PO QD	12 weeks
Olysio* with Sovaldi* * Requires prior authorization	Treatment-naive patients with HCV genotype 1b infection and with cirrhosis: Sovaldi 400 mg plus Olysio 150 mg PO	24 weeks
Olysio* * Requires prior authorization	Treatment-naive, prior relapsers, and prior non-responders to Peg-IFN/RBV treatment with HCV genotype 4 infection: Olysio150 mg PO QD with weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]) and PEG-IFN	12 weeks

Product Availability:

150 mg capsules

References:

1. Olysio, [Prescribing Information]. Titusville, NJ: Janssen, LP; October 2015.

2. Ghany MG, Strader DB, Thomas DL, Leonard SB. Diagnosis, Management, and Treatment of Hepatitis C: An Update. American Association for the Study of Liver Diseases. Hepatology. 2009. Volume 49, Number 9: 1335-1374.

3. American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) Recommendations for Testing, Managing, and Treating Hepatitis C. June 2015: http://www.hcvguidelines.org/full-report-view

4. Chopra, S, Arora, S. Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on July 29, 2014.)

5. Practice of FibroTest for hepatitis C. BioPredictive website. Available at: http://www.biopredictive.com/intl/physician/fibrotest-for-hcv/. Accessed July 23, 2014.

6. Friedrich-rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134(4):960-74.

7. Friedrich-rust M, Nierhoff J, Lupsor M, et al. Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis. J Viral Hepat. 2012;19(2):e212-9.

8. Sporea I, Bota S, Peck-radosavljevic M, et al. Acoustic Radiation Force Impulse elastography for fibrosis evaluation in patients with chronic hepatitis C: an international multicenter study. Eur J Radiol. 2012;81(12):4112-8.

9. Ichikawa S, Motosugi U, Ichikawa T, et al. Magnetic resonance elastography for staging liver fibrosis in chronic hepatitis C. Magn Reson Med Sci. 2012;11(4):291-7.

10. Venkatesh SK, Yin M, Ehman RL. Magnetic resonance elastography of liver: clinical applications. J Comput Assist Tomogr. 2013;37(6):887-96.

11. Lawitz E, Sulkowski MS, Ghalib R et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. The Lancet Published online July 28, 2014 http://dx.doi.org/10.1016/S0140-6736(14)61036-9.

12. Institute of Medicine of the National Academies. Beyond Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome Redefining an Illness. Report Brief, February 2015. Available at https://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf, accessed October 7, 2015.