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Accelerating access to hepatitis C diagnostics and treatment: Overcoming barriers in low- and middle-income countries - Global progress report 2020

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The 2020 global report on access to hepatitis C diagnostics and treatment is being published at an unprecedented time for global health. The data presented in this report were collected in 2019. Since then, the coronavirus disease (COVID)-19 pandemic has spread to countries and populations worldwide, resulting in 79 million infections and about 1.7 million deaths by end December 2020. Many countries are already facing major disruptions to essential health services. They risk a reversal of decades of progress in health and development. The pandemic is a strong reminder that we need to continue to invest in building resilient health systems for universal health coverage and respond to emergencies. It is also an urgent call to maintain the momentum towards achieving the goals of the 2030 Agenda for Sustainable Development.

This is the third World Health Organization (WHO) global report on access to hepatitis C treatment, following the reports in 2016 and 2018. For the first time, the 2020 report also includes information on hepatitis C diagnostics. The report focuses on 12 countries that represent a combination of high disease burdens and successful public health approaches. It provides updates on the diverse landscape of national strategies and market conditions, which together shape a country’s response to viral hepatitis. The report demonstrates how programmes in different settings are achieving greater affordability, quality, equity and efficiency in scaling up hepatitis C diagnostics and treatment. The practical lessons and examples illustrate how all countries can further simplify, decentralize and expand service delivery to achieve universal coverage.

The global response to hepatitis C is positioned for “take-off” for a decade of acceleration towards the goals of the 2030 Agenda for Sustainable Development. Following the adoption of the first Global Health Sector Strategy on Viral Hepatitis 2016–2021, a number of countries have made impressive gains supported by government commitment, national strategic plans, simplified guidelines, greater availability of quality-assured diagnostics and treatment options, and continued price reductions. While less than 20 countries had national viral hepatitis strategic plans in 2012, this had increased to 124 countries by 2018. In the 12 countries highlighted in this report, eight have comparable yearly data on access to hepatitis C treatment. The data showed that the cumulative number of people receiving hepatitis C treatment grew more than 20-fold between 2015 and 2018 – from about 122 000 patients at the end of 2015 to more than 2.6 million by the end of 2018.

Some champion countries are leading the way and have contributed massively to the recent scale up. Egypt, one of the countries with the largest burden of hepatitis C infection in the world, has made significant advances since 2018 towards hepatitis C elimination through a large countrywide public health effort to screen the entire population aged 18 years and older (a target population of 62.5 million) and link those in need to care. Nearly 50 million adults and 9 million children aged 12–18 years were screened, and 1.5 million additional persons had started treatment by mid-2019. This constitutes one of the largest public health efforts to date towards hepatitis C elimination in low- and middle-income countries. Egypt now plans to support other countries in the sub-Saharan African region in their scale up efforts. Other countries such as Georgia, Mongolia, Pakistan and Rwanda have also greatly expanded their outreach in the past couple of years. The common factors for the success of the public health response in these countries include strong political commitment, widespread testing, and a comprehensive strategy to deliver services through an integrated approach within the framework of universal health coverage. Countries have leveraged existing health infrastructure and the experience of programmes such as HIV to expand hepatitis screening and testing services, and seized opportunities to address patent- and regulation-related challenges specific to the country context. They have also leveraged domestic financing, generic competition and pricing reduction, and worked alongside civil society to advocate for reduced prices and support access for those most at risk and vulnerable. Important lessons can be learned from the experiences of these countries.

The WHO 2017 guidelines on hepatitis B and C testing, and the WHO 2018 guidelines for the screening, care and treatment of persons with chronic HCV infection provide a timely opportunity to accelerate access. These guidelines introduced major simplifications in the delivery of testing (screening and diagnosis) and treatment services within a public health approach. The goal of hepatitis C treatment is cure. The guidelines included a simplified two-step testing strategy to diagnose chronic hepatitis C virus (HCV) infection. A “treat all” approach with prompt treatment initiation is taken for all people living with chronic HCV infection – defined as those with active viraemic infection (with the exception of pregnant women and children under 12 years) – with direct-acting antiviral (DAA) drugs that can cure more than 95% of cases with chronic HCV, thereby reducing the risk of death from cirrhosis or liver cancer. The guidelines recommend the use of three pangenotypic regimens, which can treat all strains of HCV without the need for additional specialized genotyping, and WHO is supporting countries to transition to these new regimens. In addition, the updated guidelines also provide key good practice approaches to support simplified service delivery across the continuum of care.

The sources of quality-assured generic direct-acting antivirals and diagnostics are steadily increasing. In 2016, there were no generic DAAs that were WHO-prequalified or approved by a stringent regulatory authority. By 2020, six generic manufacturers had at least one DAA prequalified by WHO. By the end of 2020, a WHO-prequalified fixed-dose combination of sofosbuvir/daclatasvir was available from a generic supplier. In-country product registrations are also increasing. In 2019, a total of 62 low- and middle-income countries had registered at least one version of sofosbuvir and daclatasvir, sofosbuvir/ledipasvir or sofosbuvir/velpatasvir from the originator or generic manufacturers, as compared to 32 in 2017. Similarly, only one HCV rapid diagnostic test and a line immunoassay were prequalified in 2016. By 2020, four molecular HCV assays and eight serology assays were WHO-prequalified.

Prices of DAAs continue to fall, supported by increased generic competition. Low- and middle-income countries can now aim to achieve a price as low as US$ 60 per patient for a 12-week course of treatment with WHO-prequalified generic sofosbuvir and daclatasvir, one of the lowest reported prices for WHO-prequalified generic hepatitis C medicines to date. Between 2016 and 2018, the lowest reported price per 28-day supply of sofosbuvir dropped by 75% from US$ 60 to US$ 15, and for daclatasvir by 60% from US$ 15 to US$ 6; both reported from India for the domestic market for WHO-prequalified products.

Prices have also dropped for the generic fixed-dose combination of sofosbuvir/daclatasvir, which has become the pangenotypic regimen of choice for most countries, given its favourable pricing and the availability of several pre-qualified products. A WHO-prequalified generic fixed-dose combination of sofosbuvir/daclatasvir was available in India for US$ 23 per 28-day supply or US$ 69 per course of treatment. Some generic manufacturers who are not yet WHO-prequalified are reporting even lower prices. Generic sofosbuvir/daclatasvir was available for US$ 16 per 28-day supply or US$ 48 per course of treatment from a local manufacturer in Egypt and for US$ 7–10 per 28-day supply or US$ 25 per course of treatment from a local manufacturer in Pakistan. However, many countries are not benefiting from these prices, and large variations in prices and patent barriers continue to persist among countries. Prices in upper-middle-income countries remain a major barrier to scale up.

The availability and affordability of diagnostics remains a major barrier to treatment scale up, in particular, in low- and middle-income countries. Information on the pricing of HCV in vitro diagnostics (IVDs) is limited, and the market is dominated by a small number of companies. In 2020, prices offered by suppliers of WHO-prequalified HCV rapid diagnostic tests ranged between US$ 1 and US$ 8 per test, yet many countries are not accessing rapid diagnostic tests at these low prices.

Laboratory-based immunoassays were offered at a price between US$ 1 and US$ 2. Reagents for nucleic acid testing (NAT) that can be used at the point of care (POC) to detect HCV RNA cost between US$ 14 and US$ 30, plus the fixed costs of the analyser itself, which ranges from US$ 10 000 to US$ 25 000. High-throughput laboratory-based analysers can cost over US$ 100 000, with reagents costing between US$ 9 and US$ 50 per test. Manufacturers of diagnostic platforms/analysers are offering various pricing schemes, such as reagent rental and leasing agreements. However, many low- and middle-income countries with nascent screening programmes and low testing volumes have not been able to fully benefit from these schemes and leverage existing infrastructure. As hepatitis C treatment becomes more affordable and widely available, expanding access to simple, affordable and quality-assured hepatitis C IVDs is much needed so that countries can screen large numbers of people, identify patients in need of treatment and provide appropriate care.

Efforts to address patent-related barriers are making products more accessible but there are still obstacles to be overcome. In a major step towards expanding access to glecaprevir/pibrentasvir, a voluntary license agreement was signed at the end of 2018 between the originator company AbbVie and the Medicines Patent Pool (MPP). This enables generic manufacturer partners in low- and middle-income countries and areas to develop and supply a quality-assured pangenotypic combination, making this drug regimen more accessible. However, many upper-middle-income countries are not included in this agreement, and neither is India. AbbVie has signed a licensing agreement with one generic manufacturer; however, generic production of glecaprevir/pibrentasvir had not yet started as of mid-2020. For daclatasvir, BMS announced in early 2020 that the marketing authorizations for its originator product will be withdrawn or will be allowed to lapse in countries where the product is no longer routinely prescribed or where there are other therapeutic options available. Following the withdrawal/ lapse of the marketing authorization, the patents in those countries will also be allowed to lapse and will not be enforced in the interim period. This decision has an important impact on access to daclatasvir, with 26 additional countries, including some outside the licensed territory to the MPP, now having access to generic daclatasvir, with or without existing patents. For sofosbuvir, ledipasvir and velpatasvir, the number of countries included in the voluntary licensing agreement of Gilead has remained unchanged, and many high-burden countries remain excluded. For diagnostics, the role of patent protection is often more complex than it is for medicines, because many different constituents of IVDs and the technique may be patented.

Despite recent achievements in many areas, the overall global landscape of access to hepatitis C diagnostics and treatment remains uneven and fragmented. The progress achieved to date is fragile, and access to hepatitis C testing and treatment is yet to reach sufficient levels of coverage to attain the global goal of eliminating viral hepatitis as a major public health threat by 2030. Globally, at the end of 2017, only 5 million – or 7% – of the 71 (62–79) million people chronically infected with HCV had cumulatively received treatment with DAAs. Access to hepatitis C diagnosis and treatment remains low in many low- and middle-income countries with a high disease burden, and not all countries have been able to equally avail of opportunities to address barriers related to pricing, patents, product regulation and demand creation. The COVID-19 pandemic may not only slow down progress but may also reverse the gains.

Importantly, the population groups that are most at risk of hepatitis C infection continue to be underserved in access to services, and data on coverage in these groups are lacking. A WHO desk review in 2019 of 81 national hepatitis policies and plans found that less than half of them outlined the necessary harm reduction and hepatitis C testing and treatment interventions for people who inject drugs, in accordance with the Global Health Sector Strategy on Viral Hepatitis. Global targets will not be met without massively accelerating universal access to hepatitis C testing, treatment and prevention services for people who inject drugs, people in prisons, men who have sex with men, and other vulnerable groups; and leveraging synergies with related services such as those for HIV prevention, treatment and care, and substance use.

As countries continue to tackle the disease burden and service disruptions caused by the COVID-19 pandemic, it is critical to ensure that the recent momentum and gains in the response to hepatitis C are not lost. Global efforts to scale up access to high-impact interventions for hepatitis C through a public health approach must be sustained and accelerated in the coming decade, as part of broader efforts towards universal health coverage.

The key priorities include:

  • accelerating universal access to hepatitis C IVDs that can be used at or near the POC for all through decentralization of screening and diagnostic services, task-sharing, simplifications in sample transportation and service delivery, integration with existing infrastructure, leveraging multi-disease diagnostic platforms, obtaining more favourable prices, pooling procurement across diseases and fostering demand creation;

  • continuing to pursue comprehensive strategies for more affordable hepatitis C diagnostics and treatment across all country income categories; including through addressing patent-related barriers and public health-oriented licensing, and generic manufacturing of quality-assured medicines. Other strategies are price– volume negotiations with manufacturers to create high volume, low costs and high-value markets, including value-for-money reagent rental agreements for HCV NAT platforms. Access should be promoted through market intelligence and greater market transparency, patent oppositions, generic competition and leveraging efficient procurement processes;

  • leaving no one behind in line with the SDGs, by ensuring universal health coverage inclusive of key, underserved and overlooked populations, such as people who inject drugs, people in prisons, migrant and refugee populations, men who have sex with men, people living with HIV with comorbidities and other vulnerable groups; investing in data and targets that account for progress in these groups; and engaging communities in planning and decision-making;

  • facilitating product registration of quality-assured recommended DAAs with national regulatory authorities through approaches such as leveraging the WHO Collaborative Procedure for Accelerated Registration, or using drug waivers – supported by documentation related to WHO prequalification – to expedite access while in the process of obtaining full registration. This would ensure rapid in-country availability of diagnostic and treatment commodities, increase competition, lower prices and minimize service disruptions;

  • seeking greater financing options, in particular, by leveraging domestic financing as part of integrated public health approaches and universal health coverage packages in low- and middle-income countries with varying disease burdens. Opportunities provided by existing international funding mechanisms such as The Global Fund should also be built on for synergistic interventions;

  • leveraging synergies across the health sector, such as through the use of multi-disease diagnostic platforms/analysers (including NAT platforms for use at POC), common service delivery platforms (e.g. harm reduction for HIV and viral hepatitis), facilitating integration of hepatitis commodities into existing national procurement and supply mechanisms of essential medicines, and using common approaches to strengthening person-centred data systems and human resources for health.