Ellen 't Hoen

Driving a decade of change: HIV/AIDS, patents and access to medicines for all

Since 2000, access to antiretroviral drugs to treat HIV infection has dramatically increased to reach more than five million people in developing countries. Essential to this achievement was the dramatic reduction in antiretroviral prices, a result of global political mobilization that cleared the way for competitive production of generic versions of widely patented medicines.Global trade rules agreed upon in 1994 required many developing countries to begin offering patents on medicines for the first time. Government and civil society reaction to expected increases in drug prices precipitated a series of events challenging these rules, culminating in the 2001 World Trade Organizations Doha Declaration on the Agreement on Trade-Related Aspects of Intellectual Property Rights and Public Health. The Declaration affirmed that patent rules should be interpreted and implemented to protect public health and to promote access to medicines for all. Since Doha, more than 60 low- and middle-income countries have procured generic versions of patented medicines on a large scale.Despite these changes, however, a treatment timebomb awaits. First, increasing numbers of people need access to newer antiretrovirals, but treatment costs are rising since new ARVs are likely to be more widely patented in developing countries. Second, policy space to produce or import generic versions of patented medicines is shrinking in some developing countries. Third, funding for medicines is falling far short of needs. Expanded use of the existing flexibilities in patent law and new models to address the second wave of the access to medicines crisis are required.One promising new mechanism is the UNITAID-supported Medicines Patent Pool, which seeks to facilitate access to patents to enable competitive generic medicines production and the development of improved products. Such innovative approaches are possible today due to the previous decade of AIDS activism. However, the Pool is just one of a broad set of policies needed to ensure access to medicines for all; other key measures include sufficient and reliable financing, research and development of new products targeted for use in resource-poor settings, and use of patent law flexibilities. Governments must live up to their obligations to protect access to medicines as a fundamental component of the human right to health.

Essential medicines for universal health coverage.

Author(s): Wirtz, Veronika J; Hogerzeil, Hans V; Gray, Andrew L; Bigdeli, Maryam; de Joncheere, Cornelis P; Ewen, Margaret A; Gyansa-Lutterodt, Martha; Jing, Sun; Luiza, Vera L; Mbindyo, Regina M; Moller, Helene; Moucheraud, Corrina; Pecoul, Bernard; Rago, Lembit; Rashidian, Arash; Ross-Degnan, Dennis; Stephens, Peter N; Teerawattananon, Yot; t Hoen, Ellen FM; Wagner, Anita K; Yadav, Prashant; Reich, Michael R

Innovation and Access to Medicines for Neglected Populations: Could a Treaty Address a Broken Pharmaceutical R&D System?

As part of a cluster of articles leading up to the 2012 World Health Report and critically reflecting on the theme of “no health without research,” Suerie Moon and colleagues argue for a global health R&D treaty to improve innovation in new medicines and strengthening affordability, sustainable financing, efficiency in innovation, and equitable health-centered governance.

Burden of HIV-Related Cytomegalovirus Retinitis in Resource-Limited Settings: A Systematic Review

BACKGROUNDnCytomegalovirus (CMV) is a late-stage opportunistic infection in people living with human immunodeficiency virus (HIV)/AIDS. Lack of ophthalmological diagnostic skills, lack of convenient CMV treatment, and increasing access to antiretroviral therapy have all contributed to an assumption that CMV retinitis is no longer a concern in low- and middle-income settings.nnnMETHODSnWe conducted a systematic review and meta-analysis of published and unpublished studies reporting prevalence of CMV retinitis in low- and middle-income countries. Eligible studies assessed the occurrence of CMV retinitis by funduscopic examination within a cohort of at least 10 HIV-positive adult patients.nnnRESULTSnWe identified 65 studies from 24 countries, mainly in Asia (39 studies, 12 931 patients) and Africa (18 studies, 4325 patients). By region, the highest prevalence was observed in Asia with a pooled prevalence of 14.0% (11.8%-16.2%). Almost a third (31.6%, 95% confidence interval [CI], 27.6%-35.8%) had vision loss in 1 or both eyes. Few studies reported immune status, but where reported CD4 count at diagnosis of CMV retinitis was <50 cells/µL in 73.4% of cases. There was no clear pattern of prevalence over time, which was similar for the period 1993-2002 (11.8%; 95% CI, 8%-15.7%) and 2009-2013 (17.6%; 95% CI, 12.6%-22.7%).nnnCONCLUSIONSnPrevalence of CMV retinitis in resource low- and middle-income countries, notably Asian countries, remains high, and routine retinal screening of late presenting HIV-positive patients should be considered. HIV programs must ensure capacity to manage the needs of patients who present late for care.

A quiet revolution in global public health: The World Health Organization’s Prequalification of Medicines Programme

Problems with the quality of medicines abound in countries where regulatory and legal oversight are weak, where medicines are unaffordable to most, and where the official supply often fails to reach patients. Quality is important to ensure effective treatment, to maintain patient and health-care worker confidence in treatment, and to prevent the development of resistance. In 2001, the WHO established the Prequalification of Medicines Programme in response to the need to select good-quality medicines for UN procurement. Member States of the WHO had requested its assistance in assessing the quality of low-cost generic medicines that were becoming increasingly available especially in treatments for HIV/AIDS. From a public health perspective, WHO PQP’s greatest achievement is improved quality of life-saving medicines used today by millions of people in developing countries. Prequalification has made it possible to believe that everyone in the world will have access to safe, effective, and affordable medicines. Yet despite its track record and recognized importance to health, funding for the programme remains uncertain.

The UNITAID Patent Pool Initiative: Bringing Patents Together for the Common Good

Developing and delivering appropriate, affordable, well-adapted medicines for HIV/AIDS remains an urgent challenge: as first-line therapies fail, increasing numbers of people require costly second-line therapy; one-third of ARVs are not available in pediatric formulations; and certain key first- and second-line triple fixed-dose combinations do not exist or sufficient suppliers are lacking. UNITAID aims to help solve these problems through an innovative initiative for the collective management of intellectual property (IP) rights – a patent pool for HIV medicines. The idea behind a patent pool is that patent holders - companies, governments, researchers or universities - voluntarily offer, under certain conditions, the IP related to their inventions to the patent pool. Any company that wants to use the IP to produce or develop medicines can seek a license from the pool against the payment of royalties, and may then produce the medicines for use in developing countries (conditional upon meeting agreed quality standards). The patent pool will be a voluntary mechanism, meaning its success will largely depend on the willingness of pharmaceutical companies to participate and commit their IP to the pool. Generic producers must also be willing to cooperate. The pool has the potential to provide benefits to all.

Essential medicines are still essential

On Oct 21, WHO published the full report of the 20th Expert Committee on the Selection and Use of Essential Medicines, with its new WHO Model List of Essential Medicines (EML). The new list includes recently developed medicines for drug-resistant tuberculosis (bedaquiline and delamanid), a number of new cancer treatments (such as imatinib, rituximab, and trastuzumab), and, perhaps most controversially, new direct-acting antiviral drugs (DAA) for the treatment of hepatitis C (sofosbuvir, simeprevir, daclatasvir, ledipasvir, and ombitasvir). Several of these medicines are very expensive. For example, the new medicines to treat hepatitis C are priced up to US

A victory for global public health in the Indian Supreme Court

95 000 per 12-week course of treatment, and their primary patents will only expire in 2024–30. Despite the ability of some payers and intermediaries to negotiate large discounts, even high-income countries are struggling to pay for broad access to these treatments. It is not the fi rst time that WHO has added expensive medicines to the Model List. In 2002, the agency included 12 antiretroviral medicines for HIV/AIDS that were patented in many countries, to focus global attention on a major global public health need and to stimulate interventions to expand access to these lifesaving medicines. These products were unaff ordable for almost all countries at that time. The new Model List now expands further into other therapeutic areas. The recent inclusion of new expensive medicines has raised many questions. Has the original concept of essential medicines lost its original relevance as a list of basic medicines for resource-constrained settings? Should the list include medicines not yet authorised by stringent regulatory authorities or not easily available? Should the list include medicines for off -label indications? Should the list automatically include any medicine mentioned in a WHO treatment guideline? Previous expert committees’ reports have provided some answers to these questions. For instance, in 2013 bevacizumab was included for the treatment of macular degeneration, on the basis of available evidence but in the absence of regulatory approval for that specifi c indication. In 2005, child-friendly formulations of zinc sulfate tablets were added, even though such dispersible dosage forms were not widely available at the time. For many years, the WHO Model List has been viewed by some as applicable only to resource-constrained settings, and was assumed to include only the most basic medicines. This is a profound misunderstanding. The same principle of a limited list of cost-eff ective services underpins the logic of managed care institutions, hospital formularies, and reimbursement lists. The idea of selecting a limited list of essential medicines applies in all countries and in a variety of settings. We therefore believe that the inclusion of the newly listed cancer treatments, as well as the much-needed options for drug-resistant tuberculosis, is consistent with the defi nition of essential medicines. In 2002, WHO decided that cost alone would not prevent a medicine from being listed, if other criteria of safety, effi cacy, and comparative cost-eff ectiveness were fulfi lled. Yet the 2015 decision to include a range of DAAs for hepatitis C introduces a new approach of listing several very eff ective medicines, rather than selecting a single regimen. According to the Expert Committee, “Inclusion on the EML of all DAAs proposed in the applications aims at promoting competition among available alternatives and allowing for the selection of optimal combination treatment regimens, which may or may not be existing fi xed-dose combinations”. The Committee also noted that WHO is working to promote the rapid

Indian hepatitis C drug patent decision shakes public health community

On 1 April of this year, the Indian Supreme Court upheld the decision of the Indian Patent Office to refuse the patent grant for Novartis imatinib mesylate (Gleevec). The patent application failed to meet the requirements for patentability under Indian law. The global public health community followed the case closely. Its outcome could affect the Indian generics industry - an important supplier of low cost medicines to the developing world.On 1 April of this year, the Indian Supreme Court upheld the decision of the Indian Patent Office to refuse the patent grant for Novartis imatinib mesylate (Gleevec). The patent application failed to meet the requirements for patentability under Indian law. The global public health community followed the case closely. Its outcome could affect the Indian generics industry – an important supplier of low cost medicines to the developing world.

Regulatory framework for access to safe, effective quality medicines

On May 9, 2016, the Indian Patent Office granted the US pharmaceutical company Gilead a patent for sofosbuvir, a direct-acting antiviral for the treatment of hepatitis C virus (HCV). The decision to grant the patent reversed an earlier decision by the Indian Patent Office to reject the application after civil society organisations and generic manufacturers had filed a formal opposition to the patent application. The new sofosbuvir patent decision is again raising concerns among public health advocates. HCV infection can lead to lethal liver disease if left untreated. WHO estimates that 130–150 million people worldwide have chronic HCV infection, although recent estimates suggest this figure could be lower, at around 80 million. WHO has laid out a global strategy for the treatment and elimination of HCV and has added sofosbuvir and other HCV medicines to the WHO Model List of Essential Medicines. The implementation of such an ambitious strategy will depend on the availability of affordable medicines. Affordability is central to the HCV issue. The price of a 12-week sofosbuvir treatment course of up to US