Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Daklinza Sovaldi Page: 1 of 7 Last Review Date: June 24, 2016 Daklinza Sovaldi Description Daklinza (daclatasvir) and Sovaldi (sofosbuvir) 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 hepatitis C virus (HCV) have no symptoms of the disease until liver damage becomes apparent, which may take several years. Some people with chronic HCV infection 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). Daclatasvir in combination with sofosbuvir is the first all oral 12-week regimen specifically for the treatment of hepatitis C genotype 3. Clinical trial tested a 12-week, ribavirin-free regimen and resulted in sustained virologic response (SVR12) in 98% of treatment-naïve and 92% of treatment-experienced genotype 3 with non-cirrhotic patients. Approximately 10% of HCV patients in the U.S. have genotype 3 (1). Regulatory Status FDA-approved indications: Daklinza is a hepatitis C virus (HCV) NS5A inhibitor indicated for use with sofosbuvir, with or without ribavirin, for the treatment of chronic HCV genotype 1 or 3 infection (2).
Subject: Daklinza Sovaldi Page: 2 of 7 Sovaldi is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of genotype 1, 2, 3, 4 chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen (3). Limitations of Use: Daklinza Sustained virologic response (SVR12) rates are reduced in genotype 3 patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks (2). Off-Label Uses: Daclatasvir with sofosbuvir for 12 weeks was approved by the FDA for the treatment of HCV genotype 3 infection in patients without and with cirrhosis. Although daclatasvir with sofosbuvir was not approved for the treatment of HCV genotype 2 infection, daclatasvir maintains adequate activity against HCV genotype 2 despite a 50% effective concentration (EC 50) that increases by several logs in the presence of the prevalent M31 polymorphism (4). Daklinza is contraindicated in combination with drugs that strongly induce CYP3A and may lead to lower exposure and loss of efficacy. Daklinza dose should be increased to 90mg once a day (2). Safety and effectiveness of Daklinza and Sovaldi in pediatric patients younger than 18 years of age have not been established (2, 3). Related policies Harvoni, Olysio, Sovaldi, Viekira Pak, Technivie, 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. Daklinza used in combination with Sovaldi may be considered medically necessary in patients 18 years of age or older with chronic Hepatitis C (required documented viral load (HCV RNA) at least 6 months prior to request for treatment) in patients with genotype 1 that have had inadequate response, intolerance, or contraindication to Harvoni therapy; in patients with genotype 2 that have had inadequate response, intolerance, or contraindication to Sovaldi and ribavirin therapy; in patients with genotype 3 that have inadequate response, intolerance, or contraindication to prior therapy with Sovaldi and ribavirin; in patients with genotype 4 with decompensated cirrhosis that have had inadequate response, intolerance, or contraindication to
Subject: Daklinza Sovaldi Page: 3 of 7 Harvoni therapy; used in combination with Sovaldi; absence of severe renal impairment (egfr less than 30 ml/min/1.73m 2 ) or end stage renal disease (ESRD) requiring hemodialysis; with no history of alcohol and/or substance abuse in the past 6 months; when combined with ribavirin then absence of significant or unstable cardiac disease, neither the patient nor the partner of the patient is pregnant, and 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. Daklinza used in combination with Sovaldi is considered investigational for patients that are under 18 years of age and for all other indications. Prior-Approval Requirements Age 18 years of age or older Diagnoses Patient must have the following: Chronic Hepatitis C (Required documented viral load (HCV RNA) at least 6 months prior to request for treatment.) AND ONE of the following: 1. Genotype 1: a. Inadequate response, intolerance, or contraindication to Harvoni therapy 2. Genotype 2: a. Inadequate response to prior therapy with Sovaldi and ribavirin 3. Genotype 3: a. Inadequate response to prior therapy with Sovaldi and ribavirin 4. Genotype 4 with decompensated cirrhosis a. Inadequate response to prior therapy with Harvoni therapy AND ALL of the following:
Subject: Daklinza Sovaldi Page: 4 of 7 1. Used in combination with Sovaldi 2. Absence of severe renal impairment (egfr less than 30 ml/min/1.73m 2 ) or end stage renal disease (ESRD) requiring hemodialysis 3. NO history of alcohol and/or substance abuse in the past 6 months AND ALL of the following if combined with ribavirin (RBV) therapy: 1. Absence of significant or unstable cardiac disease 2. Neither the patient nor the partner of the patient is pregnant 3. 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 Prior Approval Renewal Requirements None Policy Guidelines Pre - PA Allowance None Prior - Approval Limits Duration Genotype / Experienced No Compensated Decompensated 1 2 Peg-INF and Ribavirin NS3 Protease Inh. & Peg-INF & Ribavirin Peg-INF and Ribavirin with or without Ribavirin Intolerant:
Subject: Daklinza Sovaldi Page: 5 of 7 Sovaldi Genotype / Experienced 2 3 Peg-INF and Ribavirin Sovaldi Peg-INF and Ribavirin Sovaldi with or without with or without No with or without Compensated with or without 4 N/A N/A Decompensated Ribavirin Intolerant: 1, 2, 3, 4 Post Transplant: & Experienced Ribavirin Ribavirin Intolerant: Intolerant: (84 tablets per 84 days) (168 tablets per 168 days) (84 tablets per 84 days) (168 tablets per 168 days) N/A Rationale
Subject: Daklinza Sovaldi Page: 6 of 7 Summary Daclatasvir in combination with sofosbuvir; is the first all oral 12-week regimen specifically for the treatment of hepatitis C genotype 3. Clinical trial tested a 12-week, ribavirin-free regimen and resulted in sustained virologic response (SVR12) in 98% of treatment-naïve and 92% of treatment-experienced genotype 3 with non-cirrhotic patients. Daklinza in combination with sofosbuvir with or without ribavirin can be used in the treatment of hepatitis C genotype1 and 2. Safety and effectiveness of Daklinza and Sovaldi in pediatric patients younger than 18 years of age have not been established (1-4). Prior authorization is required to ensure the safe, clinically appropriate and cost effective use of Daklinza when taken in combination with Sovaldi while maintaining optimal therapeutic outcomes. References 1. FDA News Release. FDA approves new treatment for chronic hepatitis C genotype 3 infections. July 24, 2015. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm455888.htm 2. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; February 2016 3. Sovaldi [package insert]. Foster City, CA: Gilead Sciences, Inc; August 2015. 4. AASLD and IDSA: Recommendations for Testing, Managing, and Treating Hepatitis C; April 2016. www.hcvguidelines.org Policy History Date August 2015 September 2015 December 2015 March 2016 Action New addition to PA Annual Review Annual review and reference update Addition of genotypes 1 and 3 with additional requirements to policy of inadequate response, intolerance, or contraindication to Harvoni for genotype 1 and Sovaldi and ribavirin with genotype 2; and quantity limits for both. Annual review Addition of genotype 4 with decompensated cirrhosis Removal of the requirement of no decompensated liver disease and not had a liver transplant -or- is treatment naïve post-transplant Policy change from 5.03.36
Subject: Daklinza Sovaldi Page: 7 of 7 June 2016 Keywords Annual editorial review and reference update Addition of the duration table Removal of must be prescribed by a board-certified gastroenterologist, hepatologist, oncologist, or infectious disease specialist Addition of Daklinza 90mg This policy was approved by the FEP Pharmacy and Medical Policy Committee on June 24, 2016 and is effective on July 1, 2016. Deborah M. Smith, MD, MPH