Policy & practice

Access to medicines Danny J Edwards,a Delphi GM Coppens,a Tara L Prasad,a Laurien A Rooka & Jayasree K Iyera

Abstract Hepatitis C is a global epidemic. Worldwide, 185 million people are estimated to be infected, most of whom live in low- and middle-income countries. Recent advances in the development of antiviral drugs have produced therapies that are more effective, safer and better tolerated than existing treatments for the disease. These therapies present an opportunity to curb the epidemic, provided that they are affordable, that generic production of these medicines is scaled up and that awareness and screening programmes are strengthened. Pharmaceutical companies have a central role to play. We examined the marketed products, pipelines and access to medicine strategies of 20 of the world’s largest pharmaceutical companies. Six of these companies are developing medicines for hepatitis C: AbbVie, Bristol-Myers Squibb, Gilead, Johnson & Johnson, Merck & Co. and Roche. These companies employ a range of approaches to supporting hepatitis C treatment, including pricing strategies, voluntary licensing, capacity building and drug donations. We give an overview of the engagement of these companies in addressing access to hepatitis C products. We suggest actions companies can take to play a greater role in curbing this epidemic: (i) prioritizing affordability assessments; (ii) developing access strategies early in the product lifecycle; and (iii) licensing to manufacturers of generic medicines.

Introduction However, there are also critical differences between the two epidemics that influence how pharmaceutical companies Hepatitis C is an infectious disease caused by the hepatitis C design access strategies. With HIV, the greatest disease bur- virus (HCV). There is a global epidemic of hepatitis C, with den is situated in lower-income countries and concentrated approximately 185 million people estimated to be infected in in sub-Saharan Africa.7 These countries were not viewed, in 20051 and 350 000–500 000 deaths estimated annually.2 Over the earlier days of the epidemic, as representing market po- 80% of those affected by the disease live in low- and middle- tential. In contrast, HCV is prevalent in some middle-income income countries, especially in central, north and west Af- countries.4 Middle-income countries, though home to most of rica.3,4 Several middle-income countries such as Egypt, Nigeria the world’s poor,8 have growing middle classes,9 representing and Pakistan have a high burden of hepatitis C. economic opportunities for pharmaceutical companies. As a HCV is most often spread when infected blood en- result, companies have an incentive to maintain exclusivity ters the body. High-risk populations include intravenous and charge higher prices in these markets. This may discour- drug-users and recipients of blood transfusions in poorly age donor, insurer and government investment in expensive controlled environments;2 but the virus is also found in the new treatments,10 potentially slowing the adoption of new general population. There are six genotypes of HCV, with medicines. distributions varying by region. It is possible for a person to Here we identify marketed products, product pipelines be infected with multiple genotypes; 55–85% of people will and access to medicine strategies of companies that make develop chronic and about one third of these, if not HCV medicines. We describe companies’ plans and activities treated, will eventually develop liver cirrhosis or hepatocellular to support greater access to HCV treatment and set out the carcinoma.2 Approximately 80% of newly-infected people are criticisms, limitations and opportunities of these approaches. asymptomatic, which makes it difficult to diagnose and treat Finally, we present recommendations for companies to those who go on to develop chronic infection.2 consider when developing access to medicine strategies for Newly-available drugs have revolutionized treatment.5 HCV-infected people. Previous treatments were poorly tolerated and had limited suc- cess. In contrast, the new treatments are easier to administer Hepatitis C medicines with shorter course durations and higher cure rates.5 There are significant similarities between the hepatitis C We used data from the Access to Medicine Index 201411 and epidemic and the human immunodeficiency virus (HIV) crisis other publicly-available sources such as company, patients’ of the late 1990s. Both involve global spread of underdiagnosed organization and nongovernmental organization websites. The disease that can carry significant stigma and cause life-long access to medicine index is created by the Access to Medicine illness and death. In both cases, there are new, effective prod- Foundation, an independent initiative funded by the Bill & ucts that can curb the global epidemic, held back by issues Melinda Gates Foundation, the Dutch Ministry of Foreign of affordability. The HIV crisis in South Africa resulted in a Affairs, the United Kingdom Department for International clash between civil society, government and the pharmaceuti- Development, and the Dutch National Postcode Lottery. The cal industry,6 which led to the development of new ways of Access to Medicine Foundation engages directly with 20 of working, most notably with generic medicine manufacturers the world’s largest pharmaceutical companies, requesting via licensing arrangements, creating a blueprint for access to data biennially on selected activities via a detailed online medicine strategies for years to come. questionnaire.12 The data are used to rank the companies in

a Access to Medicine Foundation, Scheepmakersdijk 5A, 2011 AS, Haarlem, Netherlands. Correspondence to Danny J Edwards (email: [email protected]). (Submitted: 7 May 2015 – Revised version received: 5 August 2015 – Accepted: 8 August 2015 – Published online: 8 October 2015 )

Bull World Health Organ 2015;93:799–805 | doi: http://dx.doi.org/10.2471/BLT.15.157784 799 Policy & practice Hepatitis C medicines Danny J Edwards et al.

Table 1. Currently marketed hepatitis C medicines from pharmaceutical companies, 2015

Company Brand name INN Class Market approval EML FDA EMA AbbVie Viekira Pak® // + Direct acting antiviral 2014 – No (combination) AbbVie Viekirax® ombitasvir/paritaprevir/ritonavir Direct acting antiviral – 2015 Yes AbbVie Exviera® dasabuvir Direct acting antiviral – 2015 Yes Bristol-Myers Daklinza® Direct acting antiviral – 2014 Yes Squibb Gilead Sovaldi® Direct acting antiviral 2013 2014 Yes Gilead Harvoni® sofosbuvir/ Direct acting antiviral 2014 2014 Yes (combination) Johnson & Olysio® Direct acting antiviral 2013 2014 Yes Johnson Johnson & Incivo® Direct acting antiviral 2011a 2011 No Johnson Merck & Co. Victrelis® Direct acting antiviral 2011a 2011 No Merck & Co. PegIntron® peginterferon alfa-2b 2001 2000 Yes Roche Pegasys® peginterferon alfa-2a Interferon 2002 2002 Yes Roche Copegus® Nucleoside analogue 2002 2002 Yes EMA: European Medicines Agency; EML: World Health Organization Essential Medicines List; FDA: US Food and Drug Administration; INN: international nonproprietary name. a Now discontinued in the US market. Note: Only FDA and EMA drug registrations are tracked. a biennial index. This index uses a set countries where treatment is available, agent therapies, are now available on of 95 indicators to assess companies’ all persons diagnosed with chronic HCV the market. They are more effective, comparative performance in facilitating infection are typically considered suit- safer and better-tolerated than existing access to medicines in poor populations. able for treatment. In countries where therapies: 90% of people are cured.14 The A limitation of the data is that they are treatment availability is constrained, therapies are orally administered and largely self-reported by companies. treatment is prioritized for patients in have shorter treatment courses (12–24 However, the data are reviewed by an more advanced stages of the disease. Dif- weeks depending on regimen and external research partner (for the 2014 ferent treatment regimens are advised genotype),1 which decreases monitoring index, this partner was Sustainalytics, depending upon HCV genotype.1 requirements.5 Five currently-marketed Amsterdam, Netherlands) and the foun- Older HCV treatments comprised therapies were added to WHO’s essential dation’s research team, clarified with combination antiviral therapy with pe- medicines list in 2015 (Table 1).15 companies and verified in some areas gylated interferon (weekly injections) Of the 20 companies evaluated in with external data sources. and ribavirin (tablet, capsules, or oral the access to medicines index, six are Current treatment solution). Pegylated interferon, which active in HCV medicine development remains on patent in most countries, (AbbVie, Chicago, USA; Bristol-Myers The World Health Organization (WHO) was added to WHO’s essential medicines Squibb, New York City, USA; Gilead, released new treatment guidelines for list in 2013. Ribavirin is off-patent and Foster City, USA; Johnson & Johnson, hepatitis C infection in April 2014.1 generic versions exist. Two companies New Brunswick, USA, Merck & Co., Given that most patients will not re- (Merck & Co, Kenilworth, United States Roche). All have products on the market alize they are infected, screening is of America (USA) and Roche, Basel, and in development. In the US market recommended for high-risk groups. In Switzerland) included in the access to Merck & Co. and Vertex recently dis- countries with high prevalence and low medicines index manufacture inter- continued boceprevir and telaprevir infection control, screening is recom- feron; one also manufactures ribavirin respectively, with Merck & Co. citing mended for the whole population, if (Roche). This treatment regime is not “advancement in treatment practices”.16 resources allow this.1 However, diagnos- widely available, can be poorly toler- Boehringer Ingelheim (Ingelheim am tic capacity is limited in many low- and ated and has undesirable side-effects. Rhein, Germany) ceased engagement middle-income countries.10 In Egypt, a 48 week course of peginter- in research and development for HCV The size of the population requiring feron/ribavirin costs 2000 United States in June 2014, in view of “multiple drug treatment for hepatitis C is difficult to dollars (US$).1 Only 30–50% of people approvals expected from alternative gauge. As noted, not all of the 185 mil- are cured, partly because many patients manufacturers”.17 lion people estimated to be infected will don’t finish treatment.1,2 One company that is not included progress to chronic infection, and there New treatment options in the access to medicines index (Achil- are no conclusive predictors of disease lion, New Haven, USA) was identified progression.13 There is currently no vac- New antiviral drugs for HCV infection, as active in HCV drug development; cine against HCV.1 In higher-income known as oral directly-acting antiviral Genentech (San Francisco, USA),

800 Bull World Health Organ 2015;93:799–805| doi: http://dx.doi.org/10.2471/BLT.15.157784 Policy & practice Danny J Edwards et al. Hepatitis C medicines

Fig. 1. Clinical trial stage of 32 hepatitis C medicines, 2015

Phase I Phase II Phase III

ABT-450/ritonavir + ABT-267 + ABT-333 (broad GT-1) ABT-450/ritonavir + ABT-267 (asia development) dasabuvir (ABT-333) ombitasvir (ABT-267)

ie paritaprevir (ABT-450)

AbbV ABT-072 ABT-493 ABT-530 ABT-450/ritonavir + ABT-267 (optimized GT-1b/4) ABT-493 + ABT-530 (broad second generation pangenotypic) (NS3 inhibitor) FDC: asunaprevir + daclatasvir + beclabuvir ers Squibb (name not disclosed) (non-nucleoside NS5B) ristol-My y B Anti-PD-L1 FDC: sofosbuvir and GS-5816 (nucleotide NS5B inhibitor/pan-genotypic NS5A inhibitor) ompan C GS-9451 (NS3 inhibitor)

Gilead GS-9669 (non-nucleoside NS5B site 2 polymerase inhibitor) GS-9620 (TLR-7 agonist) FDC: simeprevir + sofosbuvir simeprevir (paediatric) FDC: simeprevir_647055/GSK805

Johnson & telaprevir VX-950 (paediatric)

. FDC: +

ck & Co (MK-7009) Mer

Roche (name not disclosed) (TLR-7)

FDC: fixed-dose combination; GT: genotype; NS3: nonstructural protein 3; NS5A: nonstructural protein 5A; NS5B: nonstructural protein 5B; PD-L1: programmed death-ligand 1; TLR: toll-like receptor. Note: Codes appearing within this table (e.g. ABT-450) are company codes, used to identify the drug while it is in development.

Kadmon and Medivir AB (Stockholm, Access to medicine strategies access strategies identified is provided Sweden) are also involved in marketing in Table 2. HCV products.18 For the 2014 access to medicine index, Disclosure of access to medicine Table 1 and Fig. 1 show, respective- companies were asked to disclose plans strategies for products that were still ly, currently marketed HCV products for making HCV products available in under development was limited across (FDA and EMA registrations only) and low- and middle-income countries. in-house and collaborative projects. an overview of products in research and We refer to these as company access This may reflect intense competition in development, up to date at the time of strategies. Companies shared informa- HCV medicines. Only Gilead disclosed this paper’s submission. Table 1 indi- tion about equitable pricing strategies access strategies for products under cates the presence of several new prod- (which take affordability into account development, having agreed licensing ucts on the market. Fig. 1 summarizes for poor populations), voluntary licens- conditions for two products before the progress in development of HCV ing agreements, donations of products registration. medicines, with many products in phase and capacity-building initiatives. John- Access strategies are in place for two III of clinical trials. Future competition son & Johnson and AbbVie disclosed no newly marketed products: sofosbuvir may play an important role in enhancing access to medicine strategies. Several and ledipasvir (Gilead) and were also affordability, contingent on the relative new HCV products and access strate- in place for boceprevir (Merck & Co, efficacy of competitors and how broadly gies were launched after the period now discontinued). Three companies companies choose to register them. of analysis ended. A summary of the are active in pricing strategies (Gilead,

Bull World Health Organ 2015;93:799–805| doi: http://dx.doi.org/10.2471/BLT.15.157784 801 Policy & practice Hepatitis C medicines Danny J Edwards et al.

Table 2. Access strategies for hepatitis C medicines, 2015 ternational and national funders from allocating funding at the scale required Companya Brand name Pricing Financing Licensing Capacity Donations for the widespread rollout of new HCV buildingb treatments. AbbVie Viekira Pak® No No No No No Generic partners Bristol-Myers Daklinza® C No C Yes No The lessons from scaling up HIV/AIDS Squibb medicines have shown that the capac- Gilead Sovaldi® Yes No Yes No No ity of generic medicine manufacturers to Johnson & Olysio® No No No No No produce high-quality medicines and their Johnson knowledge of local regulatory require- Merck & Co. Pegintron® Yes Yes No Yes No ments are important for manufacture, dis- Roche Pegasys® and Yes No No Yes Yes tribution and treatment. Equally important Copegus® is the impact of sufficient competition from a With marketed product or products. generic medicine manufacturers on prices: b Including philanthropic activity. the average price of a first-line adult antiret- Note: Yes: has a strategy; No: does not have a strategy; C: commitment only roviral regimen dropped from US$ 414 per person per year in 2003 to US$ 74 in 2008.27 Merck & Co. and Roche). Only Gilead is prices for sofosbuvir in the United States Licensing can also make business currently actively licensing HCV prod- are being increasingly discounted in the sense. For example, efficiencies may ucts. In late 2014, Bristol-Myers Squibb face of competition.20 exist in engagement with generic manu- announced an intention to engage in Companies should develop, with facturers who understand local regula- both licensing for HCV products and governments, mechanisms for sig- tory requirements well, have an existing tiered pricing (in which different price nificant price discounting based on network of contacts with developing points are set depending on the market rigorous, well researched, transparent country governments and regulators in which the product is sold).19 assessments of affordability in low- and and can rapidly scale up production. middle-income countries, clearly tak- Manufacturers may derive income from Discussion ing account of the needs and abilities the application of royalties to licence of payers and the presence or absence agreements, for example 7% royalties Ensuring access to medicines is a joint of subsidies. were attached to the licences agreed by responsibility of governments, com- Separate pricing policies within Gilead for sofusbuvir.28 panies, multilateral agencies and non- countries can make sound business To date, Gilead is the only manu- governmental organizations (NGOs). sense and improve access.21 In middle- facturer of new HCV medicines to have Pharmaceutical companies, being pri- income country markets with greater completed agreements with generic vate entities, must also be able to justify economic value to companies, private medicine manufacturers. The number of their access to medicine activities to and public systems can be offered differ- manufacturers12 is, arguably sufficient to shareholders. ent brands and prices. This is known as engender competition and the full agree- We have highlighted two key points market segmentation. Proposed strate- ments have been publicly disclosed.29 of entry for pharmaceutical companies gies from Gilead for enforcing market Although the scope of the licences to help to address access to HCV medi- segmentation of sofosbuvir requiring appears broad, they do not include key cines. First, affordability: the high prices patient identification and limited dis- middle-income country markets with attached to new medicines may be deter- pensing were criticized for risking con- high HCV burdens, such as Brazil, ring donors (international or bilateral), fidentiality and adherence.22 For poorer China, Georgia, Mexico, Thailand and health insurers and governments from populations, high-volume, low-cost ap- Ukraine.30 Further, it is not yet clear on committing sufficient funds to curbing proaches may prove more profitable: in what scale generic manufacturers will the epidemic.10 Where drugs are paid for the United States, Gilead appears to be enter the market, nor what discounts out-of-pocket, ensuring affordability is shifting to a higher-volume/lower-price will be realized, though NATCO, Hy- also critical. Second, generic manufac- model as competition from AbbVie derabad, India, has disclosed a price of turers can scale up and distribute new intensifies.23 19 900 Indian rupees for 28 400 mg tab- medicines. Generating sufficient com- Gilead initially charged US$ 84 000 lets in Nepal.31 On a 12-week course of petition among generic manufacturers for a course of sofosbuvir in the United treatment, this equates to approximately will place downward pressure on prices. States. The lowest identified price for US$ 900. So, although Gilead’s licens- Affordability that treatment in a developing country ing activities represent leading practice was US$ 900 in Egypt.24 These prices are among the companies included in the Manufacturers of new HCV medicines much higher than the drug’s production access to medicine index, this approach will benefit from market exclusivity cost, which is US$ 68 to US$ 136 for has limitations in geographic scope until around 2025.10 For Gilead, this a 12-week course.25 We were not able and improvements in affordability are monopoly has been magnified by the to estimate the research and develop- not yet clear. Bristol-Myers Squibb has dominance of sofosbuvir. However, this ment costs for this drug, and Gilead also announced its intention to engage lead will be increasingly challenged as states publicly that they do not track with generic medicine manufacturers, other new entrants compete for market this expenditure per product.26 High detailing the geographic scope of future share. This effect is already being seen as prices may be deterring bilateral, in- licences.

802 Bull World Health Organ 2015;93:799–805| doi: http://dx.doi.org/10.2471/BLT.15.157784 Policy & practice Danny J Edwards et al. Hepatitis C medicines

Regarding licensing, it is important turers early extends the time available the Eastern Mediterranean region and that pharmaceutical companies agree for technology transfer, thereby enabling India, including awareness-raising ac- to the most flexible terms possible, licencees to start production as soon tivities. Bristol-Myers Squibb is engaged for example, minimizing royalties, after product registration as possible. in a project aimed at raising awareness not placing restrictions on supply of Gilead has licensed medicines before in China, India and Japan. active pharmaceutical ingredients and product registration.33 To our knowl- allowing supply to as broad a range edge, no other pharmaceutical company Conclusion of countries as possible. This provides has engaged in pre-registration licensing generic medicine manufacturers with for HCV products. It is clear that treatment of hepatitis C the greatest potential to compete and Supporting awareness and is undergoing a revolution. It is not keep prices low. diagnosis enough however, to develop effective Market segmentation can broaden treatment. All actors in the global health the geographic scope of licences. Where Since most HCV are initially community need to ensure that these patent-holders may wish to retain mo- asymptomatic, it is also important to new products are available, accessible nopoly over higher income segments, raise sufficient awareness, reduce stigma, and affordable for all in need. This goal licences can limit markets generic man- and build screening and diagnostic ca- ultimately requires a multi-actor, multi- ufacturers can sell to. GlaxoSmithKline pacity to curb the epidemic. In addition pronged approach. and Pfizer, via their joint-venture ViiV to pricing and licensing, some compa- The lack of access strategies dis- Healthcare, have tested this approach nies disclosed details of programmes for closed for products under development in the context of HIV medicines with supporting local screening and diagnos- is concerning, especially those in phase the Medicines Patent Pool, segmenting tic capacity. It should be noted that such III clinical trials, which bear the greatest public and private markets for dolute- activities bring with them a significant chance of market entry. It is also con- gravir and introducing a tiered royalty risk of conflict of interest associated with cerning that some companies disclosed structure that enabled the inclusion of direct contact with patient organizations no access strategies for either currently more middle-income countries.32 or health-care professionals. Companies marketed products or products in the Plan access strategies early may seek to manage the risk of conflict pipeline. through the involvement of established As described, pharmaceutical Research-based companies should con- NGOs and/or WHO, aligning with the companies have central roles to play, sider developing access strategies such needs of ministries of health and inte- particularly with regard to ensuring as equitable pricing or voluntary licens- grating with existing programmes. affordability and voluntary licensing. ing earlier in a product’s lifecycle (for Merck & Co. is building screening The available evidence provided by example, in the later stages of research capacity in Latin America, aimed at companies so far suggests a need for and development). This could reduce the reducing the time taken for results to be more concerted, broader engagement time taken for products to reach those in received. Likewise, Roche, with strength in access strategies. ■ need. In the case of voluntary licensing, in diagnostics, is engaged in building agreeing terms with generic manufac- screening capacity in central Europe, Competing interests: None declared.

ملخص سبل احلصول عىل أدوية التهاب الكبد الفريويس “يس” إن التهاب الكبد الفريويس “يس” وباء منترش عىل مستوى العامل. “يس”، وهي AbbVie، وBristol-Myers Squibb، و وتشري تقديرات عدد املصابني هبذا املرض يف أنحاء العامل إىل ما Gilead، وJohnson & Johnson، وMerck & Co.، و يقارب 185 مليون شخص، يقيم معظمهم بالدول منخفضة Roche. وتتبنى هذه الرشكات جمموعة من املناهج لدعم عالج ” “ ومتوسطة الدخل. وقد أثمر التقدم الذي تم إحرازه ًمؤخرا يف التهاب الكبد الفريويس يس ، بام يشمل اسرتاتيجيات التسعري، تطوير العقاقري املضادة للفريوسات عن عالجات أكثر فاعلية ومنح الرتاخيص االختيارية، وبناء القدرات، والتربع بالعقاقري. ًا وأمانمع قابلية أعىل لتحملها من جانب املريض ً مقارنةبالعالجات كام ُجري مراجعةن ملدى مشاركة تلك الرشكات يف توفري سبل احلالية هلذا املرض. وتتيح هذه العالجات فرصة احلد من ذلك احلصول عىل املنتجات املتعلقة بالتهاب الكبد الفريويس “يس”. الوباء، رشيطة أن تتوفر بأسعار معقولة، وأن يزداد معدل إنتاج هذا ويف هذا الصدد، فإننا نقرتح بعض اإلجــراءات التي يمكن أن النوع من األدوية، باإلضافة إىل تعزيز برامج التوعية والفحص. تتخذها الرشكات كي تلعب ًا دورأكثر أمهية يف احلد من هذا الوباء: وتلعب رشكات املستحرضات الطبية ًا دور ًا حموري يف ذلك. )1( إعطاء األولوية للتقييامت املتعلقة بمعقولية األسعار؛ و)2( وقد بحثنا يف املنتجات التي تم تسويقها وقنوات توفري األدوية، وضع اسرتاتيجيات لتيسري احلصول عىل األدوية يف مرحلة مبكرة واسرتاتيجيات تيسري احلصول عليها لدى 20 رشكة من ضمن من دورة حياة املنتج؛ و) ( 3منح الرتاخيص للجهات ِّاملصنعة هلذه أكرب رشكات املستحرضات الطبية يف العامل، فوجدنا ست رشكات األنواع من األدوية. منها تعمل ًا حاليعىل تطوير أدوية عالج التهاب الكبد الفريويس

Bull World Health Organ 2015;93:799–805| doi: http://dx.doi.org/10.2471/BLT.15.157784 803 Policy & practice Hepatitis C medicines Danny J Edwards et al.

摘要 丙型肝炎药物的可及性 丙型肝炎是一种全球性流行病。据估计，全世界约 宝 (Bristol-Myers Squibb)、吉利德 (Gilead)、美国强 有 1.85 亿人受到感染，其中大多数人居住在中低收入 生 (Johnson & Johnson)、默克集团 (Merck & Co) 和罗 国家。目前，抗病毒药物研制取得了新进展，推出了 氏 (Roche)。这些公司采用一系列的方法支持丙型肝炎 新疗法，该疗法比现有的疾病疗法更加有效、安全且 治疗，包括定价策略、自愿授权、能力建设和药物捐赠。 耐受性更高。如果这些疗法价格实惠、这些药物的仿 我们概述了这些公司在解决丙型肝炎产品可及性方面 制药生产规模扩大并且公众意识和筛查项目增强，此 的承诺。我们为这些公司推荐了以下可行措施，它们 类疗法就为抑制该流行病提供了一种可能。 可采取这些措施在抑制该流行病中发挥更大的作用 ： 制药公司在其中发挥着核心作用。 一、将负担能力评估放在首位 ；二、在产品生命周期 我们调查了世界上最大的 20 家制药公司销售的 中及早制定药物可及性策略 ；三、向仿制药制造商提 产品、渠道和药物可及性策略。其中六家公司正在 供授权。 研制丙型肝炎药物 ：艾伯维 (AbbVie)、百时美施贵

Résumé Accès aux médicaments permettant de soigner l’hépatite C L’hépatite C est une épidémie mondiale. On estime à 185 millions le des médicaments pour soigner l’hépatite C: AbbVie, Bristol-Myers nombre d’individus infectés par ce virus dans le monde, la plupart vivant Squibb, Gilead, Johnson & Johnson, Merck & Co. et Roche. Ces sociétés dans des pays à revenu faible ou intermédiaire. Les récents progrès adoptent diverses approches pour faciliter le traitement de l’hépatite C, dans la mise au point de médicaments antiviraux ont conduit à des qui reposent notamment sur des stratégies de fixation des prix, l’octroi traitements plus efficaces, plus surs et mieux tolérés que les traitements volontaire de licences, un renforcement des capacités et des dons de existants pour soigner cette maladie. Ces traitements permettraient médicaments. Nous donnons un aperçu des efforts déployés par ces de freiner l’épidémie, à condition que leur coût soit abordable, que sociétés pour faciliter l’accès aux médicaments permettant de soigner la production de médicaments génériques soit intensifiée et que les l’hépatite C, et proposons des actions que peuvent mener ces sociétés programmes de sensibilisation et de dépistage soient renforcés. Les afin de jouer un plus grand rôle dans l’enraiement de cette épidémie: sociétés pharmaceutiques ont, à cet égard, un rôle central à jouer. (i) donner un degré de priorité élevé aux évaluations de l’accessibilité Nous avons examiné les produits commercialisés, les produits à l’étude économique; (ii) développer des stratégies d’accès au début du et les stratégies d’accès aux médicaments de 20 des plus importantes cycle de vie du produit; et (iii) octroyer des licences aux fabricants de sociétés pharmaceutiques mondiales. Six de ces sociétés développent médicaments génériques.

Резюме Доступ к лекарствам от гепатита С Гепатит С — заболевание уровня мировой эпидемии. По 20 крупнейшими фармацевтическими компаниями мира. Шесть оценкам специалистов, в мире гепатитом C заражены из них разрабатывают лекарства от гепатита С: AbbVie, Bristol- 185 миллионов человек. Большей частью они проживают в Myers Squibb, Gilead, Johnson & Johnson, Merck & Co. и Roche. странах с низким и средним уровнем дохода. Недавний прогресс Эти компании используют разнообразные подходы в вопросах в деле разработки антивирусных препаратов позволил создать терапии гепатита С, включая ценовые стратегии, добровольное новые методы лечения, которые эффективнее, безопаснее лицензирование, наращивание мощностей и предоставление и переносятся лучше, чем традиционные способы лечения лекарств на благотворительной основе. Мы предоставляем данного заболевания. Эти новые методы дают возможность обзор того, каким образом эти компании вовлечены в решение ограничить распространение эпидемии, однако они должны вопроса о доступности препаратов, предназначенных для быть доступны, а масштаб производства дженериков должен лечения гепатита С. Мы предлагаем компаниям, которые могут быть расширен. Кроме того, нам требуется укрепить программы играть более значимую роль в ограничении распространения по скрининговому обследованию и осведомленности о болезни. этой эпидемии, принять следующие меры: (i) поставить на Центральная роль в этом процессе отводится фармацевтическим первое место оценку доступности препаратов, (ii) разработать компаниям. Нами было проведено изучение имеющихся на стратегии по обеспечению доступности препарата на ранних рынке препаратов, ассортимента продукции и стратегий по этапах жизненного цикла товара и (iii) предоставить лицензии обеспечению доступности лекарственных средств, выпускаемых производителям дженериков.

Resumen Acceso a los medicamentos para tratar la hepatitis C La hepatitis C es una epidemia global. Se estima que, en todo el mundo, Estas terapias presentan una oportunidad para poner freno a la epidemia, hay 185 millones de personas infectadas, la mayoría de las cuales viven siempre y cuando sean asequibles, aumentar la producción genérica en países de ingresos bajos y medios. Los recientes avances en el de dichos medicamentos y reforzar los programas de sensibilización desarrollo de antivirales han producido terapias más efectivas, seguras y y detección. Las empresas farmacéuticas juegan un papel central. de mejor tolerancia que los tratamientos para la enfermedad existentes. Se examinaron los productos comercializados, tuberías y estrategias

804 Bull World Health Organ 2015;93:799–805| doi: http://dx.doi.org/10.2471/BLT.15.157784 Policy & practice Danny J Edwards et al. Hepatitis C medicines de acceso a los medicamentos de veinte de las mayores empresas medicamentos. Ofrecemos una visión general del compromiso de farmacéuticas del mundo. Seis de estas empresas están desarrollando estas empresas a la hora de ofrecer acceso a los productos para tratar la medicamentos para tratar la hepatitis C: AbbVie, Bristol-Myers Squibb, hepatitis C. Sugerimos acciones que las empresas pueden llevar a cabo Gilead, Johnson & Johnson, Merck & Co. y Roche. Estas empresas para tener un papel más importante a la hora de frenar esta epidemia: (i) emplean una gama de enfoques para apoyar el tratamiento para la dar prioridad a los criterios de asequibilidad; (ii) desarrollar estrategias de hepatitis C, incluyendo las estrategias de fijación de precios, la concesión acceso al principio del ciclo de vida del producto; y (iii) ofrecer licencias voluntaria de licencias, la creación de capacidad y las donaciones de a los fabricantes de medicamentos genéricos.

References 1. Guidelines for the screening, care and treatment of persons with Hepatitis 19. HCV developing world strategy [Internet]. New York: Bristol-Myers Squibb; C infection [Internet]. Geneva: World Health Organization; 2014. Available 2015. Available from: http://www.bms.com/responsibility/access to from: http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_ medicines/Pages/HCV-developing-world-strategy.aspx [cited 2015 Mar 13]. eng.pdf?ua=1andua=1 [cited 2015 Mar 13]. 20. Reeves A. Gilead, AbbVie Hep C price cuts seen hitting sales. Investor’s 2. Hepatitis C fact sheet No 164 [Internet]. Geneva: World Health Organization; Business Daily. 2015 Jan 21. Available from: http://news.investors.com/ 2015. Available from: http://www.who.int/mediacentre/factsheets/fs164/ technology/012115-735507-hepatitis-c-drugs-gilead-abbvie-may-miss- en/ [cited 2015 Feb 27]. estimates.htm [cited 2015 Feb 27]. 3. Graham CS, Swan T. A path to eradication of hepatitis C in low- and middle- 21. Buente M, Danner S, Ehrhardt M, Fernandes F. Pharma emerging market income countries. Antiviral Res. 2015 Jul;119:89–96. doi: http://dx.doi. 2.0: how emerging markets are driving the transformation of the org/10.1016/j.antiviral.2015.01.004 PMID: 25615583 pharmaceutical industry. New York: Strategy&; 2013. 4. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology 22. Barriers to access and scale up of hepatitis C (HCV) treatment: Gilead’s and genotype distribution of the infection. J Hepatol. 2014 anti-diversion program. Geneva: Medécins Sans Frontières; 2015. Available Nov;61(1) Suppl:S45–57. doi: http://dx.doi.org/10.1016/j.jhep.2014.07.027 from: http://www.msfaccess.org/sites/default/files/HepC_Gilead_anti- PMID: 25086286 diversion_FINAL.pdf [cited 2015 Mar 19]. 5. Sadler MD, Lee SS. Revolution in hepatitis C antiviral therapy. Br Med Bull. 23. Gilead Sciences, Inc. earnings: we’ll make up for it in volume [Internet]. 2015 Mar;113(1):31–44. doi: http://dx.doi.org/10.1093/bmb/ldv004 PMID: Alexandria: The Motley Fool; 2015. Available from: http://www.fool.com/ 25680808 investing/general/2015/02/03/gilead-sciences-inc-earnings-well-make-up- 6. 1998: Big pharma versus Nelson Mandela [Internet]. Geneva: Medécins Sans for-it-i.aspx [cited 2015 Mar 13]. Frontières Access Campaign; 2009. Available from: http://www.msfaccess. 24. Londeix P. New treatments for hepatitis C virus, strategies for achieving org/content/1998-big-pharma-versus-nelson-mandela [cited 2015 Feb 27]. universal access. Brussels: Médecins du Monde; 2014. Available from: http:// 7. Global health observatory, HIV/AIDS [Internet]. Geneva: World Health hepcoalition.org/IMG/pdf/web_daas_strategies_for_achieving_universal_ Organization; 2015. Available from: http://www.who.int/gho/hiv/en/ [cited access_en.pdf [cited 2015 Feb 27]. 2015 Feb 27]. 25. Hill A, Khoo S, Fortunak J, Simmons B, Ford N. Minimum costs for producing 8. Sumner A. Global poverty, aid, and middle-income countries: are the hepatitis C direct-acting antivirals for use in large-scale treatment access country classifications moribund or is global poverty in the process of programs in developing countries. Clin Infect Dis. 2014 Apr;58(7):928–36. “nationalizing”? Helsinki: UNU-WIDER; 2013. p. 37. doi: http://dx.doi.org/10.1093/cid/ciu012 PMID: 24399087 9. Pezzini M. An emerging middle class [Internet]. Paris: OECD Observer; 2012. 26. Gilead Sciences Q1’15 form 10-Q [Internet]. Available from: http://investors. Available from: http://www.oecdobserver.org/news/fullstory.php/aid/3681/ gilead.com/phoenix.zhtml?c=69964&p=irol-earnings [cited 2015 Jul 7]. An_emerging_middle_class.html [cited 2015 Feb 27]. 27. Waning B, Diedrichsen E, Moon S. A lifeline to treatment: the role of Indian 10. Hepatitis C medicines: technology and market landscape. Geneva: World generic manufacturers in supplying antiretroviral medicines to developing Health Organization; 2015. Available from: http://unitaid.org/images/ countries. J Int AIDS Soc. 2010;13(1):35. doi: http://dx.doi.org/10.1186/1758- marketdynamics/publications/HCV_Meds_Landscape_Feb2015.pdf [cited 2652-13-35 PMID: 20840741 2015 Aug 18]. 28. License agreement, Gilead Sciences Limited: sofosbuvir and ledipasvir 11. Access to Medicine Index. Haarlem, Netherlands: Access to Medicine [Internet]. Foster City: Gilead; 2014. Available from: http://www.gilead. Foundation; 2014. Available from: http://www.accesstomedicineindex.org/ com/~/media/files/pdfs/other/2014_original_hcv_licensing_agreement. sites/2015.atmindex.org/files/2014_accesstomedicineindex_fullreport_ pdf?la=en [cited 2015 Jul 8]. clickablepdf.pdf [cited 2015 Oct 5]. 29. KEI welcomes the Gilead HCV licenses, as a step to expand access to 12. Methodology report 2013 for the 2014 Access to Medicine Index. Haarlem: treatment. Notes challenges that remain [Internet]. Washington: Knowledge The Access to Medicine Foundation; 2013. Available from: http://www. Ecology International; 2014. Available from: http://www.keionline.org/ accesstomedicineindex.org/sites/2015.atmindex.org/files/general/ node/2082 [cited 2015 Feb 27]. methodology_report_2013_for_the_2014_access_to_medicine_index.pdf 30. Gilead’s license on hepatitis C drugs, Sofosbuvir and Ledipasvir: a Fool’s [cited 2015 Jul 6]. Bargain – Myths and facts [Internet]. hepCoalition; 2014. Available from: 13. Nguyen DL, Hu K-Q. Clinical monitoring of chronic hepatitis C based on its http://www.hepcoalition.org/news/article/gilead-s-license-on-hepatitis-c natural history and therapy. N Am J Med Sci (Boston). 2014;7(1):21–7. PMID: [cited 2015 Sep 23]. 25580186 31. Rajagopal D. Natco Pharma launches hepatitis C drug in Nepal [Internet]. 14. Kim Y, Ahn SH, Han K-H. Emerging therapies for hepatitis C. Gut Liver. 2014 India: The Economic Times; 2015. Available from: http://articles. Sep;8(5):471–9. doi: http://dx.doi.org/10.5009/gnl14083 PMID: 25228970 economictimes.indiatimes.com/2015-03-10/news/59969949_1_us-based- 15. WHO moves to improve access to lifesaving medicines for hepatitis gilead-sciences-natco-pharma-sofosbuvir [cited 2015 Mar 30]. C, drug-resistant TB and cancers [Internet]. Geneva: World Health 32. Medicines patent pool, ViiV Healthcare sign licence for the most Organization; 2015. Available from: http://www.who.int/mediacentre/ recent HIV medicine to have received regulatory approval [Internet]. news/releases/2015/new-essential-medicines-list/en/ [cited 2015 Jul 7]. Geneva: Medicines Patent Pool; 2014. Available from: http://www. 16. Staton T. Another one bites the dust: Merck cans hep C fighter Victrelis as new medicinespatentpool.org/medicines-patent-pool-viiv-healthcare-sign- meds take flight [Internet]. Washington: FiercePharma; 2015. Available from: licence-for-the-most-recent-hiv-medicine-to-have-received-regulatory- http://www.fiercepharma.com/story/another-one-bites-dust-merck-cans- approval/ [cited 2015 Mar 13]. hep-c-fighter-victrelis-new-meds-take-fli/2015-01-21 [cited 2015 Mar 3]. 33. Gilead expands hepatitis C generic licensing agreements to include 17. Boehringer Ingelheim statement on hepatitis C drug development investigational pan-genotypic agent [Internet]. Foster City: Gilead; 2015. [Internet]. Ingelheim am Rhein: Boehringer Ingelheim; 2014. Available Available from: http://www.gilead.com/news/press-releases/2015/1/ from: http://www.boehringer-ingelheim.com/news/news_releases/ gilead-expands-hepatitis-c-generic-licensing-agreements-to-include- press_releases/2014/20_june_2014_hepatitis.html [cited 2015 Feb 27]. investigational-pangenotypic-agent [cited 2015 Feb 27]. 18. Hepatitis C treatment [Internet]. New York: Hep Magazine; 2015. Available from: http://www.hepmag.com/articles/2512_13704.shtml [cited 2015 Sep 23].

Bull World Health Organ 2015;93:799–805| doi: http://dx.doi.org/10.2471/BLT.15.157784 805