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WHO EB meets. Photo: GHTC/Jana Armstrong Over 1,000 attendees, a longer than ever agenda—with time management by a song for punishment and a chocolate Caramello Koala as a reward—the 138th World Health Organization (WHO) Executive Board (EB), chaired with humor and efficiency by Precious Matsoso, Director-General of the Department of Health, South Africa, concluded Saturday, January 30 after six days of discussion and debate. The main headlines were WHO emergency reform, WHO reform in general, the Zika response, transitioning from the Millennium Development Goals to the Sustainable Development Goals, universal healthcare, preparation for the United Nations (UN) High-Level Meeting on noncommunicable diseases, the upcoming UN General Assembly Special Session on the World Drug Problem, Framework for Engagement with Non-state Actors, Global Action Plan on Strategies for antimicrobial resistance (AMR), pandemic influenza preparedness, and promoting the health of migrants. The full agenda, associated documents and nongovernmental organization (NGO) statements can be found here. R&D featured prominently on the agenda The need for global health research and development (R&D) and access to global health technologies featured prominently in many of the agenda items addressed under Health Systems and Preparedness, Surveillance and Response including: 8.2: Pandemic influenza preparedness: sharing of influenza viruses and access to vaccines and other benefits 10.2: Comprehensive evaluation of the global strategy and plan of action on public health, innovation, and intellectual property: progress update 10.3: Follow-up to the report of the Consultative Expert Working Group on Research and Development: Financing and Coordination (CEWG), Planning for an open-ended meeting of Members States to discuss progress 10.4: Substandard/spurious/falsely-labeled/falsified/counterfeit medical products 10.5: Addressing the global shortages of medicines and the safety and accessibilities of children’s medication R&D was also embedded as an important point within some of the key headline items including: 6.4: Public health dimension of the world drug problem including the context of the Special Session of the UN General Assembly on the World Drug Problem to be held in 2016 7.2: Health in the 2030 Agenda for Sustainable Development 8.1: Implementation of the International Health Regulations discussed with 9.1 2014 Ebola virus disease outbreak: follow-up to the Special session of the EB on the Ebola Emergency: section on information sharing on diagnostic, preventive and therapeutic products 8.5: Global Plan on antimicrobial resistance 9.2: Global health sector strategies: HIV, viral hepatitis, and sexually transmitted infections 9.3: Global vaccine action plan 9.4: Mycetoma The EB accepted all of these topics for inclusion in the 69th World Health Assembly (WHA) agenda. A number of NGOs, including GHTC, weighed in on R&D and access related topics discussed at the EB meeting. Full NGO statements delivered at the meeting are available here. Three resolutions related to health R&D introduced for WHA Most of the EB agenda consisted of “recognizing reports,” “providing guidance,” and “reviewing draft strategies,” however, the EB decided to put forward three resolutions for consideration at the WHA in May that have clauses related to R&D: Draft resolution on Health in the 2030 Agenda for Sustainable Development Draft resolution addressing the burden of mycetoma Draft resolution promoting the safety and accessibility of children's medicines Small steps taken on CEWG Agenda item 10.3, follow-up of the report of the CEWG, was particularly important for GHTC and other health R&D advocates. The EB discussed progress on the process and set the agenda for an open-ended meeting on the topic that will take place in March. This meeting is expected to result in a WHA resolution on possible WHO mechanisms for global health R&D priority setting, coordination, and a pooled fund for R&D. During the discussion, member states and observers made the following interventions: All member states supported the Global Observatory on Health Research and Development, a WHO platform created by the CEWG process to collate information on health R&D activities globally to identify gaps and opportunities and define priority areas for new R&D investments. Many statements expressed disappointment that funds received to support R&D (US$10 million) are dramatically lower than funding pledges ($85 million). Statements were made calling for the new pooled fund to incorporate support for R&D on antimicrobial resistance and emerging infectious diseases, though there was not consensus on this point. Several participants questioned how the CEWG process is coordinating with the UN Secretary-General’s (UNSG) High-Level Panel on Access to Medicines. The assembly seemed unified on non-state actors being allowed to attend the open-ended meeting, while holding open the possibility of a closed session on financing and coordination of next steps. Many participants argued for the need to de-link R&D costs from product price to increase affordable access. It was acknowledged that the fund should de-risk investment for low- and middle-income countries. Participants recognized a need to interface between work streams—observatory, priority setting and coordination, and the pooled fund. Feedback was given on the demonstration projects chosen and not chosen. P. Sharma of India was nominated by consensus as the chair of the open-ended meeting. The following NGOs made statements on this agenda point: GHTC (delivered through Global Health Council) Drugs for Neglected Diseases initiative Médecins Sans Frontières International Medicines for Malaria Venture Medicus Mundi International Organization for Cooperation in Health Care GHTC’s statement requested that global health R&D NGOs be permitted to participate in the March open-ended meeting since product development partnerships and public-private partnerships are responsible for 58 percent of the product candidates currently in the pipeline. The decision was ultimately made to include civil society. In wrapping up this agenda item discussion, Marie-Paule Kieny, WHO Assistant Director-General of Health Systems and Innovation, thanked Member States for their constructive requests and described this process as a marathon, not a sprint. She also highlighted the financial gap facing the current demonstration projects. Regarding the agenda of the open-ended meeting, she said that comments would be taken into consideration and proposed the following revised agenda: Day 1: Progress on strategic work plan and report from the UNSG High-Level Panel on Access to Medicines. Day 2: Presentations of work relevant to the CEWG: neglected tropical diseases; the global action plan for AMR; R&D Blueprint for action to prevent health epidemics; World Intellectual Property Organization (WIPO) research; and trilateral cooperation between WHO, the World Trade Organization, and WIPO on health, innovation, and access. Member state and Non-State actor statements. Day 3: Financing and Coordination. Looking forward, the 69th WHA agenda will very closely resemble the agenda of this 138th EB since the main point of the January EB meeting is to set the agenda for the WHA. Therefore, it will include important R&D topics including outcomes from the March open-ended meeting, the resolution votes, and the strategic plans discussed at this EB.

Euvichol® produced by EuBiologics. Photo: IVI In January, GHTC member International Vaccine Institute (IVI) announced that a new oral cholera vaccine it developed in partnership with Korean biotech company EuBiologics, Co. Ltd.—Euvichol®—received prequalification from the World Health Organization (WHO), paving the way for the vaccine to be purchased by global procurement bodies like Gavi, the Vaccine Alliance and UNICEF. GHTC’s Breakthrough blog is joined by Jerome Kim, IVI’s Director General, to learn more about this exciting development which will ease global supply limitations of the oral cholera vaccine and expand affordable access in countries where the disease is endemic. Tell us why this breakthrough is so critical. Cholera is a potentially fatal diarrheal diseases that affects between 1.4 million and 4.3 million people each year and causes as many as 142,000 deaths annually in low-income countries. Cholera is endemic in more than 50 countries, with outbreaks often occurring during humanitarian or natural disasters. Oral vaccines against cholera have existed since the 1990s as a potential tool to stem outbreaks. However, because the disease primarily affects poor communities there wasn’t a stable market to create demand for vaccine production at an affordable cost for these countries. To create a stable market for the vaccine, WHO created an oral cholera vaccine stockpile in 2013 to make the vaccine available at an affordable price for vaccinations in epidemic situations and endemic countries. In recent years, increasing demand for the vaccine created supply pressures on the stockpile and limited more extensive implementation of the vaccine. The prequalification of Euvichol® by WHO means a third oral cholera vaccine producer has entered the market. This will significantly increase the number of oral cholera vaccines doses available worldwide and address global shortages. Euvichol® is also expected to help bring down costs and expand access. How did the vaccine come to be developed and prequalified? The prequalification of Euvichol® is the culmination of a five-year long partnership between IVI and Eubiologics, a Korean biotech company. IVI worked with partners in Vietnam, Sweden, India, and the United States to develop a reformulated oral cholera vaccine to meet the needs of low-income countries. IVI originally transferred the technology to an Indian biotechnology company Shantha Biotechnics. Shantha licensed the vaccine in India under the name Shanchol™ in 2009 and received WHO prequalification for the product in 2011. To strengthen the cholera vaccine market further, in 2010, IVI transferred the technology for the vaccine to Eubiologics, as a second producer and manufacturer. Eubiologics advanced the product through clinical trials, receiving licensure from the Korean Ministry of Food and Safety in January 2015. This paved the way for the product to receive WHO prequalification in December, 2015. The development of Euvichol® was supported by the Bill & Melinda Gates Foundation, the Republic of Korea, and Sweden. The Global Health Investment Fund (an impact investment fund sponsored by the Gates Foundation and other partners), Korea-Seoul Life Science Fund, Korea Investment Global Frontier Fund, and Green Cross Corporation also provided funding to Eubiologics. The creation of Euvichol® is a great example of how the contributions of public, nonprofit, and commercial partners can be leveraged to advance technology development for diseases impacting the poor. What’s next for the vaccine? EuBiologics has initiated production of 6 million doses of the vaccine for 2016, which is expected to double WHO’s stockpile. IVI will continue to work with the WHO and partners to promote uptake of the vaccine and make sure it is available and used in places where it is needed most.

Photo: CDC Vaccines The US National Institutes of Health (NIH) is ramping up research for a vaccine against Zika, a mosquito-borne virus which is “spreading explosively” throughout the Americas and can cause birth defects, including microcephaly, which is associated with stunted head and brain development in newborns. The NIH will be offering new funding for Zika research and supplementary funding will be available for researchers studying similar viruses, including West Nile, dengue, and yellow fever. The NIH plans to initiate clinical trials of a Zika vaccine by the end of this year, and currently has two potential candidates, one resulting from research into West Nile virus. The Brazilian government is also supporting Zika vaccine research and development (R&D), but despite its commitment to developing a vaccine “in record time,” the process will take at least three to five years. GlaxoSmithKline is conducting feasibility studies to determine if its existing vaccine technology could be used to develop a Zika vaccine, however, the company warns it could take ten to fifteen years. Inovio Pharmaceuticals and GeneOne Life Science are initiating research to develop and test a DNA-based Zika vaccine, building on their current partnership for Ebola and MERS vaccine R&D. Treatment There are currently no available therapies for Zika disease and the US Centers for Disease Control advises treating the symptoms by resting, hydrating, and taking medicines for the fever and pain. The National Institute of Allergy and Infectious Diseases (NIAID) at NIH is testing Zika drug candidates. In light of the paucity of treatment options, NIAID Director Dr. Anthony Fauci is calling for a shift in the drug development “one-bug–one-drug approach,” noting that recent pandemics have demonstrated the need for antivirals effective against entire classes of viruses. Diagnostics Point-of-care diagnostics are “the first line of defense in these outbreaks,” according to FIND Chairman Mark Kessel, as rapid, accurate diagnosis is needed to “identify, treat and track the outbreaks to minimize the deaths and costs to the world economy.” Currently, the standard approach for diagnosing Zika takes place in laboratory settings, and involves looking for the virus’ RNA in a blood sample, however the RNA only remains in the blood for a short period of time, and by the time the symptoms begin (3 to 12 days after infection), it may be too late. As exposure to Zika virus during pregnancy can lead to birth defects, scientists are also interested in diagnostic approaches that can test for past infections in newborns, however the leading method requires access to the live virus and advanced safety conditions not found in most labs. When testing for antibodies against the virus in blood samples, differentiating between related viruses can be difficult, and Zika is primarily found in areas in which the related dengue virus is endemic. Despite these limitations, several diagnostics that test for antibodies against Zika are already on the market. Most notably, the Canadian diagnostic company Biocan launched a rapid Zika test in December that takes just ten minutes, and uses a finger prick to collect blood, making it safe for use in the field. Biocan is also launching the Tell Me Fast Dengue/Chikungunya/Zika Virus Combo Rapid Test, which as the name suggests, can detect dengue, chikungunya, or Zika virus. Researchers at the University of Texas are developing a “cheap, portable box” that detects Zika virus DNA. The team has developed a prototype and is seeking additional funding for continued development and testing. The box structure enables testing of mosquitos for Zika virus, and could allow scientists to detect an outbreak early, rather than relying on reported cases in humans. Vector Control Without approved vaccines or drugs, and limited point-of-care diagnostic options for Zika virus, public health officials are calling for heightened mosquito control efforts. British biotechnology company Oxitec is testing genetically modified mosquitos to reduce the population of the Aedes aegypti mosquitos which transmits Zika, as well as dengue and chikungunya. Oxitec’s mosquitos are engineered to produce larvae that are unable to mature to adulthood, and in an ongoing trial in Piraciaba, Brazil, the introduction of the engineered mosquitos has resulted in an 82 percent decrease in A. aegypti larvae in just nine months. In response to the Zika outbreak, Oxitec is expanding its trial and building a new facility to produce the mosquitos. Oxitec is currently seeking approval from the US Food and Drug Administration to conduct additional trials in the Florida Keys. The US government is taking the spread of Zika seriously, and President Barack Obama has called for research into Zika vaccines, drugs, and diagnostics. However, the White House is also emphasizing that the threat from Zika is distinct from that of Ebola. While the risk to women who are or may become pregnant is significant, for others, “the impact of the virus is relatively mild." Are there additional Zika R&D initiatives that we’ve missed? Please send tips to Kat Kelley (kkelley@ghtcoalition.org).

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.