Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.28 Subject: Olysio Pegasys Ribavirin Page: 1 of 8 Last Review Date: December 18, 2017 Olysio Pegasys Ribavirin Description Pegasys (peginterferon alfa-2a) with Ribavirin (Copegus, Moderiba, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths) and Olysio (simeprevir) Background Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with the hepatitis C virus have no symptoms of the disease until liver damage becomes apparent, which may take several years. Most individuals then develop chronic hepatitis C (CHC). Some will also develop scarring and poor liver function (cirrhosis) over many years, which can lead to complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections or liver cancer. Olysio is a protease inhibitor that blocks a specific protein needed by the hepatitis C virus to replicate. It is to be used as a component of a combination antiviral treatment regimen. (1). Regulatory Status FDA-approved indications: Olysio is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of CHC in combination with peginterferon alfa and ribavirin in patients with HCV genotype 1 or 4 without cirrhosis or with compensated cirrhosis. Olysio must not be used as monotherapy (3).
Subject: Olysio Pegasys Ribavirin Page: 2 of 7 Pegasys, as part of a combination regimen, is an antiviral indicated for the treatment of CHC in patients with compensated liver disease. Pegasys in combination with ribavirin and an approved hepatitis C virus (HCV) NS3/4A protease inhibitor is indicated in adult patients (18 years of age and older) with HCV genotype 1 infection (2-5). Ribavirin is a nucleoside analogue indicated for the treatment of chronic hepatitis C (CHC) virus infection in combination with Pegasys in patients 5 years of age and older with compensated liver disease not previously treated with interferon alpha, and in adult CHC patients coinfected with HIV (2, 4-5). Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the NS3 Q80K polymorphism (3). Limitations of use: Olysio: (3) Efficacy of Olysio in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism. Olysio is not recommended in patients who have previously failed therapy with a treatment regimen that included Olysio or other HCV protease inhibitors. Pegasys: (2) Pegasys may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders. Ribavirin may cause birth defects and fetal death. Pregnancy should be avoided in female patients and female partners of male patients (2, 4-5). Additionally, Olysio has a boxed warning for Hepatitis B virus reactivation, occasionally fulminant, during or after Hepatitis C virus (HCV) therapy which have been reported in HBV/HCV coinfected patients who were not already on HBV suppressive therapy. In light of these observations, all patients initiating HCV therapy should be assessed for HBV coinfection with testing for HBsAg, anti-hbs, and anti-hbc (3). Rash has been observed during combination therapy with Olysio, peginterferon alfa and ribavirin. Discontinue Olysio if severe rash occurs (3).
Subject: Olysio Pegasys Ribavirin Page: 3 of 7 To prevent treatment failure, the dose of Olysio must not be reduced or interrupted. If treatment with Olysio is discontinued because of adverse reactions or inadequate on-treatment virologic response, Olysio treatment must not be reinstated (3). The safety and efficacy of Olysio in pediatric patients have not been established (3). The safety and efficacy of Olysio alone or in combination with peginterferon alfa and ribavirin have not been studied in liver transplant patients (3). Related policies Hepatitis C, PegIntron, Technivie Policy This policy statement applies to clinical review performed for pre-service (Prior Approval, Precertification, Advanced Benefit Determination, etc.) and/or post-service claims. Olysio in combination with Pegasys and ribavirin may be considered medically necessary in patients that are 18 years of age and older with chronic Hepatitis C if the conditions indicated below are met. Olysio in combination with Pegasys and ribavirin is considered investigational in patients less than 18 years of age and for all other indications. Prior-Approval Requirements Age 18 years of age or older Diagnosis Patient must have the following: Chronic Hepatitis C AND ALL of the following: 1. Viral genotype 1 or 4 and if subtype 1a does NOT have NS3 Q80k polymorphism 2. Detectable viral load in the serum
Subject: Olysio Pegasys Ribavirin Page: 4 of 7 3. A viral load will be drawn at treatment weeks 4, 12, and 24 4. Olysio will NOT be used as monotherapy 5. Olysio dose will NOT be reduced or interrupted 6. Compensated liver disease (i.e. stable liver problems; a diseased liver that is functional) 7. Patient has NOT been previously treated with a triple therapy regimen containing a hepatitis C virus protease inhibitor 8. Patient has NOT had a liver transplant 9. Neither the patient nor the partner of the patient is pregnant 10. If patient or their partner are of child bearing age, the patient has been or will be instructed to practice effective contraception during therapy and for 6 months after stopping ribavirin therapy 11. Must be prescribed by a board-certified gastroenterologist, hepatologist, oncologist, or infectious disease specialist 12. NO history of alcohol and/or substance abuse in the past 6 months 13. If the patient has a history of Hepatitis B (HBV) infection a. Prescriber agrees to monitor for HBV reactivation Prior Approval Renewal Requirements Age 18 years of age or older Diagnosis Patient must have ALL of the following: 1. Completed 12 weeks of Olysio 2. UNDETECTABLE hepatitis C viral load at treatment weeks 12 & 24 3. Patient had prior interferon-based therapy (dual therapy without a protease inhibitor) and relapsed or had a non-response (partial or null) Policy Guidelines Pre - PA Allowance None Prior - Approval Limits Duration
Subject: Olysio Pegasys Ribavirin Page: 5 of 7 Previously untreated patient (treatment naïve) or relapse HCV mono-infected patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) OR HCV/HIV-1 co-infected patients without cirrhosis 12 weeks for Olysio 24 weeks for Pegasys, and ribavirin Previously untreated patient (treatment naïve) or relapse HCV/HIV-1 co infected patients with compensated cirrhosis (Child-Pugh A) 12 weeks for Olysio 48 weeks for Pegasys, and ribavirin Previous non-responder (partial or null response) HCV/HIV-1 co-infected or HCV mono-infected patients without cirrhosis or with compensated cirrhosis 12 weeks for Olysio 48 weeks for Pegasys, and ribavirin Prior - Approval Renewal Limits Age 18 years of age or older Duration Previously untreated patient (treatment naïve) or a relapser NO additional authorization for Olysio, Pegasys, and ribavirin Previous non-responder (partial or null response) 20 weeks for Pegasys, and ribavirin
Subject: Olysio Pegasys Ribavirin Page: 6 of 7 Rationale Summary Olysio is to be used in combination with Pegasys and ribavirin in patients that are 18 years of age and older in the treatment of chronic Hepatitis C genotype 1 or 4 with compensated liver disease and no history of previous triple therapy. Olysio is not intended to be used as monotherapy. The safety and efficacy of Olysio alone or in combination with peginterferon alfa and ribavirin have not been studied in liver transplant patients. Ribavirin may cause birth defects and fetal death. Pregnancy should be avoided in female patients and female partners of male patients. Efficacy of Olysio in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the NS3 Q80K polymorphism (2-5). Prior authorization is required to ensure the safe, clinically appropriate and cost effective use of Pegasys, ribavirin, and Olysio while maintaining optimal therapeutic outcomes. References 1. Hepatitis. Medically reviewed by Judith Marcin, MD. May 9, 2017. http://www.healthline.com/health/hepatitis#types. Accessed on September 13 th, 2017. 2. Pegasys [package insert]. South San Francisco, CA: Genentech USA, Inc; March 2015. 3. Olysio [package insert]. Titusville, NJ: Janssen Therapeutics; May 2017. 4. Copegus [package insert]. South San Francisco, CA: Genentech USA, Inc; August 2015. 5. Rebetol capsules [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc; January 2016. 6. AASLD and IDSA: Recommendations for Testing, Managing, and Treating Hepatitis C; April 2017. www.hcvguidelines.org. Accessed on September 13 th, 2017. Policy History Date December 2013 March 2014 Action New addition to PA Annual review. Addition to criteria requirements that if the patient is Genotype 1 subtype 1a, the patient does NOT have NS3 Q80k polymorphism
Subject: Olysio Pegasys Ribavirin Page: 7 of 7 October 2014 Addition of specialist, and no alcohol or substance abuse in the last 6 months. Addition of Moderiba March 2015 Annual editorial review and reference update December 2015 Annual review Addition of genotype 4 March 2016 Annual editorial review and reference update Policy code changed from 5.03.28 to 5.01.28 December 2017 Annual editorial review and reference update Addition of HBV requirement Updated dosing based on package insert Keywords This policy was approved by the FEP Pharmacy and Medical Policy Committee on December 8, 2017 and is effective January 1, 2018.