Prior Auth Protocol

FDA Approved Indications:

Indicated for the treatment of chronic hepatitis C (CHC) genotype 1, 4, 5 or 6 infection in adults.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of hepatitis C virus (HCV) genotype 1, 4, 5 or 6 infection confirmed by detectable serum HCV RNA by quantitative assay. Baseline viral load by quantitative assay including genotype and treatment status of patient (treatment naive or treatment-experienced) are required.

AND

For genotype 1 and 4: Failure or clinically significant adverse effects to Zepatier (grazoprevir/elbasvir)

AND

For genotype 5 and 6: Failure or clinically significant adverse effects to Epclusa (sofosbuvir/velpatasvir)

AND

Patient is 18 years of age or older

AND

Any of the following clinical states identify candidates for treatment:
- Evidence of Stage 2 or greater hepatic fibrosis including one of the following: Liver biopsy confirming a METAVIR score F2 or greater OR Transient elastography (Fibroscan^R), score greater than or equal to 7.5 kPa; OR FibroSure (also known as FibroTest^R) score of greater than or equal to 0.48; OR APRI score greater than 0.7; OR FIB greater than 3.25.
- 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).
- Persons with hepatocellular carcinoma with life expectancy greater than 12 months
- 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)
- Men who have sex with men with high-risk sexual practices
- Active injection drug users
- Persons on long-term hemodialysis
- Women of childbearing age who wish to get pregnant
- HCV-infected health care workers who perform exposure-prone procedures

Criteria for Reauthorization/Continuation of Therapy:

Initial authorization criteria have been met, and
Evidence of lack of adherence may result in denial of treatment reauthorization.
Missed medical appointments related to the hepatitis C virus may result in denial of treatment authorization.

Coverage is Not Authorized For:

Dual therapy (Harvoni+(Sovaldi, or Olysio)
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 have failed treatment with either peginterferon alfa + ribavirin or an HCV protease inhibitor + peginterferon alfa + ribavirin.
Treatment-naive patients have no prior exposure to peginterferon alfa, ribavirin or an HCV protease inhibitor.
METAVIR Fibrosis Scores:
o F0 = No fibrosis
o F1 = Portal fibrosis without septa
o F2 = Portal fibrosis with few septa
o F3 = numerous septa without cirrhosis
o F4 = Cirrhosis
FibroSure (aka FibroTest) Scoring:
o <0.21 = Stage F0 = No fibrosis
o 0.21 - 0.26 = Stage F0 - F1
o 0.27 - 0.30 = Stage F1 = Portal fibrosis
o 0.31 - 0.47 = Stage F1 - F2
o 0.48 - 0.57 = Stage 2 = Bridging fibrosis with few septa
o 0.58 - 0.71 = Stage F3 = Bridging fibrosis with many septa
o 0.72 - 0.74 = Stage F3 - F4
o >0.74 = Stage F4 = Cirrhosis
Treatment with Harvoni for 8 weeks can be considered in treatment-naive patients without cirrhosis who have pre-treatment HCV RNA less than 6 million IU/mL. In the ION-3 trial, patients with a baseline HCV viral load of <6 million IU/mL and were treated with Harvoni for 8 weeks achieved SVR-12 at a rate of 97% versus 96% of those treated with Harvoni for 12 weeks.
Based on information presented as abstracts at the 2014 American Association for Study of Liver Disease (AASLD), this organization had made recommendation for the use of Harvoni outside of the approved indication. The AASLD treatment guideline include dosing recommendation for use in patients with decompensated cirrhosis, in patients with compensated cirrhosis who have relapsed following liver transplant and in patients who have failed previous treatment with a Sovaldi (sofosbuvir) based therapy.
There are currently neither published studies nor AASLD guidelines supporting the use of Harvoni in patients with hepatocellular carcinoma (HCC). Sovaldi (sofosbuvir) is currently approved by the FDA for patients with HCC.
Serious symptomatic bradycardia may occur in patients taking Harvoni with 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 Harvoni:
- 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.
Patients should be evaluated for readiness to initiate treatment. Patients selected for treatment shall be able and willing to strictly adhere to treatment protocols prescribed by their provider. Caution should be exercised with patients who have a history of treatment failure with prior hepatitis C treatment due to non-adherence with treatment regimen and appointments. Patients should be educated regarding potential risks and benefits of hepatitis C virus therapy, as well as the potential for resistance and failed therapy if medication is not taken as prescribed.
Evidence of lack of adherence may result in denial of treatment reauthorization.
Lost medications will not be replaced and may result in denial of treatment authorization. Replacement of stolen medications will require documentation and will be adjudicated on a case-by-case basis.
Missed medical and lab appointments may result in denial of treatment authorization.
Retreatment may be considered where there is evidence that such retreatment will improve patient outcomes according to AASLD guidelines.
HIV/HCV-coinfected persons should be treated and retreated the same as persons without HIV infection, after recognizing and managing interactions with antiretroviral medications.
Investigational services are not covered except when it is clearly documented that all of the following apply:
- Conventional therapy will not adequately treat the intended patient's condition;
- Conventional therapy will not prevent progressive disability or premature death;
- The provider of the proposed service has a record of safety and success with it equivalent or superior to that of other providers of the investigational service;
- The investigational service is the lowest cost item or service that meets the patient's medical needs and is less costly than all conventional alternatives;
- The service is not being performed as a part of a research study protocol;
- There is a reasonable expectation that the investigational service will significantly prolong the intended patient's life or will maintain or restore a range of physical and social function suited to activities of daily living; All investigational services require prior authorization. Payment will not be authorized for investigational services that do not meet the above criteria or for associated inpatient care when a beneficiary needs to be in the hospital primarily because she/he is receiving such non-approved investigational services.
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.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Zepatier	Genotype 1a: Treatment-naive or PegIFN/RBV experienced without baseline NS5A polymorphisms at amino acid positions 28, 30, 31, or 93 One tablet PO QD	12 weeks
Zepatier	Genotype 1b: Treatment-naive or PegIFN/RBV experienced One tablet PO QD	12 weeks
Zepatier	Genotype 4: Treatment-naive One tablet PO QD	12 weeks
Zepatier + ribavirin	Genotype 1a: Treatment-naive or PegIFN/RBV experienced with baseline NS5A polymorphisms at amino acid positions 28, 30, 31, or 93 One tablet PO QD plus BID ribavirin	16 weeks
Zepatier + ribavirin	Genotype 1a or 1b: PegIFN/RBV/PI-experienced One tablet PO QD plus BID ribavirin	12 weeks
Zepatier + ribavirin	Genotype 4: PegIFN/RBV-experienced One tablet PO QD plus BID ribavirin	16 weeks
Epclusa	Genotype 2 and 3: Without cirrhosis or with compensated cirrhosis, treatment naive or treatment experienced: One tablet PO QD	12 weeks
Epclusa + ribavirin	Genotype 2 and 3: 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
Harvoni	Genotype 1 CHC: 400 mg / 90 mg PO QD	Treatment naive patients without cirrhosis AND whose HCV viral load is less than 6 million IU/mL: 8 weeks or 12 weeks as requested May be filled in quantities up to 28 days at a time Treatment naive patients without cirrhosis AND whose HCV viral load is greater than or equal to 6 million IU/mL: 12 weeks May be filled in quantities up to 28 days at a time Treatment naive patients with compensated cirrhosis: 12 weeks May be filled in quantities up to 28 days at a time Treatment-experienced without cirrhosis: 12 weeks May be filled in quantities up to 28 days at a time Treatment-experienced with compensated cirrhosis: 24 weeks May be filled in quantities up to 28 days at a time Treatment-experienced with compensated cirrhosis in combination with ribavirin: 12 weeks May be filled in quantities up to 28 days at a time
Harvoni	Genotype 1 or 4 CHC with decompensated cirrhosis: 400 mg/90 mg QD plus ribavirin	12 weeks May be filled in quantities up to 28 days at a time
Harvoni	Treatment-naive and -experienced patients with Genotype 1 or 4 infection post liver transplantation, including compensated cirrhosis or decompensated cirrhosis: 400 mg/90 mg PO QD plus ribavirin	12 weeks May be filled in quantities up to 28 days at a time
Harvoni	Post liver transplant treatment-naive patients who are intolerant to RBV or RBV ineligible with HCV genotype 1 or 4 infection in the allograft, including compensated cirrhosis: 400 mg/90 mg QD	24 weeks May be filled in quantities up to 28 days at a time
Harvoni	Genotype 1 or 4 CHC with decompensated cirrhosis for patients in whom a prior sofosbuvir based therapy has failed: 400 mg/90 mg QD plus ribavirin	24 weeks May be filled in quantities up to 28 days at a time
Harvoni	Patients who have advanced fibrosis, in whom a previous sofosbuvir-containing regimen has failed: 400 mg/90 mg QD with or without ribavirin	24 weeks May be filled in quantities up to 28 days at a time
Harvoni	Treatment naive patients AND HIV co-infection without cirrhosis with Genotype 1, 4, 5 or 6 CHC: 400 mg / 90 mg PO QD	12 weeks May be filled in quantities up to 28 days at a time
Harvoni	Treatment-naive or treatment experienced patients with CHC genotype 4 infection with or without cirrhosis: 400 mg / 90 mg PO QD	12 weeks May be filled in quantities up to 28 days at a time
Harvoni	Treatment-naive or treatment experienced patients with CHC genotype 5 or genotype 6 infection with or without cirrhosis: 400 mg / 90 mg PO QD	12 weeks May be filled in quantities up to 28 days at a time

Product Availability:

Harvoni (sofosbuvir/ledipasvir) tablets: 400 mg/90 mg

References:

Harvoni [Prescribing Information]. Foster City, CA: Gilead Sciences, Inc.; November 2015.
Afdhal N, Zeuzem S, Kwo N et al. Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection. NEJM May 15, 2014 370;19: 1889-1898
Afdhal N, Reddy KR, Nelson DR et al. Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection. NEJM April 17,2014 370;16:1483-1493
Kowdley KV, Gordon SV, Reddy KR et al. Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis. NEJM May 15, 2014 370;19:1879-1888
American Association for the Study of Liver Disease Recommendations for Testing,Managing, and Treating Hepatitis C; October 2015. (accessed at: http://www.hcvguidelines.org)
European Association for Study of the Liver treatment guidelines April 2014 accessed at: http://files.easl.eu/easl-recommendations-on-treatment-of-hepatitis-C/index.html#p=4
WHO guidelines for treatment of hepatitis C April 2014 accessed at: http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1&ua=1