Comment
Hepatitis C drug affordability
www.thelancet.com/lancetgh Vol 3 February 2015
company, to reach a special price of $900 for 12 weeks of treatment in government clinics, but treating 5 million patients of an estimated 11 million infected people will still cost Egypt $4·5 billion of the $7·22 billion total health budget for 2014–15.8 The unprecedentedly high prices being charged for new hepatitis C drugs mean that few patients can benefit and no national population-wide public health benefit can be planned for in affected countries; yet a study by Liverpool University showed that the cost to manufacture a 12-week course of sofosbuvir can be as low as $100–250.4 A
Effect of introduction of generics on prices of ARVs and number of patients
300
Nevirapine Zidovudine/lamivudine Stavudine Zidovudine Lamivudine Didanosine
Number of patients
250
200
150
100
50
Oct, 2000: Importation of generics starts
0
May, 2000
Aug, 2000
Nov, 2000
Feb, 2001
May, 2001
Aug, 2001
Nov, 2001
Feb, 2002
2001
2002
Month/Year
B
Number of patients accessing ARVs at JCRC
4000 3500 3000 Number of patients
The new generation of highly effective medicines to treat hepatitis C offers new hope for those affected, but the high prices of these drugs block countries from integrating them into their treatment programmes. The same obstacle was present at the outset of the HIV/AIDS crisis until the entry of generic companies removed the price obstacle. WHO estimates that 135–150 million people are chronically infected with hepatitis C,1 80% of whom live in middle-income and low-income countries.2 A third of people with chronic infections will develop liver cirrhosis or liver cancer.3 The mortality rate due to hepatitis C is estimated to be 350 000 to 500 000 deaths per year. The disease prevalence is highest in east Asia, the Middle East, and north Africa. The following countries have a hepatitis C prevalence of more than 10%: Egypt (14%), Cameroon (13·8%4), Burundi (11·3%), and Mongolia (10·7%5). Hepatitis C is a curable disease. Not only can patients live without symptoms after successful treatment but their risk of developing hepatocellular carcinoma is also reduced by 75%.6 The new generation of direct-acting antiviral treatments, including sofosbuvir, semiprevir, ledipasvir, and daclatasvir, have a high cure rate of well over 90% and are effective against the difficult-to-treat genotypes. They have better safety profiles, minimum drug interactions, and treatment courses of shorter duration. One great advantage is that these drugs are orally administered. Drug combinations (sofosbuvir with ledipasvir or daclatasvir) achieve higher cure rates even for patients with cirrhosis. However, these medicines are beyond the means of millions of patients. Even in the USA, a heated debate has occurred about the high price of sofosbuvir (US$85 000– 110 000). Some insurance companies have decided to ration the medicine for specific patients. Concerns have also been raised about the extra burden to the public system (Medicaid and Medicare). In Europe, concerns regarding price led 13 European countries to collectively negotiate prices. The French health minister warned that such high prices would impose an unacceptable burden on the social security system, affecting all users.7 Clearly, these prices are not affordable in developing countries. Some governments have begun to negotiate lower prices. Egypt declined to grant a patent for sofosbuvir and negotiated with Gilead, the producing
2500 2000 1500 1000 500 0 1996
1997
1998
1999
2000
Year
Figure: Effect of generic competition on price reduction and numbers of patients accessing ARVs in Uganda Reproduced from an Oxfam Briefing Paper on generic competition, price and access to medicines,11 by permission of Oxfam. ARV=antiretroviral. JCRC=Joint Clinical Research Centre (the largest provider of ARVs in Uganda).
e73
Comment
Several mechanisms have been used to lower the prices of HIV medicines, with varying degrees of success. Tiered pricing—ie, a system by which countries are divided according to their national income and a price is decided for each country tier—is favoured by pharmaceutical companies because it retains their control of prices. This mechanism ignores the fact that most of the world’s poor people live in middle-income countries where tiered prices are unaffordable.9 Another mechanism is voluntary licensing, whereby the patent-holder licences the medicines to one or more generic companies; however, voluntary licences are not transparent and usually come with conditions that might limit production or price reduction. In September, 2014, Gilead issued voluntary licences to seven Indian generic companies to produce sofosbuvir and market it in 91 countries. Although this licence should induce generic competition and thus promise to decrease the price, there are limitations of its use. For example, the licence excludes key countries such as China and Brazil. The Medicines Patent Pool is an independent foundation to which companies surrender their intellectual property rights voluntarily; the foundation then issues sublicenses to generic companies to compete in the production of low-priced medicines in return for a royalty payment. This mechanism has negotiated transparent licenses that are better than individual companies’ licences. Compulsory licensing is a legal instrument that allows governments to break a patent and allows generic companies to produce and market a medicine at an affordable price, paying royalties to the originator companies. This mechanism has been used by Thailand and Brazil for antiretroviral medicines. Other Trade Related Aspects on Intellectual Property Right (TRIPS) flexibilities include pre-grant opposition used by Indian and recently by Argentinean public health advocates to stop patents of medicines.10 Generic competition allows price competition through the entry of several manufacturers when patents are not granted, have expired, or have been voluntarily or compulsorily relinquished. In 2001, the introduction of generic medicines reduced the price of triple antiretroviral therapy from $12 002 to less than $100 per patient per year, which enabled 10 million people to receive antiretroviral treatment (figure).12 The first generation of antiretrovirals was e74
manufactured mainly by Indian companies because India had not at that time implemented the TRIPS. However, generic competition is at risk because most countries have implemented TRIPS and are entering into free-trade agreements that make it difficult to use TRIPS flexibilities, such as compulsory licensing. Learning from the situation with HIV, sustained affordable medicines for hepatitis C cannot be achieved without generic competition. Countries can legally use TRIPS flexibilities, such as compulsory licensing, to enable generic competition. Other mechanisms such as tiered pricing and voluntary licensing must allow generic competition without conditions. Mohga Kamal-Yanni Oxfam, Oxford OX42 JY, UK
[email protected] The article was researched and written as part of my normal work for Oxfam. I declare no competing interests. Copyright © Kamal-Yanni. Open access article published under the terms of CC BY-NC-SA. 1 2 3
4
5 6
7
8
9
10
11
12
WHO. Hepatitis C Fact sheet No 164. April, 2014. http://www.who.int/ mediacentre/factsheets/fs164/en/ (accessed July 16, 2014). Jayasekera CR, Barry M, Roberts LR, Nguyen MH. Treating hepatitis C in lower-income countries. N Engl J Med 2014; 370: 1869–71. WHO. Guidelines for the screening, care and treatment of persons with hepatitis C infection. 2014. http://www.who.int/hiv/pub/hepatitis/ hepatitis-c-guidelines/en/ (accessed July 20, 2014). Hill A, Khoo S, Fortunak J, Simmons B, Ford N. Minimum costs for producing hepatitis C direct-acting antivirals for use in large-scale treatment access programs in developing countries. Clin Infect Dis 2014; 58: 928–36 Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011; 17: 107–15. Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013; 158: 329–37. Agence France-Presse. EU nations join forces against ‘exorbitant’ hepatitis C drug. July 10, 2014. http://news.yahoo.com/eu-nations-join-forcesagainst-exorbitant-hepatitis-c-193456820.html (accessed July 18, 2014). Aggour S. FY 2014/2015 state budget announced, analysts weigh in Daily News Egypt. May 26, 2014. http://www.dailynewsegypt.com/2014/05/26/ fy-20142015-state-budget-announced-analysts-weight/ (accessed July 19, 2014). Moon S, Jambert E, Childs M, von Schoen-Angerer T. A win-win solution?: A critical analysis of tiered pricing to improve access to medicines in developing countries. Global Health 2011, 7: 39. Patent Opposition Database. Argentinian community of people living with HIV file pre-grant opposition against Gilead and BMS’s “ATRIPLA” patent. Dec 4, 2013. http://news.patentoppositions.org/post/70182816078/ argentinian-community-of-people-living-with-hiv (accessed July 18, 2014). Oxfam. Generic competition, price and access to medicines: the case of antiretrovirals in Uganda. Oxfam Briefing Paper 26. http://policy-practice. oxfam.org.uk/publications/generic-competition-price-and-access-tomedicines-the-case-of-antiretrovirals-i-114502 (accessed Dec 29, 2014). WHO, UNICEF, UNAIDS. Global update on HIV treatment 2013: results, imapcts and opportunities. June, 2013. http://www.unaids.org/en/media/ unaids/contentassets/documents/unaidspublication/2013/20130630_ treatment_report_en.pdf (accessed July 17, 2014).
www.thelancet.com/lancetgh Vol 3 February 2015
