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A close-up of packets of pills. (Photo: PATH/Christopher Nelson) In November 2015, United Nations (UN) Secretary-General Ban Ki-moon convened a High-Level Panel on Access to Medicinesto discuss and develop solutions to promote innovation and access to essential medicines, vaccines, diagnostics, and other health technologies needed to ensure health and well-being around the world. This panel comes on the heels of the UN General Assembly formally adopting the Sustainable Development Goals (SDGs)—goal three of which is to “ensure healthy lives and promote well-being for all at all ages”—and is designed to consider ways in which intellectual property (IP) protections, trade rules, and international human rights law might affect global access to medicine and the ability of the international community to achieve SDG three by 2030. The panel also comes at a time when the United States and the international community are considering one of the most ambitious trade agendas in the last several years. The Trans-Pacific Partnership (TPP), the largest regional trade agreement in history, linking 11 Pacific-rim countries that make up 40 percent of the world’s economy, was finalized in October 2015 and is currently under review by the US Congress. The agreement has stronger IP protections for pharmaceutical products than those included in previous regional and bilateral trade agreements—including twelve years of data protection for new biologics and the ability to evergreen certain pharmaceutical patents—which may impact timely access to generic medicines in TPP countries. The US is also in the process of negotiating the Trans-Atlantic Trade and Investment Partnership (TTIP), which would reduce tariffs and codify trade-related standards between the United States and the European Union. Details of this agreement have not yet been made public. (To read more about the potential impact of TPP on access to medicine, visit GHTC’s blog .) Though minimum standards for patents and IP protections have been included in trade agreements since 1995, when the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) was approved by the World Trade Organization (WTO), certain actions have carved out exceptions to protect public health and support low- and middle-income countries. The Doha Declaration on TRIPS and Public Health formally clarified that TRIPS IP protections for pharmaceuticals should not prevent countries from protecting public health and promoting access to medicine. It also affirmed flexibilities for least developed countries (LDCs), as designated by the UN, to gradually enforce IP protections for pharmaceuticals, including provisions around compulsory licensing of generic medications, and established January 1, 2016, as the deadline for LDCs to implement enforcement of pharmaceutical patents. The US May 10th Agreement established congressional intent for TRIPS flexibilities, as expressed in the Doha Declaration, to be reflected in all US trade negotiations. With the on-ramp for LDCs to enforce pharmaceutical patents set to expire at the start of the new year, in November, the WTO committee on IP rights agreed to extend the provision allowing LDCs to avoid applying and enforcing IP rights on pharmaceutical products until 2033. In a June 2015 letter to the WTO, advocates argued that, “Many LDCs (at least 25 countries) have relied on the…pharmaceutical product [exemption] to declare patents unenforceable as well as to exempt pharmaceutical products from patent and test data obligations, thereby allowing them to import critical treatments such as medicines for their national HIV and AIDS treatment programs” at affordable prices. Because “the public health crisis in LDCs is a long-term challenge that will endure at least as long as these countries remain LDCs,” an extension of the on-ramp is critical to “provide suppliers, procurers and donors of affordable medicines in LDCs the clarity and certainty to confidently manufacture, export and import generic medicines.” Countries with strong pharmaceutical industries, like the United States, negotiated to make the extension time-bound to 2033 in lieu of the permanent extension sought by LDCs and their advocates. It is with this backdrop that the UN High-Level Panel on Access to Medicines begins its work. The UN Secretary-General has appointed members of the panel—with representatives from both developed and low- and middle-income countries. Further, a group of expert advisors—from civil society, the private sector, and academia—has been established to help guide the Panel’s work. Several documents including a Report on HIV and the Law are cited as background for the Panel’s work. After the first in-person meeting of the panel in December, the group opened a call for contributions by interested stakeholders “that address the misalignment between the rights of inventors, international human rights law, trade rules and public health where it impedes the innovation of and access to health technologies.” The panel will discuss these contributions at two public hearings in March, which will help to guide the development of their formal report to the Secretary-General, expected to be finalized in early June. To ensure that essential global health technologies get into the hands of populations in need, promoting access to medicines and global health tools is just as critical as supporting the research and development that drives these new innovations. GHTC will be closely monitoring the work of the High-Level Panel and looks forward to contributing to the public hearings in March.

Last monPhoto: PATH/Mike Wangth, the World Health Organization (WHO) convened experts to determine which emerging diseases could become “the next Ebola”—those pathogens most likely to cause the next major epidemic. The panel focused on diseases for which there are limited medical countermeasures, with the goal of galvanizing research and development (R&D) for the tools needed to prevent and control future outbreaks. Many have lauded the acceleration of Ebola R&D since the onset of the West Africa outbreak, with experimental treatments made available through emergency use authorizations, and stages of vaccine development and manufacturing progressing in months, rather than years. However, these last minute investments are costly and will not always be successful—underscoring the importance of having tools to prevent, detect, and treat these emerging pathogens before we need them.The list of emerging diseases identified by the WHO includes Crimean Congo hemorrhagic fever (CCHF), Ebola and Marburg, Lassa fever, Rift Valley fever (RVF), Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), and Nipah virus. There are some striking similarities between these eight pathogens: all eight are viral, zoonotic, and there are no approved vaccines, point-of-care diagnostics, or treatments for any of the eight diseases.Below, GHTC provides an overview of the eight diseases and the state of R&D for diagnostics, drugs, vaccines and other technologies against them.Crimean-Congo hemorrhagic fever Why should we be concerned? CCHF is tick-borne virus that is fatal in up to 40 percent of cases. First reported in Tajikistan in the 12th century, CCHF is now endemic in the Balkans, the Middle East, central and south Asia, and Africa. A hemorrhagic fever, CCHF affects many parts of the body and can weaken blood vessels. Initial symptoms are often nonspecific—fever, headache, muscle and back pain, vomiting, diarrhea—but as the disease progresses, patients may experience light sensitivity, redness of the face and throat, jaundice, depression, exhaustion, and mood swings.CCHF can be found in a myriad of both wild and domestic animals, including cattle, sheep, goats, horses, hedgehogs, and even ostriches. While most human cases are attributable to either tick bites or interactions with livestock, it can be transmitted between humans through contact with body fluids.Where does R&D stand? There are several laboratory tests to diagnose CCHF, however, diagnosing the disease in low-resource settings presents challenges. Blood and tissue samples are contagious and should not be handled outside of “maximum biological containment conditions,” according to the WHO.There are currently no vaccines or drugs approved to treat CCHF. Current treatment involves managing the symptoms, including the provision of fluids and electrolytes. Ribavirin, an antiviral hepatitis C medicine, is often used to treat CCHF, although clinical trials to demonstrate its efficacy have been inconclusive. There is a vaccine candidate in early-stage development which has proved effective in mice.Ebola and Marburg virus disease Why should we be concerned? It is possible that Ebola could literally be the “next Ebola” outbreak. Marburg virus, a close relative of Ebola, is another leading contender. Both Ebola and Marburg viruses reside in monkeys and bats and can jump from animals to humans, however, most cases result from human-to-human transmission, through exposure to bodily fluids.Ebola and Marburg are also hemorrhagic fevers, and the symptoms—fever, headache, malaise, diarrhea, abdominal pain, nausea, vomiting—are easily confused with malaria, typhoid fever, or meningitis, depending on the local disease burden. Cases of Marburg and Ebola can only be confirmed in laboratory settings, and similar to CCHF, patient samples are a major biosafety risk if handled inappropriately. In late 2014, the WHO Prequalification Program instated an emergency mechanism to allow for rapid review of Ebola diagnostics, resulting in the approval of six diagnostics for emergency use. The WHO, in partnership with Médecins Sans Frontières and FIND, also convened diagnostic companies to plan for the accelerated development of rapid, point-of-care diagnostics.Where does R&D stand? The recent West African outbreak galvanized US$165 million for Ebola R&D, and several Ebola vaccine and drug candidates in development are also intended to prevent and treat Marburg. However, to stymie the next outbreak, sustained investment in Ebola and Marburg R&D is needed for the advanced development, regulatory review, introduction, and roll-out of promising vaccines, drugs, and diagnostics.Lassa fever Why should we be concerned? Lassa fever is primarily transmitted to humans through the bodily fluids of either rats or other humans. While 80 percent of those infected are asymptomatic, 20 percent experience the standard set of symptoms associated with hemorrhagic fevers, and in severe cases, swelling of the face and brain, shock and seizures, and deafness.Where does R&D stand? Cases can only be confirmed in the lab, and there are no vaccines or drugs approved to specifically treat or prevent Lassa. The aforementioned hepatitis C drug—ribavirin—is also used to treat Lassa fever, with again only limited data available on its efficacy. The primary method of Lassa prevention and control involves promoting hygiene and protecting homes and food from rodents.Rift Valley Fever Why should we be concerned? RVF is found in sub-Saharan Africa and the Arabian Peninsula. Most cases are either asymptomatic or mild with nonspecific symptoms, including fever, muscle and joint pain, and headache. Eight percent of patients experience more severe symptoms which can include lesions in the eye and loss of vision; swelling of the brain (encephalitis); or a hemorrhagic fever.Sheep, cattle, camels, and goats can all become infected with RVF and most human cases are attributable to contact with infected animal tissue, through slaughter, disposal, or veterinary care. It is believed that humans can also become infected through consumption of unpasteurized dairy products or mosquito bites. No cases of human-to-human transmission have been reported.Where does R&D stand? RVF can only be diagnosed in the lab, and the range of symptoms makes it difficult to detect. Treatment is supportive, and is tailored to the patients’ symptoms. The US Centers for Disease Control and Prevention have developed an experimental vaccine against RVF for use in animals. Initial studies have been encouraging, suggesting that the vaccine is safe, effective, and inexpensive.Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome coronaviruses Why should we be concerned? MERS and SARS affect the upper respiratory and gastrointestinal systems, and the two coronaviruses have similar symptoms, including fever, cough, and shortness of breath. While MERS is less contagious than SARS, it is four times more deadly, killing up to 40 percent of those infected."Camels in the kingdom [of Saudi Arabia] are like dairy cows, beef cows, racehorses, pulling horses, beloved Labradors, and living daily reminders of holy scripture, all in one." Cynthia Gorney, National Geographic (Photo: PATH/Teresa Guillien)SARS was first identified in 2002, infecting 8,000 people, primarily in China, Hong Kong, and Taiwan. However, the outbreak lasted less than a year, and there have been no new cases since 2004. Since the 2012 emergence of MERS, more than 1,600 cases have been reported in 26 countries. Most cases, however, are found in the Arabian Peninsula, and all other cases are attributed to Middle East travel.While both viruses are found in bats, most cases of these airborne diseases come from human-to-human transmission. MERS is also found in camels and camel-to-human transmission is believed to be a significant source of new cases. In the Arabian Peninsula, 12 percent of camels are infected with MERS at any given time, however, the virus merely causes an innocuous cold in camels.Where does R&D stand? There are no approved vaccines or drugs for either SARS or MERS, and both must be confirmed in the lab. Without effective antivirals against the coronaviruses, treatment involves addressing the symptoms. Convalescent blood plasma therapy—in which the blood plasma of survivors, containing antibodies against the virus, is provided to patients—has been used experimentally for both diseases, and decreased the SARS fatality rate by 23 percent. A number of treatments for MERS are in development, however, none have progressed to human trials. There are several MERS vaccine candidates, and human trials are planned for at least one. Additionally, a MERS vaccine for camels has undergone an initial, promising round of testing. GHTC member Sabin Vaccine Institute is also working on a vaccine for SARS.Nipah Why should we be concerned? Nipah virus was first identified in 1999, during an outbreak of the illness in Malaysia and Singapore, in which nearly 300 cases and 100 deaths were recorded, primarily among pig farmers. To stop the spread of Nipah, more than 1 million pigs were slaughtered. Since then, regular outbreaks have occurred in Bangladesh and India.Nipah impacts the nervous and respiratory systems, causing inflammation of the brain, sluggishness, disorientation, and encephalitis. Nipah kills 40 percent of those infected, and survivors often experience long-term effects, including convulsions and personality change.Where does R&D stand? Diagnosing Nipah virus requires multiple laboratory tests. As is the case with CCHF and Lassa fever, the drug ribavirin has been used to treat Nipah, however, its efficacy has not been confirmed. While there is no vaccine to prevent Nipah, human antibodies against it have been tested in ferrets, and results suggest that these antibodies could provide protection against the virus.

Photo: National Institute of Allergy and Infectious Diseases (NIAID) Gavi, the Vaccine Alliance, signed an advanced purchase commitment, pledging to spend US$5 million on an Ebola vaccine currently under development by pharmaceutical company Merck & Co. The vaccine candidate was tested on 4,000 people in Guinea last year, and the results were promising: despite all participants having close contact with at least one Ebola patient, none developed the disease more than ten days after vaccination (several days are required for a vaccine to confer protection). The vaccine candidate—VSV-EBOV—was developed and tested in partnership with the Canadian and US governments, however, without the urgency of an outbreak, public-sector support moving forward is limited. The agreement guarantees that there will be a market for the vaccine, assuring Merck & Co. that they can recover investments in advanced development and manufacturing. This move will also enable Gavi to establish a stockpile of the vaccine so that it can be rapidly deployed in future outbreaks. New research suggests that 2.6 million stillbirths occur each year, 420,000 of which are attributable to malaria or syphilis infections. These results underscore the need for testing and treatment of malaria and syphilis in pregnant women, particularly in endemic regions. Fortunately, there are low-cost interventions that could drastically reduce adverse pregnancy outcomes attributable to malaria and syphilis infections. The malaria parasite is able to reside in the placenta, even when undetectable in the mother’s blood, and thus, preventative treatment for malaria is critical. The antimalarial sulphadoxine-pyrimethamine, which costs a mere $0.20 per patient, is recommended for use in pregnant women in endemic areas. In east and southern Africa, an estimated 5 percent of pregnant women are infected with syphilis and in Tanzania, up to half of stillbirths are caused by syphilis. However, one dose of penicillin can cure both maternal and congenital syphilis and prevent stillbirth—at just $1.40 per person. While malaria- and syphilis-related stillbirths can be prevented with the scale-up of existing medicines, many more could be prevented with interventions that are not appropriate for low-resource settings, which is particularly concerning as 98 percent of stillbirths occur in low- and middle-income countries. Further, the cause of stillbirth is often unknown, according to the Global Alliance to Prevent Prematurity and Stillbirth, and additional research is needed to determine and address these causes. There is little incentive for pharmaceutical companies to invest in antimicrobial research and development (R&D): antibiotics are prescribed for short periods of time and competition among antibiotics keeps prices low. However, with the spread of drug resistance, the “[financial] value assigned to antibiotics and diagnostics often does not reflect the benefits they bring to society,” according to a declaration authored by 80 pharmaceutical and diagnostic companies and released at this year‘s World Economic Forum in Davos, Switzerland. The declaration calls on governments to work with the pharmaceutical industry to spur antimicrobial R&D, identifying innovative financing mechanisms, including prizes (a Market Entry Rewards initiative) and intellectual property–related incentives. In response, the companies pledge to invest in R&D for new antibiotics, as well as improved diagnostics to prevent the unnecessary use of antibiotics (i.e., for viral conditions).

With the New Year underway, GHTC is looking forward to a busy spring of multilateral organization meetings—with a number of them impacting global health research and development (R&D). First on the agenda is the World Health Organization (WHO) Executive Board (EB) meeting on January 25–30 in Geneva, where the EB will receive updates on a number of topics and make important decisions, particularly around how to proceed with the next steps of the Consultative Expert Working Group on Research and Development: Financing and Coordination (CEWG) process. The full provisional agenda is available here, but below, GHTC’s Matt Robinson highlights what you can expect on global health R&D related topics. WHO Executive Board (Photo: NCD Alliance) Agenda item #7 – Promoting health through the life course – Tuesday, January 26 7.1 – Monitoring of the achievement of the health-related Millennium Development Goals (MDGs) – Update to the Board The development of indicators to monitor progress toward the health-related MDGs has been a key priority for the WHO. This update to the Board outlines the current slate of health indicators, including indicator 8.E on affordable access to medicines. 7.2 – Health in the 2030 agenda for sustainable development – Update to the Board In this session the WHO Secretariat will present a report tracing the development of the Sustainable Development Goals (SDGs), outlining key differences from the MDGs, and highlighting potential changes required at WHO to ensure a leading role for health in the new SDG framework. As the lead United Nations agency on health, how effectively WHO can continue to advocate for the role of health in achieving the broader SDGs will shape the global health landscape. GHTC has been tracking progress on the SDG monitoring framework and proposed specific indicators to measure global health R&D in our report, “ Measuring Global Health R&D for the Post-2015 Development Agenda.” GHTC also produced a factsheet and a webinar on innovation in the SDGs. Agenda item #8 – Preparedness, surveillance and response – Wednesday, January 27 8.5 – Global action plan on antimicrobial resistance – Update to the Board Following on two previous World Health Assembly (WHA) resolutions on antimicrobial resistance, the Secretariat will propose either a summit at the opening of the 2016 General Assembly or a high-level side event on the margins of the same. Given the dramatic rise in antimicrobial resistance globally, WHO hopes to use this high-level event to mobilize global support and resources both to develop new antibiotics and to ensure that current drugs are used appropriately. Agenda item #9 – Communicable diseases – Tuesday, January 26 9.1 – 2014 Ebola virus disease outbreak and issues raised: follow-up to the Special Session of the Executive Board on the Ebola Emergency (resolution EBSS3.R1) and the Sixty-eighth World Health Assembly (decision WHA68(10)) Unfortunately the text of this report is not yet available, stay tuned for our post-EB blog and more information! Agenda item #10 – Health systems – Thursday, January 28 10.2 – Comprehensive evaluation of the global strategy and plan of action on public health, innovation and intellectual property: progress update – Update to the Board The 2015 WHA directed the WHO Director-General to undertake an evaluation of the global strategy and plan of action on health, innovation, and intellectual property. The Secretariat will present a report outlining the work conducted so far, as well as an addendum containing key points from the evaluation inception report, including the principles that will be used in developing the full evaluation plan and design. 10.3 – Follow-up to the report of the Consultative Expert Working Group on Research and Development: Financing and Coordination – Planning for an open-ended meeting of Member States to discuss progress – Board Decision This report and decision point are two key items on the EB agenda. The CEWG on Research and Development: Financing and Coordination process continues moving forward and faces some key decisions in the coming months. At the meeting, the EB will decide if civil society will be able to participate consultative open-ended meetings scheduled for March, which will determine what resolution is put forward to the WHA. GHTC is a strong advocate for civil society’s inclusion in the process. 10.4 – Substandard/spurious/falsely-labelled/falsified/counterfeit medical products – Update to the Board The Director-General of the WHO was directed to convene a series of expert consultations on possible methods to counteract substandard as well as falsified medical products by a 2012 WHA resolution. To that end, a number of expert committees have met and produced the priority recommendation of creating a global network of focal points to tackle issues in the quality of the drug supply. These focal points would then be responsible for linking existing quality-assurance networks to a global one to ensure collaboration. Although there is no decision point in the document, work on this issue clearly continues apace. While GHTC will follow these agenda items closely, we will also keep an eye out for other late-breaking resolutions or developments and will post a follow-up blog after the EB with updates on the actual happenings! Matt Robinson in GHTC's Policy & Advocacy Officer.