Affordable treatment and political commitment are crucial to eliminate hepatitis C globally

Abstract

It has been nearly 10 years since highly effective, all-oral, direct-acting antiviral (DAA) treatments triggered a revolution in hepatitis C care and treatment. DAAs led to optimism that hepatitis C could be eliminated, and in 2016 WHO set targets to eliminate hepatitis C as a public health threat by 2030. Specifically, WHO called for an 80% reduction in new chronic infections and a 65% reduction in mortality from that reported in 2015.1WHOGlobal health sector strategy on viral hepatitis 2016-2021. WHO, Geneva2016Google Scholar However, many countries are likely to miss these targets,2Razavi H Sanchez Gonzalez Y Yuen C Cornberg M Global timing of hepatitis C virus elimination in high-income countries.Liver Int. 2020; 40: 522-529Crossref PubMed Scopus (101) Google Scholar with the COVID-19 pandemic worsening matters.Many countries' hepatitis C elimination efforts are lagging because of the cost of DAAs. Although their price has reduced markedly since they first came onto the market (approximately US$1000 per pill) in 2014, treatment remains unaffordable for many people. In high-income countries with strong public health systems or comprehensive insurance programmes, the price of treatment has been negotiated to a cost that enables the population to access care; however, in many other high-income countries, treatment remains unaffordable, presenting a major barrier to scale-up.3WHOAccelerating access to hepatitis C diagnostics and treatment: overcoming barriers in low- and middle-income countries. WHO, Geneva2021Google Scholar In low-income and middle-income countries (LMICs), voluntary licensing and the Medicine Patent Pool has enabled access to DAAs at less than $60 per treatment course, and, in certain countries, patents for some DAAs have allowed generic manufacturers to set up local production without a license.3WHOAccelerating access to hepatitis C diagnostics and treatment: overcoming barriers in low- and middle-income countries. WHO, Geneva2021Google Scholar However, as highlighted by Isabelle Andrieux-Meyer and colleagues4Andrieux-Meyer I Tan S-S Thanprasertsuk S et al.Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.Lancet Gastroenterol Hepatol. 2021; (published online April 15.)https://doi.org/10.1016/S2468-1253(21)00031-5Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar in The Lancet Gastroenterology & Hepatology, nearly 50 middle-income countries, estimated to have 43% of the global hepatitis C burden, have been excluded from the license agreements of originator companies for key DAAs, making treatment unaffordable for most of their citizens.In an effort to address this crucial issue of treatment affordability, Andrieux-Meyer and colleagues4Andrieux-Meyer I Tan S-S Thanprasertsuk S et al.Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.Lancet Gastroenterol Hepatol. 2021; (published online April 15.)https://doi.org/10.1016/S2468-1253(21)00031-5Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar studied the efficacy and safety of ravidasvir plus sofosbuvir in people with chronic hepatitis C. Ravidasvir is a non-structural protein 5A inhibitor supported by the Drugs for Neglected Diseases initiative in the hope of providing an affordable pangenotypic regimen when used in combination with sofosbuvir. STORM-C-1 is the first part of an open-label, single-arm clinical trial with 301 participants in Malaysia and Thailand (98 [33%] with genotype 1a, 27 [9%] with genotype 1b, two [1%] with genotype 2, 158 [52%] with genotype 3, and 16 [5%] with genotype 6), of whom 81 (27%) had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had previous interferon-based treatment. Key findings in this interim analysis were an overall sustained virological response at 12 weeks after treatment (SVR12) of 97%, an SVR12 of 97% in participants with genotype 3 (a subgroup of patients who have lower SVR12 with some regimens), and an SVR of 96% for participants with cirrhosis. SVR12 rates were unaffected by HIV co-infection or previous interferon treatment history.4Andrieux-Meyer I Tan S-S Thanprasertsuk S et al.Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.Lancet Gastroenterol Hepatol. 2021; (published online April 15.)https://doi.org/10.1016/S2468-1253(21)00031-5Summary Full Text Full Text PDF PubMed Scopus (7) Google ScholarThe outcomes of STORM-C-1 are encouraging. ravidasvir appears to be an affordable option that could help reduce treatment costs, particularly in middle-income countries that are stuck in the middle—ineligible for the licensed generic drugs but unable to afford current pangenotypic regimens.5Schröeder SE Pedrana A Scott N et al.Innovative strategies for the elimination of viral hepatitis at a national level: a country case series.Liver Int. 2019; 39: 1818-1836Crossref PubMed Scopus (29) Google Scholar However, STORM-C-1 had some limitations. It excluded participants who reported current injecting drug use and hepatitis B co-infection; additionally, SVR12 was lower in those with genotype 6, and no participants had genotype 4. Of note, in a previous study from Egypt examining the efficacy of ravidasvir and sofosbuvir with or without ribavirin, participants with genotype 4 HCV infection had high SVR12 rates.6Esmat G Elbaz T El Raziky M et al.Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4.J Hepatol. 2018; 68: 53-62Summary Full Text Full Text PDF Scopus (14) Google ScholarAlthough the cost of DAA treatment is important, achieving the WHO 2030 elimination targets requires more than affordable treatment. The availability and affordability of diagnostics remains a major barrier to treatment scale-up, particularly in LMICs. In 2020, prices were $1–8 per test for WHO-prequalified HCV antibody rapid diagnostic tests, but many countries cannot purchase rapid diagnostic tests so cheaply.3WHOAccelerating access to hepatitis C diagnostics and treatment: overcoming barriers in low- and middle-income countries. WHO, Geneva2021Google Scholar Moreover, many health systems require restructuring to meet the needs of individuals who require care; this includes moving care into community settings, supporting task-shifting to reduce reliance on doctors and other highly qualified but few in number medical personnel, and reducing numbers of clinic visits through simplified testing, including point-of-care testing.7Pedrana A Howell J Scott N et al.Global hepatitis C elimination: an investment framework.Lancet Gastroenterol Hepatol. 2020; 5: 927-939Summary Full Text Full Text PDF PubMed Scopus (17) Google ScholarFinite resources mean countries must make difficult choices as they work to achieve universal health coverage, a target for 2030 in the UN Sustainable Development Goals.8The WHO Consultative Group on Equity and Universal Health CoverageMaking fair choices on the path to universal health coverage. Final report of the WHO Consultative Group on Equity and Universal Health Coverage. WHO, Geneva2014Google Scholar Countries are advised to identify which interventions to prioritise in their national health benefits package. In making decisions about the composition of health benefits packages, WHO recommends prioritising interventions using three criteria: cost-effectiveness, priority to the worst off, and financial risk protection.9Scott N Kuschel C Pedrana A et al.A model of the economic benefits of global hepatitis C elimination: an investment case.Lancet Gastroenterol Hepatol. 2020; 5: 940-947Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar Lowering the cost of treatment through the availability of drugs, such as ravidasvir, is important to improve cost-effectiveness. However, it also requires political commitment to negotiate and address regulatory and intellectual property barriers. An example of such an approach is in Malaysia, where there has been strong political commitment to support public health programmes and to make HCV treatment available and affordable for the population. Pharco (Alexandria, Egypt) has committed to making the ravidasvir and sofosbuvir combination, once approved, available at a price of $300 or less per treatment course,10Drugs for Neglected Diseases InitiativeDrugs for Neglected Diseases Initiative and Pharco pharmaceuticals to test affordable hepatitis C regimen with support of Malaysian and Thai governments.https://dndi.org/press-releases/2016/dndi-pharco-hepc-malaysia-thailand/Date: 2016Date accessed: April 13, 2021Google Scholar representing a hundredth the cost of the existing originator DAA regimen.Countries also need high-quality surveillance data to identify which health interventions to prioritise and include in their health benefits package. Absent in many countries, high-quality data about hepatitis C is crucial to enable countries to measure and understand the financial risk associated with the direct and indirect costs of hepatitis C morbidity and mortality. Doing nothing has real but often unrecognised costs. The paucity of data, combined with concern about costs, could prevent many countries from meeting the 2030 hepatitis C elimination targets, despite the demonstrable economic benefits of doing so.9Scott N Kuschel C Pedrana A et al.A model of the economic benefits of global hepatitis C elimination: an investment case.Lancet Gastroenterol Hepatol. 2020; 5: 940-947Summary Full Text Full Text PDF PubMed Scopus (16) Google ScholarMH and AP leads research that receives investigator-initiated research funding from Gilead Sciences, AbbVie, and Merck Sharp & Dohme. AP reports travel honoraria and consultancy fees from Gilead Sciences outside the submitted work. BD declares no competing interests. It has been nearly 10 years since highly effective, all-oral, direct-acting antiviral (DAA) treatments triggered a revolution in hepatitis C care and treatment. DAAs led to optimism that hepatitis C could be eliminated, and in 2016 WHO set targets to eliminate hepatitis C as a public health threat by 2030. Specifically, WHO called for an 80% reduction in new chronic infections and a 65% reduction in mortality from that reported in 2015.1WHOGlobal health sector strategy on viral hepatitis 2016-2021. WHO, Geneva2016Google Scholar However, many countries are likely to miss these targets,2Razavi H Sanchez Gonzalez Y Yuen C Cornberg M Global timing of hepatitis C virus elimination in high-income countries.Liver Int. 2020; 40: 522-529Crossref PubMed Scopus (101) Google Scholar with the COVID-19 pandemic worsening matters. Many countries' hepatitis C elimination efforts are lagging because of the cost of DAAs. Although their price has reduced markedly since they first came onto the market (approximately US$1000 per pill) in 2014, treatment remains unaffordable for many people. In high-income countries with strong public health systems or comprehensive insurance programmes, the price of treatment has been negotiated to a cost that enables the population to access care; however, in many other high-income countries, treatment remains unaffordable, presenting a major barrier to scale-up.3WHOAccelerating access to hepatitis C diagnostics and treatment: overcoming barriers in low- and middle-income countries. WHO, Geneva2021Google Scholar In low-income and middle-income countries (LMICs), voluntary licensing and the Medicine Patent Pool has enabled access to DAAs at less than $60 per treatment course, and, in certain countries, patents for some DAAs have allowed generic manufacturers to set up local production without a license.3WHOAccelerating access to hepatitis C diagnostics and treatment: overcoming barriers in low- and middle-income countries. WHO, Geneva2021Google Scholar However, as highlighted by Isabelle Andrieux-Meyer and colleagues4Andrieux-Meyer I Tan S-S Thanprasertsuk S et al.Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.Lancet Gastroenterol Hepatol. 2021; (published online April 15.)https://doi.org/10.1016/S2468-1253(21)00031-5Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar in The Lancet Gastroenterology & Hepatology, nearly 50 middle-income countries, estimated to have 43% of the global hepatitis C burden, have been excluded from the license agreements of originator companies for key DAAs, making treatment unaffordable for most of their citizens. In an effort to address this crucial issue of treatment affordability, Andrieux-Meyer and colleagues4Andrieux-Meyer I Tan S-S Thanprasertsuk S et al.Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.Lancet Gastroenterol Hepatol. 2021; (published online April 15.)https://doi.org/10.1016/S2468-1253(21)00031-5Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar studied the efficacy and safety of ravidasvir plus sofosbuvir in people with chronic hepatitis C. Ravidasvir is a non-structural protein 5A inhibitor supported by the Drugs for Neglected Diseases initiative in the hope of providing an affordable pangenotypic regimen when used in combination with sofosbuvir. STORM-C-1 is the first part of an open-label, single-arm clinical trial with 301 participants in Malaysia and Thailand (98 [33%] with genotype 1a, 27 [9%] with genotype 1b, two [1%] with genotype 2, 158 [52%] with genotype 3, and 16 [5%] with genotype 6), of whom 81 (27%) had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had previous interferon-based treatment. Key findings in this interim analysis were an overall sustained virological response at 12 weeks after treatment (SVR12) of 97%, an SVR12 of 97% in participants with genotype 3 (a subgroup of patients who have lower SVR12 with some regimens), and an SVR of 96% for participants with cirrhosis. SVR12 rates were unaffected by HIV co-infection or previous interferon treatment history.4Andrieux-Meyer I Tan S-S Thanprasertsuk S et al.Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.Lancet Gastroenterol Hepatol. 2021; (published online April 15.)https://doi.org/10.1016/S2468-1253(21)00031-5Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar The outcomes of STORM-C-1 are encouraging. ravidasvir appears to be an affordable option that could help reduce treatment costs, particularly in middle-income countries that are stuck in the middle—ineligible for the licensed generic drugs but unable to afford current pangenotypic regimens.5Schröeder SE Pedrana A Scott N et al.Innovative strategies for the elimination of viral hepatitis at a national level: a country case series.Liver Int. 2019; 39: 1818-1836Crossref PubMed Scopus (29) Google Scholar However, STORM-C-1 had some limitations. It excluded participants who reported current injecting drug use and hepatitis B co-infection; additionally, SVR12 was lower in those with genotype 6, and no participants had genotype 4. Of note, in a previous study from Egypt examining the efficacy of ravidasvir and sofosbuvir with or without ribavirin, participants with genotype 4 HCV infection had high SVR12 rates.6Esmat G Elbaz T El Raziky M et al.Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4.J Hepatol. 2018; 68: 53-62Summary Full Text Full Text PDF Scopus (14) Google Scholar Although the cost of DAA treatment is important, achieving the WHO 2030 elimination targets requires more than affordable treatment. The availability and affordability of diagnostics remains a major barrier to treatment scale-up, particularly in LMICs. In 2020, prices were $1–8 per test for WHO-prequalified HCV antibody rapid diagnostic tests, but many countries cannot purchase rapid diagnostic tests so cheaply.3WHOAccelerating access to hepatitis C diagnostics and treatment: overcoming barriers in low- and middle-income countries. WHO, Geneva2021Google Scholar Moreover, many health systems require restructuring to meet the needs of individuals who require care; this includes moving care into community settings, supporting task-shifting to reduce reliance on doctors and other highly qualified but few in number medical personnel, and reducing numbers of clinic visits through simplified testing, including point-of-care testing.7Pedrana A Howell J Scott N et al.Global hepatitis C elimination: an investment framework.Lancet Gastroenterol Hepatol. 2020; 5: 927-939Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar Finite resources mean countries must make difficult choices as they work to achieve universal health coverage, a target for 2030 in the UN Sustainable Development Goals.8The WHO Consultative Group on Equity and Universal Health CoverageMaking fair choices on the path to universal health coverage. Final report of the WHO Consultative Group on Equity and Universal Health Coverage. WHO, Geneva2014Google Scholar Countries are advised to identify which interventions to prioritise in their national health benefits package. In making decisions about the composition of health benefits packages, WHO recommends prioritising interventions using three criteria: cost-effectiveness, priority to the worst off, and financial risk protection.9Scott N Kuschel C Pedrana A et al.A model of the economic benefits of global hepatitis C elimination: an investment case.Lancet Gastroenterol Hepatol. 2020; 5: 940-947Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar Lowering the cost of treatment through the availability of drugs, such as ravidasvir, is important to improve cost-effectiveness. However, it also requires political commitment to negotiate and address regulatory and intellectual property barriers. An example of such an approach is in Malaysia, where there has been strong political commitment to support public health programmes and to make HCV treatment available and affordable for the population. Pharco (Alexandria, Egypt) has committed to making the ravidasvir and sofosbuvir combination, once approved, available at a price of $300 or less per treatment course,10Drugs for Neglected Diseases InitiativeDrugs for Neglected Diseases Initiative and Pharco pharmaceuticals to test affordable hepatitis C regimen with support of Malaysian and Thai governments.https://dndi.org/press-releases/2016/dndi-pharco-hepc-malaysia-thailand/Date: 2016Date accessed: April 13, 2021Google Scholar representing a hundredth the cost of the existing originator DAA regimen. Countries also need high-quality surveillance data to identify which health interventions to prioritise and include in their health benefits package. Absent in many countries, high-quality data about hepatitis C is crucial to enable countries to measure and understand the financial risk associated with the direct and indirect costs of hepatitis C morbidity and mortality. Doing nothing has real but often unrecognised costs. The paucity of data, combined with concern about costs, could prevent many countries from meeting the 2030 hepatitis C elimination targets, despite the demonstrable economic benefits of doing so.9Scott N Kuschel C Pedrana A et al.A model of the economic benefits of global hepatitis C elimination: an investment case.Lancet Gastroenterol Hepatol. 2020; 5: 940-947Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar MH and AP leads research that receives investigator-initiated research funding from Gilead Sciences, AbbVie, and Merck Sharp & Dohme. AP reports travel honoraria and consultancy fees from Gilead Sciences outside the submitted work. BD declares no competing interests. Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trialIn this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. Full-Text PDF Open Access