Prior Auth Protocol

FDA Approved Indications:

Indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. Sovaldi efficacy has been established in subjects with hepatitis C virus (HCV) genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplant) and those with HCV/HIV-1 co-infection.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of CHC confirmed by detectable serum HCV RNA by quantitative assay. Genotype is required to determine length of approval.

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, 5, 6: A trial of Harvoni is required (Member must meet prior authorization criteria for and use Harvoni unless contraindicated)

OR

For genotype 2, 3: A trial of Epclusa (sofosbuvir/velpatasvir) is required (Member must meet prior authorization criteria for and use Epclusa 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).
For treatment of CHC in patients with hepatocellular carcinoma with a life expectancy greater than 12 months meeting Milan criteria (awaiting liver transplantation): Milan criteria is defined as 1 lesion ≤5 cm, up to 3 lesions each of which are ≤3 cm, and no extrahepatic manifestations/no vascular invasion
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 for the disorder
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:

Treatment of HCV as monotherapy
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:

Treatment experienced patients include those who were intolerant to treatment, relapsed following treatment or were partial or null responders to treatment.
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
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.
APRI and FibroSpect II have the lowest specificity values compared to FibroSure, FibroScan, ARFI and MRE
The combination of Sovaldi plus pegylated interferon and ribavirin has been evaluated in patients with genotype 3 infection. In 2 phase 2 clinical trials, PROTON and ELECTRON, 38 of 39 (97%) treatment-naive patients with genotype 3 infection achieved SVR with sofosbuvir plus PEG (4 to 12 weeks of therapy)/RBV. The AASLD guidelines suggest daily Sovaldi (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) plus weekly pegylated interferon alfa for 12 weeks is an acceptable regimen for interferon-eligible persons with HCV genotype 3.
Gane et al. studied 10 patients treated with Sovaldi monotherapy for 12 weeks who had genotype 2 or 3 disease. The primary efficacy (sustained virologic response (SVR) at 12 weeks after therapy stopped) was much lower (60%) on monotherapy versus 100% on combination therapy.
The triple therapy (Sovaldi+peginterferon+ribavirin) combination study included patients with genotype 1, 4, 5 or 6 disease (NEUTRINO study).
There are no efficacy and safety data in the published literature to support using the combination of Sovaldi and Olysio for the treatment of genotype 6 HCV infection. Sovaldi plus peginterferon alfa-2a and ribavirin was studied in a small sample of patients (n=6) and further data are needed to prove efficacy and safety.
The POSITRON trial defines contraindications to interferon as those patients with psychiatric disorders (57% of patients in the trial) and autoimmune disorders (19% of patients in the trial). Unacceptable side effects with interferon were influenza-like symptoms (32% of patients), psychiatric disorders (20% of patients), thrombocytopenia (16% of patients) or local or systemic adverse reactions (12% of patients). Per AASLD Practice guideline (2009), additional characteristics of persons for whom therapy with interferon/ribavirin may be contraindicated include untreated thyroid disease, pregnancy, severe concurrent medical conditions (uncontrolled diabetes, uncontrolled hypertension, significant coronary heart disease) or solid organ transplant (renal, heart, lung).
There are no data to support combination quadruple therapy with peginterferon, ribavirin, Sovaldi and a protease inhibitor (Olysio).
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.
- A HepaScore ≥0.55 is considered "positive" and indicates a METAVIR score of F2 to F4.
Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with Sovaldi in combination with an investigational agent (the NS5A inhibitor daclatasvir) or simeprevir. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered 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.
The dosing for unlabeled uses of Sovaldi are from the current American Association for the Study of Liver Diseases treatment guidelines.
Child-Pugh Score

	1 Point	2 Points	3 Points
Bilirubin	Less than 2 mg/dL Less than 34 umol/L	2-3 mg/dL 34-50 umol/L	Over 3 mg/dL Over 50 umol/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

Child-Pugh class is determined by the total number of points: A = 5-6 points; B = 7-9 points; C = 10-15 points

There is no dosing recommendation for patients with severe renal impairment (estimated glomerular filtration rate < 30mL/minute/1.73m² or with end stage renal disease due to higher exposures (up to 20 fold) of the predominant sofosbuvir metabolite.
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
Sovaldi, Olysio (simeprevir)	Genotype 1, treatment naive or treatment experienced with pegylated interferon (PEG-IFN) and ribavirin (RBV) without cirrhosis; Sovaldi 400 mg plus Olysio 150 mg PO QD with or without weight-based RBV	12 weeks
Sovaldi, Olysio	Genotype 1, treatment naive or treatment experienced with PEG-IFN and RBV with compensated cirrhosis; Sovaldi 400 mg plus Olysio 150 mg PO QD with or without weight-based RBV	24 weeks
Sovaldi, Olysio	Liver transplant patients with genotype 1 in allograft with or without compensated cirrhosis; Sovaldi 400 mg plus Olysio 150 mg PO QD with or without weight-based RBV	12 weeks
Sovaldi, Daklinza	Genotype 1, treatment naive or treatment experienced with Peg-IFN/RBV with or without protease inhibitor, and without cirrhosis: Sovaldi 400 mg plus Daklinza 60 mg PO QD	12 weeks
Sovaldi, Daklinza	Genotype 1, treatment naive or treatment experienced with Peg-IFN/RBV with or without protease inhibitor, and with cirrhosis: Sovaldi 400 mg plus Daklinza 60 mg PO QD with or without weight based RBV	24 weeks
Sovaldi, Daklinza	Genotype 1 or 4 with decompensated cirrhosis (including those with hepatocellular carcinoma): Sovaldi 400 mg plus Daklinza 60 mg PO QD with RBV	12 weeks
Sovaldi, Daklinza	Genotype 1 or 4 with decompensated cirrhosis (including those with hepatocellular carcinoma) and intolerant of RBV: Sovaldi 400 mg plus Daklinza 60 mg PO QD	24 weeks
Sovaldi, Daklinza	Genotype 1, 2, 3 or 4 infection in the allograft, including those with compensated cirrhosis: Sovaldi 400 mg plus Daklinza 60 mg PO QD with RBV	12 weeks
Sovaldi, Daklinza	Genotype 1, 2, 3 or 4 infection in the allograft, including those with compensated cirrhosis and intolerant of RBV: Sovaldi 400 mg plus Daklinza 60 mg PO QD	24 weeks
Sovaldi, Daklinza	Genotype 2, treatment naive without cirrhosis, AND, unable to tolerate RBV: Sovaldi 400 mg plus Daklinza 60 mg PO QD	12 weeks
Sovaldi, Daklinza	Genotype 2 who are not eligible to receive IFN, in whom previous treatment with Sovaldi/RBV has failed: Sovaldi 400 mg plus Daklinza 60 mg PO QD with or without weight based RBV	24 weeks
Sovaldi, Daklinza	Genotype 3, treatment naive or treatment experienced with Peg IFN/RBV without cirrhosis; Sovaldi 400 mg plus Daklinza 60 mg PO QD	12 weeks
Sovaldi, Daklinza	Genotype 3, treatment naive or treatment experienced with Peg IFN/RBV with cirrhosis; Sovaldi 400 mg plus Daklinza 60 mg PO QD	24 weeks
Sovaldi, Daklinza	Genotype 3 who are not eligible to receive IFN, in whom previous treatment with Sovaldi/RBV has failed: Sovaldi 400 mg plus Daklinza 60 mg PO QD with weight based RBV	24 weeks
Sovaldi, RBV	Genotype 2, treatment naive without cirrhosis; Sovaldi 400 mg weight-based RBV	12 weeks
Sovaldi, RBV	Genotype 2, treatment naive with cirrhosis; Sovaldi 400 mg plus weight-based RBV	16 weeks
Sovaldi, RBV	Liver transplant patient with genotype 2 in the allograft, includingcompensated cirrhosis; Sovaldi 400 mg plus weight-based RBV	24 weeks
Sovaldi, RBV	Genotype 3, treatment naive; Sovaldi 400 mg plus weight-based RBV	24 weeks
Sovaldi, RBV	Genotype 2 or 3 with decompensated cirrhosis (moderate or severe hepatic impairment; CTP class B or C) who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma); Sovaldi 400 mg plus weight-based RBV	Up to 48 weeks
Sovaldi, RBV	Liver transplant patient with genotype 3 in the allograft, including compensated cirrhosis; Sovaldi 400 mg plus weight-based RBV	24 weeks
Sovaldi, RBV	Liver transplant patient with genotype 3 treatment-naive and -experienced liver transplant recipients with infection in the allograft with decompensated cirrhosis (Child Turcotte Pugh class B or C); Sovaldi 400 mg plus weight-based RBV	24 weeks
Sovaldi, RBV	Genotype 4, treatment naive without cirrhosis; Sovaldi 400 mg plus weight-based RBV	24 weeks
Sovaldi, RBV	Hepatocellular carcinoma patients awaiting liver transplantation: Sovaldi 400 mg PO QD (in combination with ribavirin)	48 weeks or until liver transplantation, whichever occurs first
Sovaldi, RBV, PEG-IFN	Genotype 2 or 3 infection, who are eligible to receive IFN, and treatment experienced with Peg IFN/RBV or with Sovaldi/ RBV: Sovaldi 400 mg and weight-based RBV plus weekly PEG-IFN	12 weeks
Sovaldi, RBV, PEG-IFN	Genotype 4, treatment naive Sovaldi 400 mg and weight-based RBV plus weekly PEG-IFN	12 weeks
Sovaldi, RBV, PEG-IFN	Genotype 5, treatment naive Sovaldi 400 mg and weight-based RBV plus weekly PEG-IFN	12 weeks
Sovaldi, RBV, PEG-IFN	Genotype 6, treatment naive Sovaldi 400 mg and weight-based RBV plus weekly PEG-IFN treatment-naive patients	12 weeks
Sovaldi, RBV	Genotype 2, treatment experienced with PegIFN/RBV: Sovaldi 400 mg plus weight-based RBV	16 weeks to 24 weeks
Sovaldi, RBV	Genotype 2, treatment experienced with PegIFN/RBV: Sovaldi 400 mg plus weight-based RBV	16 weeks to 24 weeks

Product Availability:

Sovaldi tablets: 400 mg

References:

1. Sovaldi [Prescribing Information]. Foster City, CA: Gilead Sciences, Inc.; August 2015.

2. Harvoni [Prescribing Information]. Foster City, CA: Gilead Sciences, Inc.; June 2016.

3. Gane E, Stedman C, Hyland R et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;36:34-44.

4. Jacobson I, Gordon S, Kowdley K et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;268:186-77.

5. Lawitz E, Mangia A, Wyles D et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878-1887.Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693-9

6. American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) Recommendations for Testing, Managing, and Treating Hepatitis C. February 2016: http://www.hcvguidelines.org/full-report-view

7. Pegasys [Prescribing Information]. South San Francisco, CA: Genentech USA, Inc.; July 2013.

8. Rebetol [Prescribing Information]. Whitehouse Station, NJ: Merck and Co., Inc.; November 2013.

9. 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.)

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

11. 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.

12. 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.

13. 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.

14. 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.

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

16. Kalantari H, Hoseini H. Babak A, et al. Validation of Hepascore as a Predictor of Liver Fibrosis in Patients with Chronic Hepatitis C Infection. Hepat Res Treat. 2011:972759. doi: 10.1155/2011/972759. Epub 2011 Dec 28.

17. 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.

18. 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.

19. Bonder A, Afdhal N.Utilization of FibroScan in clinical practice. Curr Gastroenterol Rep. 2014 Feb;16(2):372. doi: 10.1007/s11894-014-0372-6.

20. 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.