Hepatitis C Treatment in Oregon

Transcription

1 The Hepatitis C Advisory Group, 12/21/2014 Hepatitis C Treatment in Oregon Introduction The rising health care burden of HCV infection in Oregon is occurring at this time of growing interest in containing medical care costs nationally and limiting Oregon Medicaid expenditures demanded by the OHP waiver. Recently available HCV treatment regimens promise cure rates of greater than 95% with a 2 to 3 month course of oral medication resulting in a 70% to 90% reduction in complications and death from advanced liver disease. This holds the promise of congruent savings in the costs of HCV related liver disease. Increasing numbers of HCV infected Oregonians are presenting for treatment for several reasons: 1) increasing numbers of symptomatic patients with advanced liver disease in the infected cohort; 2) increased screening of the 1945 to 1965 birth cohort; 3) expansion of Medicaid in the context of the Affordable Care Act; and, 4) the warehousing of patients with prior treatment failure, medication intolerance, treatment contraindications or preference for eminent more effective, less toxic medications who are now eligible for treatment. In the context of excessive pricing of new HCV medications, effective treatment of the infected population requires creative approaches by public and private payers to expand funding available for HCV patient treatment and aggressively seek lower drug costs. It is estimated that there are > 95,000 persons infected with hepatitis C in Oregon, with nearly ¼ represented by the state Medicaid population. Well under ½ of these persons are aware of their HCV infection. With increasing enrollment, in the last 6 months, the estimates of the number of diagnosed HCV patients within the Oregon Health Plan population has risen 5,800 to 10,900. It is estimated that 35% of this population has advanced fibrosis (Stage 3 4, F3 F4) and is at highest risk for complications of cirrhosis, liver caner and death. There are approximately 400 deaths per year in Oregon attributed of complications of HCV related cirrhosis and about another 100 due to HCV related liver cancer. There are approximately 800 hospitalizations in Oregon per year due to HCV related disease with an average stay of 5 days (~$27,000 per hospitalization). This represents as cost of~ $21 million per year, and rising, with ~62% for the costs billed to Medicare and Medicaid. The age adjusted death rate from HCV in Oregon is ~10/100,00, over twice the national average and >4X the HIV mortality rate, which it surpassed in In recent years, 79% of HCV deaths have occurred in persons aged years. HCV mortality rates in Oregon are 2 fold higher among Native Americans and blacks compared to whites.

2 Estimated HCV Costs in Oregon: impact of new treatments To assist in state Medicaid policy development, Dan Hartung, PharmD, MPH, in concert with members of the HCV advisory board, developed a series of economic models to project the future impact of currently available all oral HCV treatment regimens on Medicaid costs and health benefits. Using Markov transition state models, 30 year costs and health benefits for cohort of 50 year old patients with chronic hepatitis C treated with sofosbuvirbased regimens (depending on genotype SOF/LED for GT 1 and SOF/R for G2 and G3) were simulated compared to no treatment and previous standards of care. Transition state probabilities, drug efficacy, and costs of hepatitis C related care were derived from the literature. Drug costs were estimated using Medicaid average acquisition costs (AAC) net CMS mandated and supplemental rebates. We conducted sensitivity analyses to determine the time horizon, subgroups of liver disease, and drug rebates at which downstream reductions in HCV related care translate into cost savings for the state Medicaid program. An economic projection for treating the anticipated number of individuals with Metavir F3/F4 liver disease using Medicaid claims data was then developed. In the anticipated genotype one (G1) population, sofosbuvir/ledipasvir (SOF/LED) treatment would average $100,147 in HCV related health care costs per patient and yield life years. Treatment of boceprevir based therapy (BOC), dual therapy (PR), or no treatment (NTx) would cost $34,190, $27,845, and $35,711 respectively, and result in 20.78, 19.72, and additional life years. Incremental costs per life year gained (not quality adjusted) for SOF/LED are $22,645 relative to BOC, $17,343 relative to PR and $11,090 compared to no treatment. At no time point or net drug cost with rebate over 50% off AAC does SOF/LED become economically preferred to BOC, PR, or no treatment. Among a population with advanced fibrosis bridging fibrosis or cirrhosis (40%/60%), incremental costs per life year gained for SOF/LED are $10,194 compared to BOC and $5,830 compared to PR. We project 10,898 OHP enrollees with CHC, 3,000 of which we estimate having Metavir F4/F3. By way of comparison, good values for medical treatment based on cost/benefit analysis are considered to be less than $100,000 to $120,000 per quality adjusted life year (QALY) gained, such as combination antiretroviral therapy for HIV/AIDS ($10,000 to $20,000 per QALY) or dialysis for end stage kidney failure ($50,000 to $100,000 per QALY). Using SOF based regimens, we estimate the total cost of treating CHC infected individuals in the Oregon Medicaid population to be $910 million over 30 years. Treating the highest priority patients (F4/F3) over a six year period would costs roughly $50 million per year for the first six years. Treatment with all oral HCV regimens is highly cost effective by most standards. Because their high upfront costs are not recouped through reductions in downstream CHC complications, financing remains a challenge for state Medicaid programs.

3 When and in Whom to Initiate HCV Therapy HCV Treatment is Most Likely to Provide the Most Immediate and Impactful Benefits? Based on the AASLD/IDSA Guidelines: Highest Priority for Treatment Owing to Highest Risk for Severe Complications Advanced fibrosis (Metavir F3) or compensated cirrhosis (Metavir F4) Rating: Class I, Level A Organ transplant Rating: Class I, Level B Type 2 or 3 essential mixed cryoglobulinemia with end organ manifestations (e.g., vasculitis) Rating: Class I, Level B Proteinuria, nephrotic syndrome, or membranoproliferative glomerulonephritis Rating: Class IIa, Level B Assessment of fibrosis can be based on liver biopsy, Fibroscan, and serum assays such as FibroSpect, Fibrosure, FIB 4, and APRI. Cirrhotic patients do not require further fibrosis assessment if there is clinical (ascites, encephalopathy, varices), laboratory (elevated total bilirubin, low albumin, elevated INR, and/or thrombocytopenia), and/or radiologic evidence of cirrhosis. Patient s readiness for treatment should be based on provider and medical records data. If there is abuse history of drugs and alcohol, abstinence should be for 6 months. If alcohol is occasionally consumed with no evidence of abuse, hepatitis C treatment should not be delayed. Treatment Recommendations Since overall treatment costs are high, it is reasonable to consider the least expensive treatment options where there is equivalent or little data available. This should not only lower the overall treatment costs for treating the hepatitis C population, but allow potentially more patients to be treated in the long run. With this in mind, for many of the subpopulations such as treatment experienced cirrhotics, the sample sizes in the majority of studies (even in the large registration trials) are small. At the AASLD 2014 meetings additional studies of equivalent or larger sample sizes evaluating specific subpopulations of hepatitis C patients were presented. Many of these studies demonstrated that shorter

4 duration of treatment gave in many instances similar SVR rates (treatment duration 12 weeks versus 24 weeks). The Recommendations below highlight emerging data that allows the use of 12 weeks or less treatment duration to markedly reduce cost and at the same time maintain similar SVR rates in the hepatitis C population. Of note, the HCV/HIV coinfected data suggests that efficacy and safety are similar to regimens used for HCV monoinfected patients. Therefore, the following treatment recommendations apply to both populations.

5 Genotype 1 HCV Patients Naïve Patients Treatment naive non-cirrhotic genotype 1 with HCV RNA< 6 million IU/mL Treatment naive genotype 1 with HCV RNA> 6 million IU/mL Harvoni 1 tablet QD 1 Harvoni 1 tablet QD 1 8 wks Treatment naive non-cirrhotic genotype 1b 2 Treatment naive non-cirrhotic genotype 1a + Ribavirin 2 Treatment naive genotype 1 with cirrhosis Harvoni 1 tablet QD + Ribavirin 2,3 **For decompensated cirrhotics start with Ribavirin dose of 600mg QD 1. Havroni package insert 2. Ferenci, et al NEJM 2014; 370: Viekira package insert.

6 Genotype 1 HCV Patients Treatment Experienced Patients Treatment experienced genotype 1 without cirrhosis Harvoni 1 tablet QD + Ribavirin 1 Treatment experienced genotype 1 with cirrhosis Harvoni 1 tablet QD plus Ribavirin mg** 2 Treatment experienced genotype 1b and 1a relapsers, partial responders with cirrhosis Treatment experienced genotype 1a null responder with cirrhosis + Ribavirin 3,4 + Ribavirin 3,4 24 wks **For decompensated cirrhotics start with Ribavirin dose of 600mg QD 1. Zeuzem, et al NEJM 2014; 370: Abstract # 82 and LB #4 (previous PI failures), AASLD Poordad et al NEJM 2014; 370: and Fried Liver Meeting 2014, Abst #81 4. Viekira Package Insert

7 5. Genotype 2 HCV Treatment Naive Patients Population Treatment naive and previous relapsers Recommended Regimen Sofosbuvir 400 mg + RBV mg/day Duration Genotype 2 HCV Treatment Experienced Patients Nonresponse to previous treatment with pegifn/rbv Sofosbuvir 400 mg + RBV mg/day * *Patients with cirrhosis may benefit by extension of therapy to 16 wks (89% vs 82%).

8 Genotype 3 HCV Treatment Naive Patients Regardless of IFN eligibility Harvoni + Ribavirin mg/day 1 Overall 100% SVR (n=26) (16% were cirrhotic) (Emerging regimen) Sofosbuvir 400 mg + RBV mg/day Non-cirrhotic 93% SVR (n=92) Cirrhotic 92% SVR (n=13) (FDA-approved) 24 wks 1. Gane, EASL 2014 Genotype 3 HCV Treatment Experienced Patients Regardless of IFN eligibility Harvoni + Ribavirin mg/day Non-cirrhotic 89% SVR (n=28) Cirrhotic 73% SVR (n=22) 2 (Emerging regimen) Sofosbuvir 400 mg + RBV mg/day Non-cirrhotic 85% SVR (n=100) Cirrhotic 60% SVR (n=45) (FDA-approved) 24 wks 2. Gane, Liver Meeting 2014, LB Abst #11 (Electon II)

9 Genotype 4 and 6 HCV Patients Genotype 4 Harvoni 1 tablet QD 1 Overall 95% SVR (n=20) (Emerging regimen) Genotype 6 Harvoni 1 tablet QD 2 Overall 96% SVR (n=25) (Emerging regimen) 1. Ruane, EASL Gane Liver Meeting 2014 Abst LB 11