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Chronic Hepatitis C: Do Generics Work as Well as Branded Drugs?

2017; Elsevier BV; Volume: 7; Issue: 3 Linguagem: Inglês

10.1016/j.jceh.2017.08.003

2213-3453

Madhumita Premkumar, Gagandeep Singh Grover, Radha K. Dhiman,

Liver Disease Diagnosis and Treatment

India has a large share of the hepatitis C virus (HCV) burden of the world. Unsafe medical practices and blood transfusions are the leading modes of transmission of HCV in India. The commonest HCV genotype in India is genotype 3 followed by genotype 1. While directly acting antivirals (DAAs) agents have become available at reasonable rates in India, cost of therapy remains a major barrier for control of HCV in India. Generic DAAs have been proven to be cost-saving in prior studies. We examined data from various studies in India and elsewhere using generic DAAs, and evaluated whether they are equally efficacious as the branded drugs. Since the availability of generic DAAs in the Indian market, there is a lot of real life data as well as prospective studies in special patient populations such as hematological disorders (thalassemia and hemophilia), chronic kidney disease, hemodialysis patients, post liver and renal transplant patients on immunosuppression, intravenous drug users, confections and other high risk groups. Control of HCV infection in India requires multi pronged approach. There is a need to formulate a health educational curriculum targeting not only the high-risk population but also the general population regarding the transmission of HCV. Adopting the dual approach of treating the old cases (decreasing the reservoir pool of HCV) and decreasing the incidence of new ones would help curtail the disease and decrease liver related mortality. In this scenario, the role of efficacious low cost generic medications is essential. India has a large share of the hepatitis C virus (HCV) burden of the world. Unsafe medical practices and blood transfusions are the leading modes of transmission of HCV in India. The commonest HCV genotype in India is genotype 3 followed by genotype 1. While directly acting antivirals (DAAs) agents have become available at reasonable rates in India, cost of therapy remains a major barrier for control of HCV in India. Generic DAAs have been proven to be cost-saving in prior studies. We examined data from various studies in India and elsewhere using generic DAAs, and evaluated whether they are equally efficacious as the branded drugs. Since the availability of generic DAAs in the Indian market, there is a lot of real life data as well as prospective studies in special patient populations such as hematological disorders (thalassemia and hemophilia), chronic kidney disease, hemodialysis patients, post liver and renal transplant patients on immunosuppression, intravenous drug users, confections and other high risk groups. Control of HCV infection in India requires multi pronged approach. There is a need to formulate a health educational curriculum targeting not only the high-risk population but also the general population regarding the transmission of HCV. Adopting the dual approach of treating the old cases (decreasing the reservoir pool of HCV) and decreasing the incidence of new ones would help curtail the disease and decrease liver related mortality. In this scenario, the role of efficacious low cost generic medications is essential. The prevalence of hepatitis C virus (HCV) infection is estimated to be more than 70 million people worldwide and between 6 and11 million in India.1Dhiman R.K. Future of therapy for hepatitis C in India: a matter of accessibility and affordability?.J Clin Exp Hepatol. 2014; 4: 85-86Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Chronic HCV infection is one of the prevalent causes of the disease burden of cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths in India. Untreated HCV infection also leads to substantial economic burden and a hidden social cost.2Saraswat V. Norris S. de Knegt R.J. et al.Historical epidemiology of hepatitis C virus (HCV) in select countries – volume 2.J Viral Hepat. 2015; 22: 6-25Crossref PubMed Scopus (85) Google Scholar Despite a low to moderate (1–1.5%) prevalence of HCV, India accounts for a significant share of global HCV infections due to the large population; approximately 12–18 million population is infected with HCV. In 2015, about 60,000 deaths were reported to be related to HCV alone in India.3Stanaway J.D. Flaxman A.D. Naghavi M. et al.The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.Lancet (London, England). 2016; 388: 1081-1088Abstract Full Text Full Text PDF PubMed Scopus (908) Google Scholar New directly acting antivirals (DAAs) for HCV treatment are efficacious, providing rates of sustained virological response (SVR) exceeding 95%.4Puri P. Anand A.C. Saraswat V.A. et al.Disease burden of chronic hepatitis C virus (HCV) infection in India.Hepatology. 2014; 60: 937A-938AGoogle Scholar However the patented drugs are expensive limiting treatment to those with advanced disease. Thus, these drugs offer a hope of reducing the burden of HCV, reducing disease transmission and complications of liver disease. Hence, in India a dual approach reducing incidence and increasing treatment is appropriate in showing short-term improvements in advanced stage outcomes with reductions in prevalence.1Dhiman R.K. Future of therapy for hepatitis C in India: a matter of accessibility and affordability?.J Clin Exp Hepatol. 2014; 4: 85-86Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar However, these drugs are very costly in several countries.5Puri P. Anand A.C. Saraswat V.A. et al.Consensus statement of HCV task force of the Indian National Association for Study of the Liver (INASL). Part I: Status report of HCV infection in India.J Clin Exp Hepatol. 2014; 4: 104-114Abstract Full Text Full Text PDF Scopus (31) Google Scholar In India, the three DAAs [sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir (DCV)] are available from several generic manufacturers at a price as low as $110 for 12 weeks therapy.6Iyengar S. Tay-Teo K. Vogler S. et al.Prices, costs, and affordability of new medicines for hepatitis C in 30 countries: an economic analysis.PLoS Med. 2016; 13 (PMID:27243629): e1002032Crossref PubMed Scopus (187) Google Scholar This is in stark contrast to the cost of 12-week sofosbuvir therapy being approximately US $42,017, ranging from US $37,729 in Japan to US$64,680 in the United States.5Puri P. Anand A.C. Saraswat V.A. et al.Consensus statement of HCV task force of the Indian National Association for Study of the Liver (INASL). Part I: Status report of HCV infection in India.J Clin Exp Hepatol. 2014; 4: 104-114Abstract Full Text Full Text PDF Scopus (31) Google Scholar In a recent report, the use of generic DAAs in Indian hepatitis C patients was reported to increase the life expectancy by 8.02 years, increase quality-adjusted life years (QALYs) by 3.89, avert 19.07 disability-adjusted life years (DALYs), and reduce the lifetime healthcare costs by $1309 per-person treated, when compared with untreated HCV infected patients.7Aggarwal R. Chen Q. Goel A. et al.Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.PLOS ONE. 2017; https://doi.org/10.1371/journal.pone.0176503Crossref Scopus (73) Google Scholar Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation in all subjects and within 5 years in patients with cirrhosis.7Aggarwal R. Chen Q. Goel A. et al.Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.PLOS ONE. 2017; https://doi.org/10.1371/journal.pone.0176503Crossref Scopus (73) Google Scholar Almost all published cost and efficacy analyses have been conducted in developed nations under patent rules where DAAs have a prohibitive cost limiting widespread use.9Chhatwal J. He T. Lopez-Olivo M.A. Systematic review of modelling approaches for the cost effectiveness of hepatitis C treatment with direct-acting antivirals.Pharmacoeconomics. 2016; 34: 551-567Crossref PubMed Scopus (64) Google Scholar, 10Linas B.P. Barter D.M. Morgan J.R. et al.The cost-effectiveness of sofosbuvir-based regimens for treatment of hepatitis C virus genotype 2 or 3 infection.Ann Intern Med. 2015; 162: 619-629Crossref PubMed Scopus (25) Google Scholar, 11Najafzadeh M. Andersson K. Shrank W.H. et al.Cost-effectiveness of novel regimens for the treatment of hepatitis C virus.Ann Intern Med. 2015; 162: 407-419Crossref PubMed Scopus (179) Google Scholar The efficacy of generic DAA is under scrutiny, and in this study we report the pooled data from different trials in India and elsewhere using sourced generic DAA therapy. We found generic DAA to be cost-effective in view of low treatment prices and also be cost-saving in terms of improvement of both public health burden and economic cost perspective. The Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) is a public health initiative by the government of Punjab to tackle the HCV burden in the state (http://pbhealth.gov.in/SOPs%20for%20MMPHCRF.pdf).12Dhiman R.K. Satsangi S. Grover G.S. Puri P. Tackling the hepatitis C disease burden in Punjab, India.J Clin Exp Hepatol. 2016; 6: 224-232Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar The results from this treatment program will drive physicians and public health professionals toward central funding of HCV treatment, and may make it easier for health administrators and political leaders take an informed decision. We therefore estimated the efficacy of treatment of HCV-infected persons in India and elsewhere using low-priced DAAs, and evaluated the results from various published and unpublished clinical data from different centers across the country. This question is also of interest for other countries where it may be possible to obtain DAAs at low prices. In India, pegylated interferon alfa (Peg-IFNα) plus ribavirin (RBV) combination therapy has been replaced by DAAs. These drugs have lower side effects, better tolerability, and are simpler to administer. In view of their potential efficacy and safety (SVR > 90% in most studies), DAAs have the potential to eliminate one of the most common causes of liver related morbidity and mortality.12Dhiman R.K. Satsangi S. Grover G.S. Puri P. Tackling the hepatitis C disease burden in Punjab, India.J Clin Exp Hepatol. 2016; 6: 224-232Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar The nucleoside non-structural protein non-structural (NS) 5B inhibitor SOF became available in India in March 2015, which was followed in 2016 by the NS5A replication complex inhibitors, LDV and DCV. Velpatasvir (VEL), a pangenotypic DAA, is now available in India and the Indian National Association for Study of the Liver (INASL) guidelines are accordingly going to be updated. The INASL guidelines are based on considerations for the treatment of HCV in India including the cost of therapy, the poorer response of the predominant genotype (GT 3) and the non-availability of many of the DAA recommended by other guidelines.4Puri P. Anand A.C. Saraswat V.A. et al.Disease burden of chronic hepatitis C virus (HCV) infection in India.Hepatology. 2014; 60: 937A-938AGoogle Scholar, 5Puri P. Anand A.C. Saraswat V.A. et al.Consensus statement of HCV task force of the Indian National Association for Study of the Liver (INASL). Part I: Status report of HCV infection in India.J Clin Exp Hepatol. 2014; 4: 104-114Abstract Full Text Full Text PDF Scopus (31) Google Scholar The widespread uptake of DAA in India is possible, as these have so far been marketed at a fraction of the cost in the west. Aggarwal et al.7Aggarwal R. Chen Q. Goel A. et al.Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.PLOS ONE. 2017; https://doi.org/10.1371/journal.pone.0176503Crossref Scopus (73) Google Scholar have presented a model for healthcare payer's perspective. For effectiveness outcomes, they used QALYs, a commonly used metric in cost-effectiveness analysis, and DALYs, as recommended by the WHO. The cost of SOF/LDV (with or without RBV), or SOF/DCV combination treatment was taken as Indian Rupees (INR)approximately 6711 (USD 100) for every 28 days’ supply. The costs of pre-treatment testing (for disease staging and HCV genotyping) were taken as INR 8000 (approximately USD 119), and those for tests while on and after treatment were taken as INR 6000 (approximately USD 89). The authors presented a minimalistic cost model representing a conservative scenario by underestimating the savings resulting from DAA use; however, this was supplemented by sensitivity analyses using a wide range of costs.7Aggarwal R. Chen Q. Goel A. et al.Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.PLOS ONE. 2017; https://doi.org/10.1371/journal.pone.0176503Crossref Scopus (73) Google Scholar A recent pharmacoeconomic study established that the use of generic DAAs in Indian HCV patients would increase the life expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce the lifetime healthcare costs. Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation overall and within 5 years in persons with cirrhosis.8Westerhout K. Treur M. Mehnert A. Pascoe K. Ladha I. Belsey J. A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service.J Med Econ. 2015; 18: 838-849Crossref PubMed Scopus (13) Google Scholar, 9Chhatwal J. He T. Lopez-Olivo M.A. Systematic review of modelling approaches for the cost effectiveness of hepatitis C treatment with direct-acting antivirals.Pharmacoeconomics. 2016; 34: 551-567Crossref PubMed Scopus (64) Google Scholar The high cost of patented DAA drugs needs to be reevaluated in the setting of cheaper and efficacious generic alternatives. The business model relies on using patent protection laws against free market competition with little revenue being directed at new drug research, with more stress on drug marketing (25% of revenues) rather than new drug discovery (1.3% of revenues).10Linas B.P. Barter D.M. Morgan J.R. et al.The cost-effectiveness of sofosbuvir-based regimens for treatment of hepatitis C virus genotype 2 or 3 infection.Ann Intern Med. 2015; 162: 619-629Crossref PubMed Scopus (25) Google Scholar Generic versions of DAAs are manufactured in India under voluntary license from Gilead Sciences, and by other Indian companies who are not licensees, and in other countries which are not bound by patent law. In many countries it is legal to import drugs for personal use by ordering them online. In other countries imports of generic drugs are restricted to those carried through customs by individuals in quantities sufficient for personal use. Hence over the last two years a large pool of data has emerged from India, the Middle Eastern countries and also ‘buyers’ clubs’ in the west using imported generic medicines.13Mehta R. Kabrawala M. Nandwani S. et al.Efficacy and safety of sofosbuvir-based therapy for chronic hepatitis C infection in “real-life” cohort.Indian J Gastroenterol. 2016; 35: 459-464Crossref PubMed Scopus (7) Google Scholar Bioequivalence studies also establish efficacy of generic medications. A test group of 25–50 subjects takes a single dose of originator medication, and the blood levels of the drug(s) are measured at various time points over the next 24 h. After a washout period, the same group then takes the generic version and once again the blood levels of the drug(s) are measured. A drug is deemed bioequivalent when the blood levels at all time points are a statistically near identical match. Bioequivalence proves, not only do the tablets contain the active ingredient(s) in the correct quantity, but more importantly that they deliver these into the patient's system in a similar fashion to the originator version.14Ghinea N. Lipworth W. Day R. Hill A. Dore G. Danta M. Importation of generic hepatitis C therapies: bridging the price – access gap in high-income countries.Lancet. 2017; 389: 1268-1272Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Preliminary reports of the generic DAA have shown reasonable results (Table 1).Table 1Efficacy and Safety of Sofosbuvir-based Therapy for Chronic Hepatitis C Infection in “Real-Life” Cohort in India.Author/yearnStudy typePrimary end point(SVR 12)Adverse eventsMehta R et al., 201613Mehta R. Kabrawala M. Nandwani S. et al.Efficacy and safety of sofosbuvir-based therapy for chronic hepatitis C infection in “real-life” cohort.Indian J Gastroenterol. 2016; 35: 459-464Crossref PubMed Scopus (7) Google Scholar107Observational study;SOF and RBV with or without Peg-IFNOverall—94.3% (99/105)GT3—92.5% (62/67)GT1—97.4% (37/38)29.9%Satsangi S et al., 201615Satsangi S. Mehta M. Duseja A. Taneja S. Dhiman R.K. Chawla Y. Dual treatment with sofosbuvir plus ribavirin is as effective as triple therapy with pegylated interferon plus sofosbuvir plus ribavirin in predominant genotype 3 patients with chronic hepatitis C.J Gastroenterol Hepatol. 2016; https://doi.org/10.1111/jgh.13595Crossref Scopus (18) Google Scholar158[TN = 128 (89%), TE = 30 (19%)]Observational study;SOF and RBV with or without Peg-IFNOverall—98.7% (156/158)GT3—99.3% (134/135)GT1—97.5% (39/40)SOF + RBV = 9.7%SOF + RBV + Peg-IFN = 32.7%Shah SR et al., 201616Shah S.R. Chowdhury A. Mehta R. et al.Sofosbuvir plus ribavirin in treatment-naïve patients with chronic hepatitis C virus genotype 1 or 3 infection in India.J Viral Hepat. 2016; https://doi.org/10.1111/jvh.12654Crossref PubMed Scopus (14) Google Scholar117Observational study;SOF and RBVGT1—90% (95% CI, 73–98) and 96% (95% CI, 82–100) of patients following 16 and 24 weeks of treatmentGT3—100% (95% CI, 88–100) and 93% (95% CI, 78–99) after 16 and 24 weeks of therapyMild or moderate in severity, occurred in 69% and 57% of patients receiving 16 and 24 weeks of treatment, respectivelySood A et al., 201617Sood A. Midha V. Mahajan R. et al.Results of Sofosbuvir based combination therapy for chronic hepatitis C cohort of Indian patients in real life clinical practice.J Gastroenterol Hepatol. 2016; https://doi.org/10.1111/jgh.13628Crossref Scopus (17) Google Scholar736[GT3 (80%), GT1 (14.7%), GT4 (4.9%). Cirrhosis—330 (44.8%) (CTP-A 75.8%; CTP B 18%; CTP C: 6%).]Observational study;GT1, GT4 and GT5—SOF and RBV with PeGT-IFN and GT3—SOF and RBV with Peg-IFNOverall—95.8% (453/473)GT1—97.0% (97/100)GT3—95.6% (563/571)GT4—93.1% (27/29)Noncirrhotics ≫cirrhotics (P = 0.003)CC ≫ DC (P = 0.0018)Triple therapy ≫ dual therapyDhiman RK and Grover GS, 2017 (Unpublished)18Dhiman R.K. Grover G.S. MMPHCRF.2017Google Scholarn = 11105Noncirrhotic—10219Cirrhotic—886Prospective observational study (MMPHCRF); Public health care setting.Non-cirrhotic: GT1 to GT4—SOF + DCV for 12 weeks.Cirrhotic:GT1 and GT4—SOF + DCV + RBV for 12 weeks or Sofo + Dacla for 24 weeksGT3—SOF + DCV + RBV for 24 weeksNoncirrhotic—92.5%Cirrhotic—92.7%GT3—92.6%Nongenotype 3—93.1%Goel A et al., 201719Goel A. Bhadauria D.S. Kaul A. et al.Experience with direct acting anti-viral agents for treating hepatitis C virus infection in renal transplant recipients.Indian J Gastroenterol. 2017; 36: 137-140Crossref PubMed Scopus (20) Google Scholar160 patients (90% TN; CHC 49%, CC 32%, and DC 19%),39 (24%) received Peg-IFN, sofosbuvir and ribavirin, 21 (13%) received sofosbuvir and ribavirin, and 100 (63%) received SOF and DCV, with or without RBV.On intention-to-treat basis, RVR, ETR, and SVR12 –146/160 (91.3%), 151/160 (94.4%), and 147/160 (91.9%), respectivelyDual-DAA-based regimens were safe and highly effective in treating genotype-3 HCV infection in CHC and CC patientsSidhu et al., 201720Sidhu S.S. Malhi N.S. Goyal O. et al.Treatment of chronic hepatitis C genotype 3 with Sofosbuvir-based therapy: a real-life study.Hepatol Int. 2017; 11: 277-285https://doi.org/10.1007/s12072-017-9794-1Crossref PubMed Scopus (5) Google ScholarCHC -G3 (n = 931)Group 1; Dual therapy (n = 432) = SOF 400 mg + weight-based RBV, daily × 24 weeksGroup 2; Triple therapy (n = 499)—Peg-IFNα 2a 180 mcg weekly, SOF 400 mg plus weight-based RBV, daily × 12 weeksOverall SVR rates were 91 and 92% in the dual and triple therapy arms.In non cirrhotics,Dual therapy: SVR in TE was 67% and 74% in TN.In cirrhotics SVR was 44% (dual therapy) and 58% (triple therapy)Triple therapy: SVR 50% in TE and 97% in TNTriple therapy was more efficacious especially in TE or cirrhotic patients.CI, confidence intervals; CHC, chronic hepatitis C; CC, compensated cirrhosis; DC, decompensated cirrhosis; CTP, Child Turcotte Pugh; SVR 12, sustained virological response 12 weeks; GT, genotype; Peg-IFNα, pegylated interferon-α; SOF, sofosbuvir; RBV, ribavirin; RVR, rapid virological response; DCV, daclatasvir; LDV, Ledipasvir; MMPHCRF, Mukh Mantri Punjab Hepatitis C Relief Fund; TE, treatment experienced; TN, treatment naïve. Open table in a new tab CI, confidence intervals; CHC, chronic hepatitis C; CC, compensated cirrhosis; DC, decompensated cirrhosis; CTP, Child Turcotte Pugh; SVR 12, sustained virological response 12 weeks; GT, genotype; Peg-IFNα, pegylated interferon-α; SOF, sofosbuvir; RBV, ribavirin; RVR, rapid virological response; DCV, daclatasvir; LDV, Ledipasvir; MMPHCRF, Mukh Mantri Punjab Hepatitis C Relief Fund; TE, treatment experienced; TN, treatment naïve. Hill et al reported people who purchased the drugs were cured of hepatitis C at a cost of around $700–$900 in South-East Asia and Eastern Europe. The price of treatment remains a major barrier to curing hepatitis C for millions of people, and where rationing of treatment, lack of health insurance or lack of a national treatment program deny access to these drugs, people are turning to internet-based community portals or ‘buyer's clubs’ to obtain generic versions of direct-acting antivirals.20Sidhu S.S. Malhi N.S. Goyal O. et al.Treatment of chronic hepatitis C genotype 3 with Sofosbuvir-based therapy: a real-life study.Hepatol Int. 2017; 11: 277-285https://doi.org/10.1007/s12072-017-9794-1Crossref PubMed Scopus (5) Google Scholar, 21Hill A. Simmons B. Gotham D. Fortunak J. Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C.J Virus Erad. 2016; 2: 28-31Crossref PubMed Google Scholar, 22Andrieux-Meyer I. Cohn J. Affonso de Araujo E. Hamid S. Disparity in market prices for hepatitis C virus direct-acting drugs.Lancet. 2015; 3: e676-e677PubMed Scopus (63) Google Scholar, 23Freeman J. Reviewing DAA Efficacy Managing Patient Treatment In Online Neighborhoods (REDEMPTION). National Library of Medicine, USA, Bethesda, MD2016Google Scholar Freeman et al.23Freeman J. Reviewing DAA Efficacy Managing Patient Treatment In Online Neighborhoods (REDEMPTION). National Library of Medicine, USA, Bethesda, MD2016Google Scholar showed very high cure rates when using generic versions of direct-acting antivirals, and also provided evidence that the products purchased contained the necessary levels of active drug. The studies presented this week, in which data supplied by patients and their physicians were analyzed by St Stephen's AIDS Trust in London, measured virological responses. Two studies identified the generic products used, and one study was able to measure levels of active ingredients. The preliminary results of the three studies show cure rates comparable to those achieved with branded products. The REDEMPTION-1 trial data presented at European Association for the Study of the Liver (EASL) International Liver Congress (ILC) 2016 clearly demonstrates that the safety and efficacy of generics, at least the generics used in the study, are equivalent to the originator medications and deliver the expected 90%+ sustained virological response (SVR) rates. The REDEMPTION trial evaluated pooled data of 1160 patients with sourced generic SOF, LDV, DCV, VEL and RBV from suppliers in India, Bangladesh, China and Egypt at 240 locations in 88 countries spanning 5 continents.23Freeman J. Reviewing DAA Efficacy Managing Patient Treatment In Online Neighborhoods (REDEMPTION). National Library of Medicine, USA, Bethesda, MD2016Google Scholar, 24Freeman J. Sallie R. Kennedy A. Hieu P.T. Jeffreys G. Hill A.M. High sustained virological response rates using generic Direct Acting Antiviral treatment for hepatitis C, imported into Australia.J Hepatol. 2016; 2: S209Abstract Full Text PDF Google Scholar In addition to routine assessment, HCV RNA load was estimated at baseline, on treatment, and post treatment for SVR4, SVR12 and SVR24. The data provided clues to two pertinent questions raised about the quality and efficacy of generic drugs and also safety in terms of adverse events.24Freeman J. Sallie R. Kennedy A. Hieu P.T. Jeffreys G. Hill A.M. High sustained virological response rates using generic Direct Acting Antiviral treatment for hepatitis C, imported into Australia.J Hepatol. 2016; 2: S209Abstract Full Text PDF Google Scholar, 25EASL press release. Low-cost generic direct-acting antiviral treatment for hepatitis C is equivalent to branded formulations: New data indicate that generics are a feasible alternative to support access to direct-acting antiviral treatment for hepatitis C sufferers. 16.04.16. http://www.eurekalert.org/pub_releases/2016-04/eaft-lgd040816.php#.VxH_PRMb3Io.Google Scholar, 26Freeman J.A.D. Hill A. The use of generic medications for hepatitis C.Liver Int. 2016; 36: 929-932https://doi.org/10.1111/liv.13157Crossref PubMed Scopus (21) Google Scholar The FixHepC is an online service which directs people toward generic sources of hepatitis C drugs and arranges testing of the drugs to ensure that they contain the correct levels of active ingredients. Freeman et al.23Freeman J. Reviewing DAA Efficacy Managing Patient Treatment In Online Neighborhoods (REDEMPTION). National Library of Medicine, USA, Bethesda, MD2016Google Scholar presented data on extended follow-up on 438 of the 448 patients at the International Liver Congress in 2016. Fifty-nine per cent of patients contributing data to this study had less advanced fibrosis (F0-F2), 11% had F3 fibrosis and 27% had cirrhosis. Analysis of SVR 12 responses by genotype showed that patients with GT 3 were substantially less likely to achieve a SVR compared to other genotypes. Eighty per cent of GT 3 patients, predominantly treated with SOF/DCV, achieved SVR 12, compared to 94% of genotype 1 patients and all patients with genotypes 2, 4, 5 and 6. Overall, 90% of patients who had obtained drugs through the FixHepC Buyer's Club and who had completed the 12-week post-treatment follow-up have achieved SVR 12 to date.27FixHepC. Cure hepatitis C with sofosbuvir ledipasvir daclatasvir. http://fixhepc.com/ Accessed 14.08.17.Google Scholar, 28Hill A. Gotham D. Fortunak J. Significant reductions in costs of generic production of sofosbuvir and daclatasvir for hepatitis C treatment in low- and middle-income countries.J Hepatol. 2016; 2: S209Google Scholar In Thailand a 12-week course of Sovaldi and Daklinza costs around $10,000, and is similarly priced in most other countries in the region. A new web based portal directs people to online pharmacies in India to purchase generic versions of SOF and either LDV or DCV. In this data set, 237 patients were on treatment. SVR 4 results are available for 33 patients and SVR12 results for 24. Results to date show that one patient failed to achieve rapid virologic response on SOF/RBV, and one patient failed to achieve an end-of-treatment virologic response on SOF/LDV. Two patients on SOF/RBV experienced virologic rebound between weeks 4 and 12 post-treatment, resulting in a 85% SVR 12 rate to date on this combination. All other patients who have reached 12-week post-treatment follow-up have achieved SVR.29Korologou-Linden R. et al.Efficacy of generic direct acting antiviral treatment for hepatitis C, imported into South-East Asia and China. International Congress on Drug Therapy in HIV Infection (HIV Glasgow), Glasgow, Poster 262, 2016.J Int AIDS Soc. 2016; 19 (P262): 21487https://doi.org/10.7448/IAS.19.8.21487Crossref PubMed Google Scholar The Russian hepatitis C treatment program does not offer sofosbuvir yet, and private treatment with the drug costs around $9500 for a 12-week course of treatment. Again community based platforms for treatment have been set up such as the Gepatikta group which offers therapy at a cost of around $700–$900 per treatment course by sourcing drugs from India and China. The collected data from this treatment program were assembled from private physicians and AIDS clinics in Russia, Estonia, Israel, Belarus, and Ukraine. About 56% of patients in this cohort had genotype 3 infection, and 41% had genotype 1 infection. As expected virological responses were poorer in genotype 3 patients. At week 2, the rates of RVR (HCV RNA < 25 IU/ml) were GT 3(82%), GT 1(90%) and GT 2(88%). Difficulties with making comparisons across these cohort data is that due to heterogeneity of collection from different sources, there may be loss of follow up, and missed measurements. Longer-term follow-up of these large groups of patients will be needed in order to produce more robust estimates of the proportions achieving SVR12, as well as any consistent differences by genotype (Table 2).30Hill A. et al.Efficacy of generic direct acting antiviral treatment for hepatitis C, imported into Russia and Eastern Europe. International Congress on Drug Therapy in HIV Infection (HIV Glasgow), Glasgow, Poster P261, 2016.J Int AIDS Soc. 2016; 19 (P261): 21487https://doi.org/10.7448/IAS.19.8.21487Crossref PubMed Google ScholarTable 2Real Life Data From Different Treatment Cohorts Using Generic Drugs Outside India.Author/yearnStudy typePrimary end point (SVR 12)Salient resultsQing-Lei Zeng et al. 201731Zeng Q.L.