Directions in Global Health (Volume 10, Issue 1)

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DIRECTIONS May 2013 Volume 10, Issue 1 IN GLOBAL HEALTH New source of key drug for malaria treatments Innovative approach to producing artemisinin promises better care for women, children, and other vulnerable groups

A public-private partnership led by OneWorld Health, PATH’s drug development program, has pioneered an innovative method to manufacture artemisinin, a key ingredient for recommended malaria treatments. The recent launch of industrial- scale production will help to extend effective therapy to millions more people—including pregnant women and young children, who are most vulnerable. Up to now, the leaves of the sweet wormwood plant have been the world’s only source of artemisinin. The new approach uses genetically engineered yeast to produce artemisinic acid and then novel chemistry techniques to convert this into semisynthetic artemisinin. The unpredictable cost and volatile supply of plant-based artemisinin has put artemisinin- based combination therapies (ACTs) out of reach for many people most at risk. By

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Sharing PATH’s perspective: Ponni Subbiah on collaboration to expand availability of malaria treatments work with global page 2 » health colleagues New cervical cancer Protecting infants in brief screening test hits from respiratory page 7 » news and the market syncytial virus notes page 3 » page 6 » page 8 » Perspective Cross-sector collaboration to expand objectives that kept us focused on our common mission—to use the latest technology and innovation the availability of malaria treatments to work toward malaria eradication. While teaching and providing care at Mulago From the technology that provided the foundation for Hospital in Kampala, Uganda, I saw many patients the project—genetically engineered yeast to produce with malaria. My experience in Uganda helped me artemisinic acid—to the novel photochemistry appreciate the importance of ensuring that malaria process to convert artemisinic acid to semisynthetic treatments reach the most vulnerable patients, artemisinin, the scientific innovation and visionary including pregnant women and young children. efforts of our partners have brought us to where we are today. It is extremely exciting to see cutting-edge Artemisinin-based combination therapies (ACTs) technology used to expand the market for much- have proved to be a safe and effective cure for needed drugs and open up new opportunities for malaria and have been recommended by the World global health impact. Over nine years, we went from an Health Organization as a first-line treatment for idea developed in a lab to industrial-scale deployment uncomplicated cases in Africa and Asia caused by the of synthetic biology techniques for drug production. Plasmodium falciparum parasite. Global demand for ACTs has skyrocketed. The number of courses of treatment Production of semisynthetic artemisinin at requested worldwide by the public sector rose from industrial scale was launched last month at a 11 million in 2005 to 181 million in 2010. Sanofi factory in Italy, providing the market with an additional, independent source of high-quality The world’s supply of the key ingredient of ACTs, artemisinin at stable prices. This product will artemisinin, which is derived from the sweet supplement the current plant-derived supply, wormwood plant, has not always kept pace. Rapid enabling a more steady flow of artemisinin and market growth and price and demand fluctuations greater availability of ACTs to vulnerable populations have complicated supply planning, and weather across the globe. conditions, long lead times for growing sweet wormwood, competing crops, financial concerns, The success of the partnership demonstrates and political instability have all affected production that with a shared humanitarian goal—and the and pricing. flexibility and perseverance of a dedicated team— collaboration across sectors can advance science Nine years ago, OneWorld Health (now PATH’s drug and improve global health. development program) and other organizations created an innovative public-private partnership to stabilize the artemisinin supply chain and alleviate shortages in malaria treatment. The partnership included a diverse group of experts in research, pharmaceutical product development, and public health and represented the nonprofit, academic, Ponni Subbiah, MD, MPH, biotech, and pharmaceutical sectors. Recognizing directs PATH’s drug our diversity, we collaborated to establish shared development program new on path.org

Solving the mystery of missing vaccines HPV vaccine for more families www.path.org/blog/2013/03/missing-vaccines/ www.path.org/blog/2013/02/hpv-vaccine-for-more-families/ Every year, millions of doses of vaccines are lost between The GAVI Alliance has announced it will subsidize vaccine against manufacture and delivery. PATH President and CEO Steve Davis, HPV, the virus that is linked to cervical cancer, in eight countries. who recently cohosted a TED Challenge to find solutions, reveals Dr. Jacqueline Sherris, our vice president for public health impact, some of the best ideas to reduce vaccine wastage. writes about the importance of protection.

Envision a world without malaria The truth about diarrhea www.path.org/media/world-without-malaria.php www.path.org/stories/jane-wamalwa.php Malaria sickens millions every year, but we have tools to stop it. Her children’s deaths drive Jane Wamalwa to reach other parents See our new video. with lifesaving information. Read her story.

2 DIRECTIONS IN GLOBAL HEALTH New cervical cancer screening test hits the market Innovative DNA test promises to revolutionize screening and reduce death rates in low-resource settings

China’s Food and Drug PATH has advanced Administration recently approved simple, low-cost commercial use of a new rapid, screening strategies, low-cost cervical cancer screening such as visual test. Approval and sales in China, inspection of the cervix where the test is manufactured, with acetic acid, also will open the door for entering the known as VIA. This market in India in 2013 and then in technique is now being other countries. introduced or ramped up in many countries, PATH and QIAGEN, the manufac- but it is less sensitive turer, jointly developed the test, and more prone to Sellors PATH/John which is designed especially for use clinician error than The careHPV test will increase women’s access to in clinics without reliable sources newer methods of cervical cancer screening. of clean water or electricity. Called testing for HPV DNA. careHPV™, the test detects the DNA of 14 types of human papillomavirus Although most HPV We found that careHPV was used (HPV) that can cause cervical cancer. tests are expensive and require effectively even in very basic clinics Early detection and treatment of sophisticated laboratory equipment, and demonstrated better clinical precancers is essential for reducing refrigerators, and other resources performance than either VIA or deaths from cervical cancer in low- that may be lacking in developing- Pap tests. We also found that using resource settings. country settings, careHPV is careHPV with vaginal samples, self- different. The equipment fits on collected by women, gave accurate Tailoring tests to local needs a desktop and does not require results. Although some health refrigeration of reagents. Also, professionals were initially skeptical of About 275,000 women die each year results are available in less than vaginal sampling, they quickly saw its from cervical cancer. Nearly 90 percent three hours and are easy for health potential for dramatically increasing a of these deaths occur in resource- workers to interpret. clinic’s ability to screen many women. constrained settings—mainly in Africa, Asia, and Latin America—where Using field studies to advance The commercial introduction of careHPV is creating new only a small proportion of women are product use routinely screened. opportunities for countries to PATH conducted field assessments of establish or expand their cervical Although wealthy countries have careHPV in China, India, Nicaragua, cancer screening and treatment for many years used Pap tests for and Uganda. This work included programs. Widespread adoption of effective precancer screening, these exploring the potential for using the new test promises to help spare tests have not been widely used in vaginal, rather than cervical, samples millions of women from cervical low-resource settings because they for careHPV testing to eliminate the cancer over the next decade. require a network of high-quality need for a pelvic exam, which can laboratories and highly trained be difficult to arrange, costly, and staff. Also, because Pap tests miss for more information uncomfortable for women. many precancer cases, Contact Dr. Jose Jeronimo, project director, this method works at [email protected]. best when women are This work has been supported by a grant screened every couple of from the Bill & Melinda Gates Foundation. years, something many QIAGEN countries cannot afford. Read more about PATH’s work on cervical cancer at http://sites.path.org/ To reduce the burden rh/recent-reproductive-health-projects/ of cervical cancer in cervical-cancer/. developing countries, The careHPV™ device. careHPV is a trademark of QIAGEN.

MAY 2013 3 New source of key drug for malaria treatments

» continued from page 1 Several organizations provided critical expertise and intellectual property for this groundbreaking public- supplementing botanical sources, production and private partnership: distribution of semisynthetic artemisinin will lead to • The University of California, Berkeley, invented more reliable supplies of lifesaving ACTs. the technology on which the project was based: a Malaria as a major threat to maternal process that genetically altered yeast to produce artemisinic acid. and child health • Amyris, Inc., a biotechnology firm in California, Caused by parasites transmitted to people through the refined this process to enable large-scale production, bites of infected mosquitoes, malaria sickens more identified chemistry techniques to convert than 200 million people and kills about 650,000 each artemisinic acid to artemisinin, and developed a year. Among those at highest risk are the 50 million scalable manufacturing process for transfer to an women in malaria-endemic regions who become industrial partner. pregnant each year. Malaria during pregnancy can • Sanofi, a global pharmaceutical company based in cause life-threatening anemia and leads to an estimated France, provided critical improvements and scale-up 10,000 annual deaths. Maternal malaria also increases for the required fermentation process and developed the risk of spontaneous abortion, stillbirth, premature an innovative, high-yield photochemistry method to delivery, and low birth weight, contributing to as many convert artemesinic acid to artemisinin. as 200,000 infant deaths each year. • The National Research Council Canada Plant Since 2001, when the World Health Organization Biotechnology Institute provided a royalty-free license identified ACTs as the preferred treatment for most cases for needed intellectual property. of malaria, governments and other stakeholders have encouraged farmers in China, Vietnam, and elsewhere to Addressing market issues grow the sweet wormwood plant to meet rising demand for artemisinin. But bad weather conditions, competing A critical project objective was keeping manufacturing crops, and other concerns have made it difficult to costs as low as possible. This was achieved by refining the manage the supply, resulting in price volatility and biological and chemical processes for maximum efficiency. periodic shortages. For example, the project team researched several methods to maximize the yields of artemisinic acid that could be Solving technical challenges produced by genetically modified microorganisms and investigated the most efficient chemical process to convert OneWorld Health launched the Artemisinin Project artemisinic acid to artemisinin. in 2004 to create a second source of artemisinin using a no-profit, no-loss production model. The aim was to Project partners also developed a strategy for the product supplement the current plant-derived supply. launch. One concern was ensuring regulatory approval,

a decade of collaboration to bring semisynthetic artemisinin to market

2004 2008 2004 Partnered with the University Granted royalty-free license to Sanofi Received a US$42.6 million of California, Berkeley, and Amyris, Inc., to research synthetic for industrial-scale grant from the Bill & production. Melinda Gates Foundation biology techniques and develop to launch the project. fermentation process. 2007 Partnered with Sanofi for process development, manufacturing, and commercialization.

4 DIRECTIONS IN GLOBAL HEALTH which required demonstrating the equivalency of ACTs based on semisynthetic artemisinin More PATH work to address malaria and those based on plant-derived PATH is tackling malaria from all sides, with an ultimate goal of eliminating artemisinin. Also, the project team the disease. A new PATH-led project called MalariaCare, funded by the US analyzed artemisinin economics and Agency for International Development, is scaling up high-quality diagnosis market dynamics to determine how and case management services for malaria in high- to introduce the product in a way priority countries in Africa and the Mekong Region that would alleviate the global ACT of Asia. Meanwhile, the PATH Malaria Vaccine shortage and stabilize the market. Initiative is working to develop the world’s first malaria vaccine. Results of phase 3 clinical trials Status and outlook to date have shown that an advanced vaccine candidate called RTS,S, being developed with Industrial-scale production of GlaxoSmithKline, cuts cases of malaria in infants semisynthetic artemisinin was and young children by one-third and one-half, respectively. PATH is also working to provide formally launched in April at a useful information and resources to the global Sanofi factory in northern Italy. malaria community. One example is PATH’s With regulatory approval in early recent launch of a new website on malaria May, the product is now ready for control (www.makingmalariahistory.org) integration into the supply chain and a related e-newsletter. for ACTs. By providing an additional

source of high-quality product Becker PATH/Eric at stable prices, the Artemisinin Project will enable a more steady flow of artemisinin and greater availability of ACTs. that may be useful for overcoming other major global Approximately 35 metric tons of semisynthetic health challenges. artemisinin will be produced in 2013, which means approximately 70 million malaria treatments will be for more information available to women, young children, and other patients Contact Elena Pantjushenko, communications officer, who need them. at [email protected]. The project illustrates how new, highly innovative This work has been supported by a grant from the Bill & Melinda technologies can be developed through cross-sector Gates Foundation. collaboration to simultaneously advance the goals of Read more about this work at http://sites.path.org/ global health and individual partners. It provides a model drugdevelopment/. a decade of collaboration to bring semisynthetic artemisinin to market 2011 2013 Entered production phase. Launched industrial- 2008 2009 scale production Granted royalty-free Received additional 2012 at a factory in license to Sanofi funding for In partnership with Sanofi, northern Italy. for industrial-scale industrialization completed process validation, production. and commercial 2010 submitted regulatory scale-up. dossiers, and produced Completed material for testing. industrialization with the intent to commercialize therapies containing semisynthetic artemisinin.

MAY 2013 5 Protecting infants from respiratory syncytial virus PATH explores immunization of pregnant women to prevent severe disease during the baby’s first few months

Severe disease caused by respiratory • Collaborating with both Novartis Children’s Research Institute, we are syncytial virus (RSV) is a major cause Vaccines and Diagnostics and studying RSV disease burden and of hospitalization and death among GlaxoSmithKline Vaccines to the protective effect of maternal- infants and young children in develop preclinical models derived RSV antibody in infants in low-income countries. A vaccine to for evaluating RSV vaccine Bangladesh and Nepal. And with prevent infection does not yet exist. candidates for pregnant women. the University of Warwick and the This work includes both in vivo Kenya Medical Research Institute, PATH is exploring development and in vitro models. we are evaluating the relationship of a vaccine that can be given to between maternal RSV-specific pregnant women so antibodies • Working with the US National antibody titers and protection against RSV will be transferred Institute of Allergy and Infectious in infants, as well as the rate at through the placenta to their Diseases to optimize a robust new which antibody protection declines unborn children. This maternal assay format to enable scientists to after birth. immunization strategy aims to uniformly and objectively assess protect infants in the first few the amount of RSV neutralizing Work by PATH, our partners, and months of life, when a newborn’s antibody present. This will give other vaccine researchers suggests immune system is too immature for the scientific community a better that maternal immunization may direct vaccination. means to compare RSV vaccines. be a promising strategy to protect newborns against life-threatening Collaborating across sectors Assessing feasibility in low- RSV infection. This strategy has resource settings already been shown to be useful Globally, RSV causes more than for prevention of other illnesses 30 million new episodes of acute Other work streams are evaluating among infants, such as influenza lower respiratory infection each the feasibility of RSV maternal and pertussis. year and up to nearly 200,000 deaths immunization strategies in the among children under five years old. developing world. For example, PATH Ninety-nine percent of these deaths is working with researchers at Johns occur in low-resource countries. Hopkins University, Case Western for more information Contact Lauren Newhouse, communications Reserve University, and the Papua Peak hospitalization rates occur officer, at [email protected] among children from birth to five New Guinea Institute of Medical months of age. Research to assess how malaria may This work has been supported by a grant affect the transfer of RSV-specific from the Bill & Melinda Gates Foundation. Previous studies have shown that neutralizing antibody from Read more about PATH’s work giving certain vaccines to pregnant mothers to infants. With Seattle www.path.org/projects/rsv.php. women can enhance mother-to- child transmission of antibodies. To advance the development of low-cost RSV vaccines for maternal Tracking vaccine candidates immunization, PATH is partnering with vaccine developers and PATH maintains an RSV vaccine researchers from industry, academia, snapshot to track the development of specific vaccine candidates and provide and other groups. Our work includes: an overview of vaccine approaches • Partnering with Novavax, being developed worldwide. PATH Inc., on a phase 2 clinical trial regularly updates this snapshot and evaluating the company’s welcomes input from others working in RSV fusion (F) protein vaccine the RSV vaccine field. candidate in women of Download the snapshot at childbearing age in the United www.path.org/vaccineresources/ States. Results will inform efforts details.php?i=1562. to develop a vaccine suitable for use in low-resource countries.

6 DIRECTIONS IN GLOBAL HEALTH In brief

Sayana® Press pilot: injections in community locations Increasing access to and clients’ homes. family planning Between 2013 and 2016, PATH and our partners will introduce up to Worldwide, more than 200 million 12 million doses of Sayana Press women lack access to family to women in sub-Saharan Africa planning, often because they cannot and South Asia and evaluate the reach services. Sayana® Press, a product’s impact on contraceptive new formulation and presentation use, access, and service delivery costs. of an already popular injectable The data will help decision-makers contraceptive, has the potential to worldwide determine whether and complement existing forms of this how Sayana Press can support their McKern PATH/Patrick safe, reliable, and discreet method by family planning programs. providing an option that is easy to The pilot project represents a for more information administer, even outside the clinic. collaborative commitment made Contact Sara Tifft, project director, at [email protected] Pfizer’s Sayana Press uses the during the 2012 London Summit Uniject™ injection system, which on Family Planning. Partners This work has been supported in part PATH developed and licensed include the Bill & Melinda Gates by the Bill & Melinda Gates Foundation, USAID, the Frankel Family Foundation, to make injections simpler and Foundation, the US Agency for International Development (USAID), The William and Flora Hewlett safer. Uniject is essentially a small Foundation, and individual donors. bubble of plastic prefilled with the United Kingdom’s Department one dose of medicine and attached for International Development, the Read more about PATH’s work with to a single-use needle. Packaging United Nations Population Fund, Sayana Press at www.path.org/projects/ uniject-dmpa.php the contraceptive this way allows Pfizer Inc., and PATH. Country-level workers from all levels of the partners will also collaborate on Sayana Press is a registered trademark of Pfizer, Inc. health system to safely provide implementation. Uniject is a trademark of BD.

Enabling human successful methods and common programs. The guidelines will be challenges, particularly in shared widely, providing a road map milk banks to reach low-resource settings. For example, to strengthen and expand programs. more babies the process that HMBs use to Together, these efforts are helping to pasteurize milk can be expensive transform HMB systems, allowing Breast milk is the perfect food and difficult to monitor. To address them to provide safe, lifesaving for babies. It provides the energy, this challenge, PATH, the University breast milk to more vulnerable nutrients, and fluids they need, as of Washington, and the Human Milk infants worldwide. well as antibodies that help keep Banking Association of South Africa them free from illness. When a are piloting a simple, mobile phone– mother’s milk is unavailable, donated based system that guides staff for more information breast milk can be a lifesaving through pasteurization and records Contact Kiersten Israel-Ballard, senior alternative—especially for babies key information. program officer, at [email protected]. who are premature, malnourished, or Last year, PATH also convened This work has been supported by the otherwise vulnerable. University of Washington Computer HMB practitioners to leverage PATH is working to identify and Science & Engineering Department, insights and build a global technical donations to PATH’s Health Innovation implement simple, low-cost advisory group. The group discussed Portfolio, a grant from the Bill & Melinda approaches that enable human promising technologies and future Gates Foundation through the Grand milk banks (HMBs) to provide safe, priorities and helped to draft Challenges Explorations initiative, and the nourishing milk to as many babies universal best practices for safe, US National Science Foundation. as possible. effective, and sustainable banking. Read more about PATH’s support for We have assessed HMB systems It is now developing a framework human milk banking at www.path.org/ worldwide to learn more about to guide implementation of new projects/milk-banks.php.

MAY 2013 7 News and notes

PATH news

Global health leader named chief strategy officer Amie Batson, the former senior deputy assistant administrator for global health with the US Agency for International Development, joined PATH in April as our chief strategy officer. Under the newly created position, Batson helps guide PATH’s strategy, strengthens our partnerships and business relationships in the global health community, and contributes to PATH’s advocacy and policy priorities. Batson’s 20-year global health career includes positions with the World Bank, the World Health Organization (WHO), and UNICEF. Her expertise and experience “will help program notes to strengthen PATH’s role as a critical player in this field,” said PATH President Multicountry: Meningitis multicountry: Design and CEO Steve Davis. vaccine reaches 100 millionth guidelines lead to new family Read more about Amie Batson’s person, breaks cold chain barrier of water filters appointment at www.path.org/news/ Health workers in Nigeria administered Three Chinese manufacturers are selling pr121128-batson.php. the 100 millionth dose of the MenAfriVac® new, low-cost water filters based on vaccine in December, just two years after design guidelines developed by PATH. Mercury treaty protects it was introduced. PATH and WHO led the With input from low-income families vaccine access creation of the vaccine and worked with in five countries in Africa and Asia, our Government delegates have agreed to Serum Institute of India Ltd. to develop researchers designed an affordable water safeguard access to vaccines containing and manufacture it. MenAfriVac® has now filter that consumers are likely to buy and the preservative thimerosal under a reached ten countries. use to protect themselves from bacteria that cause diarrhea and other life- new global treaty on mercury. PATH The vaccine has also reached another threatening illnesses. The guidelines are coordinated a months-long advocacy milestone—regulatory approval for freely available and may help to increase effort with WHO, UNICEF, the GAVI transport and storage outside of the choices for consumers, encourage Alliance, and other global health and civil- cold chain. MenAfriVac® can be kept competitive pricing, and improve access society groups to educate United Nations unrefrigerated for up to four days, making to safe water. Environment Programme delegates on it easier to reach rural communities with the importance and safety of thimerosal. potent vaccine. Read more at www.path.org/ These efforts help protect poor countries’ news/pr121212-water-filters.php. access to the many common lifesaving Read more about the Meningitis vaccines that contain thimerosal. Vaccine Project at www.path.org/ menafrivac/index.php. Read more at www.path.org/news/ MenAfriVac is a registered trademark of Serum an130118-mercury-treaty.php. Institute of India Ltd.

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