Month Date, Year Health Plan Addressee Line 1 Health Plan Addressee Line 2 Dear (Insert Name), I am requesting

(approval/reconsideration of your denial) of Olysio (simeprevir) plus Sovaldi (sofosbuvir) for my patient (patient name). (Patient name) has chronic hepatitis C (HCV) genotype 1 infection with stage (3 or 4) fibrosis (or compensated cirrhosis). (He/she) is unable to take an interferon-alfa (and/or ribavirin) containing regimen due to the following contraindication(s): (one or more of: prior intolerance to interferon or ribavirin (describe), contraindication such as psychiatric disease, autoimmune disease, cardiopulmonary disease, concern about relapse with injections, anemia that cannot be corrected with iron supplementation) Olysio+Sovaldi has shown efficacy for HCV genotype 1 patients that are treatment nave or previous null responders (patients who had less than a 2-log decline in HCV RNA levels by 12 weeks of treatment with pegylated interferon and ribavirin), including patients with cirrhosis. In a phase 2a study by Jacobson et al, known as COSMOS, patients from two cohorts were randomized to one of four treatment groups.1 Cohort 1 consisted of 80 null responders with mild to moderate liver fibrosis (METAVIR F0-2). Cohort 2 consisted of 87 patients, either treatment nave or null responders, with advanced fibrosis or compensated cirrhosis (METAVIR F3-4). Analysis was done on each cohort separately. Treatment arm 1 patients received Olysio+Sovaldi+ribavirin (RBV) for 24 weeks. Treatment arm 2 received Olysio+Sovaldi for 24 weeks. Treatment arm 3 received Olysio+Sovaldi+RBV for 12 weeks, and treatment arm 4 received Olysio+Sovaldi for 12 weeks. Table 1 displays interim sustained virological response (SVR) results for the 12 week treatment arms.
Table 1: Interim SVR results for cohort 1 and cohort 2 patients in the 12-week treatment arms of the COSMOS study1 Cohort Treatment arm 3 Treatment arm 4 Olysio+Sovaldi +RBV x12w Cohort 1:SVR12 (Null/F0-2) Cohort 2: SVR4 (Nave or Null/F3-4) 26/27 (96.3%) 14/14 (100%) 26/27 (96%) 13/14 (93%) Olysio+Sovaldi x12w

Approved options for HCV genotype 1 contain interferon, with the exception of Sovaldi+RBV for 24 weeks in interferon-intolerant patients, as shown in Table 2.
Table 2: Results from phase 3 studies of Olysio or Sovaldi in genotype 1, treatment nave patients Study Treatment regimen SVR12 name Quest-12 Neutrino3 Olysio+peg-interferon+RBV RGT x2448w Sovaldi+peg-interferon+RBV x12w Sovaldi+peg-interferon+RBV x 12 w (patients with cirrhosis) SPARE4 Sovaldi+RBV x 24 w 80%

90% 80%

68%

Olysio for 12 weeks+peg-interferon+RBV for 48 weeks was studied in 17 prior null responders in a phase 2 study (ASPIRE) and 9/17 (53%) achieved SVR5. There are no clinical data for Sovaldi+peg-interferon+RBV or Sovaldi+RBV in treatment experienced patients, including prior null responders. Sovaldi+RBV for 24 weeks has lower SVR rates than were seen in COSMOS and the cost of that regimen is expected to be over $176,000. Recent data on the real world cost of treatment of HCV with peg-interferon+RBV plus telaprevir found that patients with advanced fibrosis (FIB-4>3.25) cost $256,977 per SVR6. These high costs were driven by low SVR rates in these difficult to treat patients as well as costs of managing adverse events, especially anemia. In summary, Olysio+Sovaldi is the only available treatment combination that is an interferonfree regimen with demonstrated efficacy in genotype 1 HCV. I am requesting that Olysio+Sovaldi be approved for my patient, (insert patient name) based on (his/her) advanced liver disease and contraindications to an interferon-based regimen. Sincerely,

(Name) (Affiliation)

Jacobson IM, Ghalib,RM, Rodriguez-Torres M, et al. SVR results of a once-daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naive and prior null responder patients: the COSMOS study (Abstract LB-3). Presented at 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2013. November 1-5. Washington, DC.
2

Jacobson IM, Dore GJ, Foster GR, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-nave patients: results from QUEST-1 a phase III trial (Abstract 1425). Presented at 48th Annual Meeting of the European Association for the Study of the Liver (EASL); 2013.April 24-28. Amsterdam, the Netherlands.
3

Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T et al. Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection. (NEUTRINO/FISSION). The New England Journal of Medicine. 2013; 368 (20). 1878-1887.
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Osinusi A, Meissner EG, Lee YJ, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013 Aug 28;310(8):80411. doi: 10.1001/jama.2013.109309.
5

Fried MW, Poordad F, Zeuzem S, et al. Safety and tolerability of TMC435 in combination with peginterferon -2a and ribavirin for treatment of HCV genotype 1 infection in treatment-naive and experienced patients (PILLAR and ASPIRE trials) (Abstract 769). Presented at 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) 2012; November 9-13. Boston, MA. Bichoupan K, Martel-Laferriere V, Ng M, SchonfeldE et al. Real world costs of telaprevir-based triple therapy, including costs of managing adverse events, at the Mount Sinai Medical Center, NY: $195,000 per SVR12 (Abstract 244). Presented at 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2013. November 1-5. Washington, DC.
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