Antiviral treatment for hepatitis C: rebalancing cost, affordability, and availability
Authors: Geoffrey Dusheiko, Charles Gore
Journal: The Lancet Global Health (2019)

Direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) rank among the most significant biopharmaceutical advances in medicine. The worldwide threat of the disease and the advent of near-universal cures for chronic HCV infection have driven advocacy for treatment as control and led to the specification of elimination targets. However, use of treatment as a control measure would necessitate widespread testing for HCV as well as access to antiviral drugs, thus provoking immediate debates over cost, profit, and affordable access. DAA regimens were initially high-cost treatments. However, the market has done its work for HCV treatments: after competing antiviral regimens entered the market, competition and innovative price negotiations have driven costs down from the initially high list prices in developed countries.1Moon S Erickson E Universal medicine access through lump-sum remuneration—Australia's approach to hepatitis C.N Engl J Med. 2019; 380: 607-610Crossref PubMed Scopus (25) Google Scholar, 2Villa F Tutone M Altamura G et al.Determinants of price negotiations for new drugs. The experience of the Italian Medicines Agency.Health Policy. 2019; 123: 595-600Crossref PubMed Scopus (10) Google Scholar Previously, low-income and middle-income countries (LMICs) depended on generic competitors entering the market at the end of a drug's lifespan, but voluntary licensing has changed this system. A voluntary licence is an agreement that allows others to manufacture, import, and distribute a patent holder's patented drug. Licences can also be negotiated via patent pooling mechanisms, such as the Medicines Patent Pool, which licenses rights to manufacture treatments to generic pharmaceutical companies. These mechanisms allow lower-cost generics to reach the market in a timely manner by allowing generic manufacturers to exploit the original innovation and—through manufacturing expertise and by obviating research and development expenditure—substantially reduce prices. HIV treatment provided the exemplar that enabled widespread affordable treatment, improving access in emerging economies.3Juneja S Gupta A Moon S Resch S Projected savings through public health voluntary licences of HIV drugs negotiated by the Medicines Patent Pool (MPP).PLoS One. 2017; 12e0177770Crossref PubMed Scopus (8) Google Scholar In The Lancet Global Health, Bryony Simmons and colleagues4Simmons B Cooke G Miraldo M Effect of voluntary licences for hepatitis C medicines on access to treatment: a difference-in-differences analysis.Lancet Glob Health. 2019; (published online July 27.)http://dx.doi.org/10.1016/S2214-109X(19)30266-9Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar examine to what extent voluntary licensing might have improved treatment uptake for HCV infection in LMICs since 2014. The authors used annual data on the proportion of people accessing treatment from 2004–16, comparing trends before and after the introduction of voluntary licensing in recipient countries to evaluate a possible causal effect on treatment access. The statistical analysis was done by use of a difference-in-differences method to measure the effect of the intervention in a group of LMICs. The average annual treatment uptake, measured as the number treatment courses administered per 1000 living people ever diagnosed with HCV, increased substantially after the introduction of voluntary licences in 2014, suggesting that this licensing has led to price reductions and consequent increases in treatment access, beyond that expected in the absence of licensing, in the LMICs studied. In this analysis, at baseline (2013), there was considerable variation across countries in the proportions of people accessing treatment. As might be expected, the licensed countries had lower gross domestic product per capita. Over the study period, two companies introduced active licences for DAAs for HCV: Gilead introduced licences first for sofosbuvir and later for the newer compounds ledipasvir, velpatasvir, and voxilaprevir, including 91 countries (predominantly LMICs) in these agreements; and Bristol-Myers Squibb introduced a licence for daclatasvir via the Medicines Patent Pool to cover 112 LMICs. The evidence base and data sources (derived from surveillance databases, national registries, and drug suppliers' data) contain potential confounders. First, these were secondary estimates, and the data do not fully triangulate the evidence from these multiple sources. In addition, the authors selected a small subset of countries from which to pool the data, and the attributes of socioeconomic factors and programmatic infrastructure in the target countries are unclear. Factors that could have influenced screening, linkage to care, and treatment uptake (including the increased demand for the safer and highly efficacious oral DAA therapies to replace injectable interferon treatment) were also not elaborated. Finally, the analysis did not disentangle how generic drugs were procured in the studied countries (ie, whether the uptake in DAA treatment was accounted for mainly by increases in government spending or by private prescriptions by high-income groups within LMICs).5Ongarora D Karumbi J Minnaard W Abuga K Okungu V Kibwage I Medicine prices, availability, and affordability in private health facilities in low-income settlements in Nairobi County, Kenya.Pharmacy (Basel). 2019; 7: E40Crossref PubMed Google Scholar Nevertheless, the data support the inference that voluntary licensing has been beneficial for treatment access. Robust generic competition and the Medicines Patent Pool provide a platform for more affordable spending on DAA, which should incentivise and encourage case finding.6Cooke GS Andrieux-Meyer I Applegate TL et al.Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission.Lancet Gastroenterol Hepatol. 2019; 4: 135-184Summary Full Text Full Text PDF PubMed Scopus (166) Google Scholar Licensing agreements and the procurement of generic drugs have facilitated the roll-out of treatment for HIV and AIDS, and could also lead to progress for HCV. Access to HCV treatments remains circumscribed, perhaps partly because only 20% of the estimated 70 million people with HCV know their diagnosis, and probably less than 4 million have been treated.7WHOClose to 3 million people access hepatitis C cure.https://www.who.int/news-room/detail/31-10-2017-close-to-3-million-people-access-hepatitis-c-cureDate: Oct 31, 2017Date accessed: July 7, 2019Google Scholar The incentive of affordable treatments has overcome reservations regarding increased testing and treatment of HCV in many countries; more LMICs can be persuaded to develop national plans for integrated upscaled programmes for HCV testing and mass drug administration, to reach millions of people per year, without incurring ruinous and unrealistic health expenditures.8Andrieux-Meyer I Cohn J de Araújo ES Hamid SS Disparity in market prices for hepatitis C virus direct-acting drugs.Lancet Glob Health. 2015; 3: e676-e677Summary Full Text Full Text PDF PubMed Scopus (60) Google Scholar Control of HCV infection will now hinge on crucial advances in affordable point-of-care testing. Voluntary agreements have allowed originator manufacturers to enter developing markets, and achieve social responsibility, measurable by trackers such as the Access to Medicine Index.9Hogerzeil HV Big Pharma and social responsibility—the Access to Medicine Index.N Engl J Med. 2013; 369: 896-899Crossref PubMed Scopus (18) Google Scholar In November, 2018, the Medicines Patent Pool signed a licence agreement with AbbVie for glecaprevir and pibrentasvir, enabling sales of these drugs to 96 LMICs.10Medicines Patent PoolLicense agreement (AbbVie—glecaprevir/pibrentasvir).https://medicinespatentpool.org/uploads/2018/11/AbbVie-MPP-Executed-HCV-Agreement.pdfDate accessed: July 7, 2019Google Scholar Simmons and colleagues' paper highlights what can be done to bring medicines to an expansive list of LMICs to expedite the control of HCV infection. The next question is how well this model can, by extension, be applied to other essential medicines in line with WHO's Roadmap for Access, to improve the availability and affordability of health products.11Beck EJ Mandalia S DongmoNguimfack B et al.Does the political will exist to bring quality-assured and affordable drugs to low- and middle-income countries?.Glob Health Action. 2019; 121586317Crossref PubMed Scopus (4) Google Scholar GD reports grants and personal fees from Gilead Sciences (donated to UNICEF) and grants from Merck, during the conduct of this work. CG declares no competing interests. Effect of voluntary licences for hepatitis C medicines on access to treatment: a difference-in-differences analysisVoluntary licensing initiatives appear to substantially improve HCV treatment uptake in eligible countries. This evidence supports the expansion of licensing strategies to include more countries and more treatments. Full-Text PDF Open Access