SECTION 1: OLYSIO with (PEGASYS) AND RIBAVIRIN SECTION 2: OLYSIO with (PEGINTRON) AND RIBAVIRIN RATIONALE FOR INCLUSION IN PA PROGRAM SECTION 1: OLYSIO with (PEGASYS) AND RIBAVIRIN 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). 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). 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). 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. SECTION 2: OLYSIO with (PEGINTRON) AND RIBAVIRIN
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) (2). Because patients with an inadequate on-treatment virologic response (i.e., HCV RNA greater or equal to 25IU/mL) are not likely to achieve a sustained virologic response (SVR), discontinuation of treatment is recommended in these patients. The HCV RNA threshold that trigger discontinuation of treatment is a viral load of 25IU/mL or greater during treatment weeks 4, 12 and 24 (2). Regulatory Status FDA-approved indications: Olysio is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) in combination with peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) in patients with HCV genotype 1 or 4 infection with cirrhosis or with compensated cirrhosis (2). 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. 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 (2-4). 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 (3,4). Limitations of use: Olysio: (2) Efficacy of Olysio in combination with Peg-IFN-alfa and RBV 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 PegIntron: (3) 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. Ribavirin may cause birth defects and fetal death. Pregnancy should be avoided in female patients and female partners of male patients (4). Rash has been observed during combination therapy with Olysio, peginterferon alfa and ribavirin. Discontinue Olysio if severe rash occurs (2). 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 (2). The safety and efficacy of Olysio pediatric patients have 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 (2). 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 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 (2). 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. Hepatitis. Medically reviewed by Judith Marcin, MD. May 9, 2017. Accessed on 9/7/2017 http://www.healthline.com/health/hepatitis#types 2. Olysio [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP; May 2017. 3. PegIntron [package insert]. Whitehouse, NJ: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc; February 2016. 4. Rebetol capsules [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.; Inc; January 2016.