- Email: [email protected]
P0798 : The cost-effectiveness of sofosbuvir- and simeprevirbased therapies for HCV genotype 1 infection
POSTERS P0798 THE COST-EFFECTIVENESS OF SOFOSBUVIR- AND SIMEPREVIRBASED THERAPIES FOR HCV GENOTYPE 1 INFECTION B.P. Linas1 , J.R. Morgan2 , M.T. Pho3 , J.A. Leff4 , B.R. Schackman4 , S.A. Assoumou1 , J.A. Salomon5 , K.A. Freedberg6 , A.Y. Kim7 . 1 School of Medicine, 2 School of Public Health, Boston University, Boston, 3 School of Medicine, University of Chicago, Chicago, 4 Weill Cornell School of Medicine, Cornell University, New York, 5 School of Public Health, Harvard University, 6 Medical Practice Evaluation Center, 7 Department of Medicine, Massachusetts General Hospital, Boston, United States E-mail: [email protected] Background and Aims: New regimens to treat HCV genotype 1 are highly effective, but costly. We estimated quality-adjusted life expectancy (QALE), costs, and incremental cost-effectiveness ratios (ICERs) for strategies to treating HCV genotype 1 treatment-naïve and treatment-experienced patients with and without cirrhosis. Table: Cost-effectiveness of treatment regimens for HCV genotype 1 in treatment naïve and experienced patients with and without cirrhosis Strategy
Cost
QALY
Naïve No Cirrhosis, RNA <6 Million (8 weeks SOF/LDV) No treatment 161,000 8.5 PEG/RBV 48 weeks 202,000 11.0 PEG/RBV/SMV 24 weeks 227,000 13.8 SOF/LDV 8 weeks 229,000 14.3 PEG/RBV/SOF 12 weeks 260,000 14.1 Naïve No Cirrhosis, RNA ≥6 Million (12 weeks SOF/LDV) No treatment 161,000 8.5 PEG/RBV 48 weeks 202,000 11.1 PEG/RBV/SMV 24 weeks 227,000 13.8 SOF/LDV 12 weeks 257,000 14.3 PEG/RBV/SOF 12 weeks 260,000 14.1 Naïve Cirrhosis (12 weeks SOF/LDV) No treatment 96,000 4.8 PEG/RBV 48 weeks 156,000 7.0 PEG/RBV/SMV 24 weeks 201,000 10.9 PEG/RBV/SOF 12 weeks 248,000 12.3 SOF/LDV 12 weeks 252,000 13.9 Experienced No Cirrhosis (12 weeks SOF/LDV) No treatment 160,000 8.5 SOF/LDV 12 weeks 259,000 14.3 PEG/RBV/SOF 12 weeks 261,000 14.1 SOF/SMV 12 weeks 324,000 14.1 Experienced Cirrhosis (24 weeks SOF/LDV) No treatment 96,000 4.8 PEG/RBV/SOF 12 weeks 245,000 11.9 SOF/SMV 12 weeks 315,000 13.5 SOF/LDV 24 weeks 336,000 13.9
ICER a − dominated dominated 11,800 dominated − dominated 12,400 63,900 dominated − dominated dominated dominated 17,000 − 17,100 dominated dominated − 21,000 43,800 55,600
a
dominated = a strategy that provides lower QALE at either higher cost, or a higher cost per QALY gained.
Methods: Monte Carlo simulation of HCV disease comparing current U.S. FDA approved regimens for HCV genotype 1 infection. We stratified patients by treatment experience, cirrhosis status and HCV RNA to model appropriate treatment course. Treatment naïve patients (% SVR with/without cirrhosis, treatment course cost): 1. No treatment 2. Pegylated interferon (PEG) and ribavirin (RBV) 48 weeks (23/44%, $53,000) 3. PEG/RBV and simeprevir (SMV) 12 weeks (65/90%, $37,000) 4. PEG/RBV and sofosbuvir (SOF) 12 weeks (78/92%, $90,000) 5. SOF/ledipasvir (LDV) 8–12 weeks depending on cirrhosis and HCV RNA (96/96%, $58,000–87,000) Treatment experienced patients: 1. No treatment 2. PEG/RBV/SOF 12 weeks (74/92%, $53,000) 3. SOF/SMV 12 weeks (91/93%, $139,000)
4. SOF/LDV 12–24 weeks depending on cirrhosis (96%/96%, $87,000–175,000) In sensitivity analyses we considered only treating patients with SOF/LDV when they developed metavir F2 fibrosis. Results: Treatment naïve patients with and without cirrhosis: SOF/LDV increased QALE (0.5–9.1 QALY) and cost ($29,676-$68,118), resulting in ICERs $11,800–63,900/QALY (Table). Short SOF/LDV treatment (8 weeks) in non-cirrhotic patients with HCV RNA <6 million resulted in SOF/LDV being cost saving compared to other regimens. Treatment-experienced patients without cirrhosis: SOF/LDV was cost saving compared to other regimens. Treatment-experienced patients with cirrhosis: Compared to SOF/SMV 12 weeks, SOF/LDV 24 weeks increased cost by $20,975 and had an ICER <$100,000/QALY. Sensitivity analyses: Including the SOF/LDV F2 strategy did not change cost-effectiveness conclusions. Waiting for F2 disease resulted in lower QALE than treating all patients due to quality of life decrements while waiting for treatment and was a dominated strategy. Conclusions: SOF/LDV improves outcomes and has an ICER <$100,000/QALY for treatment naïve and experienced patients with and without cirrhosis. Limiting SOF/LDV access to only F2 disease results in lower QALE than simply treating all patients, at either higher total cost, or a higher cost per QALY gained. P0799 THE PHARMACOKINETICS OF BECLABUVIR (BMS-791325) WHEN ADMINISTERED IN COMBINATION WITH DACLATASVIR AND ASUNAPREVIR IN TREATMENT-NAIVE PATIENTS WITH OR WITHOUT CIRRHOSIS INFECTED WITH HCV GENOTYPE 1 B. He1 , K. Sims1 , E. Chung1 , W.-L. Luo1 , J. Pursley1 , M. Wind-Rotolo1 , F. LaCreta1 , R. Bertz1 , M. AbuTarif1 . 1 Research and Development, Bristol-Myers Squibb, Princeton, United States E-mail: [email protected] Background and Aims: Daclatasvir 30 mg (DCV; NS5A inhibitor), asunaprevir 200 mg (ASV; NS3 inhibitor), and beclabuvir 75 mg (BCV, BMS-791325; non-nucleoside NS5B inhibitor), administered twice daily (BID) as a fixed-dose combination (DCV/ASV/BCV) is currently in phase 3 development for the treatment of hepatitis C virus (HCV) infection. This DCV/ASV/BCV regimen administered for 12 weeks achieved a 100% sustained virologic response rate in HCV genotype (GT) 1-infected treatment-naive patients with compensated cirrhosis (Child–Pugh A) in an open-label, multipledose phase 2 study (AI443014); pharmacokinetics (PK) of DCV, ASV, BCV, and BMS-794712, an active metabolite of BCV in patients with and without cirrhosis are presented here. Methods: Patients (age, 18–70 years; BMI, 18–35 kg/m2 ) infected with HCV GT1 with (n = 8) or without (n = 73) biopsy-confirmed compensated cirrhosis (Child–Pugh A; capped at 10% of treatment group) received DCV/ASV/BCV for 12 weeks. Blood samples (0–12 h) were collected post-AM dose on days 1 and 14 from the first 20 non-cirrhotic patients and all cirrhotic patients for analysis by LC-MS/MS; standard non-compartmental PK parameters were calculated and summarized by descriptive statistics. Comparisons of (1) DCV and ASV PK descriptive statistics with PK data from Study AI447011 (DCV + ASV administered in combination in HCVinfected patients without cirrhosis), and (2) BCV and BMS-794712 PK descriptive statistics with PK data from Study AI443012 (BCV + pegIFNa/RBV in HCV-infected patients) will also be presented. In addition, data from patients receiving a DCV/ASV/BCV regimen containing BCV 150 mg BID will be presented. Results: BCV and BMS-794712 steady state exposures were similar between patients with and without compensated cirrhosis (Table). The results of DCV and ASV steady state exposures in cirrhotic versus non-cirrhotic patients were consistent with historical
Journal of Hepatology 2015 vol. 62 | S263–S864
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Cost
QALY
Naïve No Cirrhosis, RNA <6 Million (8 weeks SOF/LDV) No treatment 161,000 8.5 PEG/RBV 48 weeks 202,000 11.0 PEG/RBV/SMV 24 weeks 227,000 13.8 SOF/LDV 8 weeks 229,000 14.3 PEG/RBV/SOF 12 weeks 260,000 14.1 Naïve No Cirrhosis, RNA ≥6 Million (12 weeks SOF/LDV) No treatment 161,000 8.5 PEG/RBV 48 weeks 202,000 11.1 PEG/RBV/SMV 24 weeks 227,000 13.8 SOF/LDV 12 weeks 257,000 14.3 PEG/RBV/SOF 12 weeks 260,000 14.1 Naïve Cirrhosis (12 weeks SOF/LDV) No treatment 96,000 4.8 PEG/RBV 48 weeks 156,000 7.0 PEG/RBV/SMV 24 weeks 201,000 10.9 PEG/RBV/SOF 12 weeks 248,000 12.3 SOF/LDV 12 weeks 252,000 13.9 Experienced No Cirrhosis (12 weeks SOF/LDV) No treatment 160,000 8.5 SOF/LDV 12 weeks 259,000 14.3 PEG/RBV/SOF 12 weeks 261,000 14.1 SOF/SMV 12 weeks 324,000 14.1 Experienced Cirrhosis (24 weeks SOF/LDV) No treatment 96,000 4.8 PEG/RBV/SOF 12 weeks 245,000 11.9 SOF/SMV 12 weeks 315,000 13.5 SOF/LDV 24 weeks 336,000 13.9
ICER a − dominated dominated 11,800 dominated − dominated 12,400 63,900 dominated − dominated dominated dominated 17,000 − 17,100 dominated dominated − 21,000 43,800 55,600
a
dominated = a strategy that provides lower QALE at either higher cost, or a higher cost per QALY gained.
Methods: Monte Carlo simulation of HCV disease comparing current U.S. FDA approved regimens for HCV genotype 1 infection. We stratified patients by treatment experience, cirrhosis status and HCV RNA to model appropriate treatment course. Treatment naïve patients (% SVR with/without cirrhosis, treatment course cost): 1. No treatment 2. Pegylated interferon (PEG) and ribavirin (RBV) 48 weeks (23/44%, $53,000) 3. PEG/RBV and simeprevir (SMV) 12 weeks (65/90%, $37,000) 4. PEG/RBV and sofosbuvir (SOF) 12 weeks (78/92%, $90,000) 5. SOF/ledipasvir (LDV) 8–12 weeks depending on cirrhosis and HCV RNA (96/96%, $58,000–87,000) Treatment experienced patients: 1. No treatment 2. PEG/RBV/SOF 12 weeks (74/92%, $53,000) 3. SOF/SMV 12 weeks (91/93%, $139,000)
4. SOF/LDV 12–24 weeks depending on cirrhosis (96%/96%, $87,000–175,000) In sensitivity analyses we considered only treating patients with SOF/LDV when they developed metavir F2 fibrosis. Results: Treatment naïve patients with and without cirrhosis: SOF/LDV increased QALE (0.5–9.1 QALY) and cost ($29,676-$68,118), resulting in ICERs $11,800–63,900/QALY (Table). Short SOF/LDV treatment (8 weeks) in non-cirrhotic patients with HCV RNA <6 million resulted in SOF/LDV being cost saving compared to other regimens. Treatment-experienced patients without cirrhosis: SOF/LDV was cost saving compared to other regimens. Treatment-experienced patients with cirrhosis: Compared to SOF/SMV 12 weeks, SOF/LDV 24 weeks increased cost by $20,975 and had an ICER <$100,000/QALY. Sensitivity analyses: Including the SOF/LDV F2 strategy did not change cost-effectiveness conclusions. Waiting for F2 disease resulted in lower QALE than treating all patients due to quality of life decrements while waiting for treatment and was a dominated strategy. Conclusions: SOF/LDV improves outcomes and has an ICER <$100,000/QALY for treatment naïve and experienced patients with and without cirrhosis. Limiting SOF/LDV access to only F2 disease results in lower QALE than simply treating all patients, at either higher total cost, or a higher cost per QALY gained. P0799 THE PHARMACOKINETICS OF BECLABUVIR (BMS-791325) WHEN ADMINISTERED IN COMBINATION WITH DACLATASVIR AND ASUNAPREVIR IN TREATMENT-NAIVE PATIENTS WITH OR WITHOUT CIRRHOSIS INFECTED WITH HCV GENOTYPE 1 B. He1 , K. Sims1 , E. Chung1 , W.-L. Luo1 , J. Pursley1 , M. Wind-Rotolo1 , F. LaCreta1 , R. Bertz1 , M. AbuTarif1 . 1 Research and Development, Bristol-Myers Squibb, Princeton, United States E-mail: [email protected] Background and Aims: Daclatasvir 30 mg (DCV; NS5A inhibitor), asunaprevir 200 mg (ASV; NS3 inhibitor), and beclabuvir 75 mg (BCV, BMS-791325; non-nucleoside NS5B inhibitor), administered twice daily (BID) as a fixed-dose combination (DCV/ASV/BCV) is currently in phase 3 development for the treatment of hepatitis C virus (HCV) infection. This DCV/ASV/BCV regimen administered for 12 weeks achieved a 100% sustained virologic response rate in HCV genotype (GT) 1-infected treatment-naive patients with compensated cirrhosis (Child–Pugh A) in an open-label, multipledose phase 2 study (AI443014); pharmacokinetics (PK) of DCV, ASV, BCV, and BMS-794712, an active metabolite of BCV in patients with and without cirrhosis are presented here. Methods: Patients (age, 18–70 years; BMI, 18–35 kg/m2 ) infected with HCV GT1 with (n = 8) or without (n = 73) biopsy-confirmed compensated cirrhosis (Child–Pugh A; capped at 10% of treatment group) received DCV/ASV/BCV for 12 weeks. Blood samples (0–12 h) were collected post-AM dose on days 1 and 14 from the first 20 non-cirrhotic patients and all cirrhotic patients for analysis by LC-MS/MS; standard non-compartmental PK parameters were calculated and summarized by descriptive statistics. Comparisons of (1) DCV and ASV PK descriptive statistics with PK data from Study AI447011 (DCV + ASV administered in combination in HCVinfected patients without cirrhosis), and (2) BCV and BMS-794712 PK descriptive statistics with PK data from Study AI443012 (BCV + pegIFNa/RBV in HCV-infected patients) will also be presented. In addition, data from patients receiving a DCV/ASV/BCV regimen containing BCV 150 mg BID will be presented. Results: BCV and BMS-794712 steady state exposures were similar between patients with and without compensated cirrhosis (Table). The results of DCV and ASV steady state exposures in cirrhotic versus non-cirrhotic patients were consistent with historical
Journal of Hepatology 2015 vol. 62 | S263–S864
S633