Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.27 Subject: Olysio PegIntron Ribavirin Page: 1 of 7 Last Review Date: March 18, 2016 Olysio PegIntron Ribavirin Description PegIntron (peginterferon alfa-2b) 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 of these people then go on to develop chronic hepatitis C. 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 (1). 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. In clinical studies, Olysio was evaluated in combination with peginterferon-alfa and ribavirin, two drugs also used to treat hepatitis C virus infection. Olysio is intended for adults with compensated liver disease (a diseased liver that is still functioning), including cirrhosis, who have not received treatment for their infection (treatment naïve) or for whom previous treatment has not been effective (treatment experienced) (1). It is unlikely that patients with inadequate on-treatment virologic response will achieve a sustained virologic response (SVR), therefore discontinuation of treatment is recommended in
Subject: Olysio PegIntron Ribavirin Page: 2 of 7 these patients. The HCV RNA thresholds that trigger discontinuation of treatment is an undetectable HCV RNA (viral load) in Week 4, 12, and 24 (3). In all patients, treatment with Olysio should be initiated in combination with peginterferon alfa and ribavirin and should be administered for 12 weeks (3). All treatment-naïve and prior relapser patients, including those with cirrhosis, should receive an additional 12 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with Olysio, peginterferon alfa and ribavirin (total treatment duration of 24 weeks) (3). All prior non-responder patients (including partial and null-responders), including those with cirrhosis, should receive an additional 36 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with Olysio, peginterferon alfa and ribavirin (total treatment duration of 48 weeks) (3). Regulatory Status FDA-approved indications: PegIntron, as part of a combination regimen, is an antiviral indicated for the treatment of chronic hepatitis C (CHC) in patients with compensated liver disease (2). PegIntron 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). Ribavirin is a nucleoside analogue indicated for the treatment of chronic hepatitis C (CHC) virus infection in combination with PegIntron 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). Olysio is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) genotype 1 or 4 infection as a component of a combination antiviral treatment regimen (3). Limitations of use: PegIntron: (2) PegIntron 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. Olysio: (3)
Subject: Olysio PegIntron Ribavirin Page: 3 of 7 1. Olysio monotherapy is not recommended 2. Olysio combination with peginterferon alfa and ribavirin: screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism is strongly recommended and alternative therapy should be considered if HCV genotype 1a with Q80K is detected 3. Olysio is not recommended in patients with moderate or severe hepatic impairment (Child Pugh Class B or C) 4. Olysio is not recommended in patients who have previously failed therapy with a treatment regimen that included OLYSIO or other HCV protease inhibitors Ribavirin may cause birth defects and fetal death. Pregnancy should be avoided in female patients and female partners of male patients (2-4). Rash has been observed during combination therapy with Olysio, peginterferon alfa and ribavirin. Discontinue Olysio if severe rash occurs (3). 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 children and adolescents less than 18 years of age has not been established. 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 Daklinza, Harvoni, Pegasys, Sovaldi, Technivie, Viekira Pak, Zepatier 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 PegIntron and ribavirin may be considered medically necessary in patients that are 18 years of age or older with chronic Hepatitis C viral genotype 1 or 4 (without a NS3 Q80k polymorphism if subtype 1a); with a detectable viral load in the serum; viral loads will be drawn at treatment weeks 4, 12 and 24; not used as monotherapy and dose will not be reduced or interrupted; patient has compensated liver disease (i.e. stable lever problems, a diseased liver that is functional); no previous treatment with a triple therapy regimen containing a hepatitis C virus protease inhibitor; no history of a liver transplant; neither the patient nor the
Subject: Olysio PegIntron Ribavirin Page: 4 of 7 partner of the patient is pregnant and will be instructed on the practice of effective contraception while on medication therapy and for 6 months after stopping the ribavirin regimen; must be prescribed by a board-certified gastroenterologist, hepatologist, oncologist, or infectious disease specialist; and no history of alcohol and/or substance abuse in the past 6 months. Olysio in combination with PegIntron 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, the patient does NOT have NS3 Q80k polymorphism 2. Detectable viral load in the serum 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
Subject: Olysio PegIntron Ribavirin Page: 5 of 7 Prior Approval Renewal Requirements 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 Previously untreated patient (treatment naïve) or relapser 12 weeks for Olysio 24 weeks for PegIntron, and ribavirin Previous non-responder (partial or null response) 12 weeks for Olysio 28 weeks for PegIntron, and ribavirin Prior - Approval Renewal Limits Duration Previously untreated patient (treatment naïve) or a relapser NO additional authorization for Olysio, PegIntron, and ribavirin Previous non-responder (partial or null response) 20 weeks for PegIntron, and ribavirin
Subject: Olysio PegIntron Ribavirin Page: 6 of 7 Rationale Summary Olysio is to be used in combination with PegIntron 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. It is unlikely that patients with inadequate on-treatment virologic response will achieve a sustained virologic response (SVR), therefore discontinuation of treatment is recommended in these patients. The HCV RNA thresholds that trigger discontinuation of treatment is an undetectable HCV RNA (viral load) in Week 4, 12, and 24. 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. 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). Prior authorization is required to ensure the safe, clinically appropriate and cost effective use of PegIntron, ribavirin, and Olysio while maintaining optimal therapeutic outcomes. References 1. FDA Newspress Announcement. FDA Approves New Treatment for Hepatitis C Virus. November 22, 2013. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm376449.htm 2. PegIntron [package insert]. Kenilworth, NJ: Schering, a subsidiary of Merck & Co., Inc; September 2015. 3. Olysio [package insert]. Titusville, NJ: Janssen Therapeutics; October 2015. 4. Rebetol capsules [package insert]. Whitehouse Station, NJ: Merck & CO. Inc; May 2015. 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 PegIntron 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 Policy code changed from 5.03.27 to 5.01.27 Keywords This policy was approved by the FEP Pharmacy and Medical Policy Committee on March 18, 2016 and is effective April 1, 2016. Deborah M. Smith, MD, MPH