Breakthroughs Blog: Malaria

As 2015 draws to a close, the Global Health Technologies Coalition is reflecting on the past year in global health innovation. Below, in no particular order, are our picks for the top global health research and development (R&D) news and stories that shaped 2015. First ever vaccine against dengue virus approved The world’s first vaccine against dengue fever was approved by the national regulatory authority of Mexico, marking an important initial step in preventing this mosquito-borne infection, which is spreading worldwide. Nearly half the world’s population now lives in dengue-endemic countries, and an estimated 390 million infections occur each year. The vaccine’s developer Sanofi spent over 20 years and US$1.65 billion developing the vaccine and is now pursuing regulatory approval in 19 other countries. Sanofi has stated it will make the vaccine available for sale at a “fair, affordable, equitable, and sustainable price.” NIH finally receives funding boost Christmas came early for the US National Institutes of Health (NIH). After years of stagnated funding, NIH—the world’s leading public funder of neglected disease R&D—will finally receive a funding boost in 2016. In the fiscal year 2016 omnibus spending package, Congress approved a $2 billion—nearly 7 percent—increase in funding for NIH from $30 billion to $32 billion. NIH has lost 22 percent of its purchasing power since 2003 due to inflation, so this boost will provide critically-needed funding for the agency to continue to build upon its record of leadership in global health R&D. Photo: PATH/Satvir Malhotra Availability of the first child-friendly, appropriately-dosed TB medicines announced Health workers will soon have a critically-needed new tool to improve treatment for the one million children infected with tuberculosis (TB) each year. In November, TB Alliance and partners announced that the first-ever appropriate, child-friendly tuberculosis (TB) medicine in the correct dose will be available in early 2016. At the moment, TB medicines are not available in appropriate doses for children, so parents must crush or cut the pills to administer. This arduous process—combined with the bitter taste—leads to poor adherence. The new treatments are strawberry- and raspberry-flavored, appropriately-dosed versions of the three most commonly used TB medicines. These new treatments are expected to significantly improve TB treatment and adherence among children. Global Health Innovation Act passes House An important new piece of global health legislation championed by GHTC—the Global Health Innovation Act—passed the US House of Representatives earlier this month. This legislation would strengthen global health R&D programming at the US Agency for International Development (USAID) by directing USAID to incorporate R&D across its global health programming and requiring the agency to report annually to Congress on its R&D programs and activities. In 2016 the hard work will begin again to get the Senate to introduce and pass companion legislation so the bill can move another step closer to becoming US law. Ebola product development advanced at lightning speed After years of slow and stunted progress in the development of drugs, vaccines, and diagnostic tools to fight Ebola, product development jumped forward by leaps and bounds in 2015. Thanks to the collaboration of developers, regulatory agencies, and the World Health Organization, six Ebola diagnostics were developed and deployed in West Africa under emergency measures, early-stage clinical trials are underway for at least two Ebola drug candidates with others in development, and at least 15 vaccine candidates are in development with two candidates undergoing Phase II/III trials. The most advanced vaccine candidate VSV-EBOV was shown to offer near-total protection, according to preliminary data analysis from the trials. While these products arrived too late to have a major impact during the epidemic, the accelerated development approaches and mechanisms used may be able to be emulated to speed product development in the future. New pediatric malaria treatment receives positive scientific opinion paving path for regulatory approval A new pediatric malaria medicine— Pyramax® Granules—will soon be available for children worldwide. In November, Pyramax® Granules received a positive scientific opinion from the European Medicines Agency (EMA) under Article 58, a mechanism which facilitates regulatory approval of the product in malaria-endemic countries. The medicine, which was developed by Medicines for Malaria Venture (MMV) in partnership with Shin Poong Pharmaceutical Co. Ltd, is a combination of two antimalarials and is designed to be easy for children to consume. It is taken in liquid form and is flavored to mask the bitter taste. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. Several promising global health products advancing through development The pipeline of global health technologies is growing and maturing with several exciting products moving through critical development stages. For example, a new medicine for drug-resistant TB became the first new TB drug to advance into clinical trials in six years when it entered Phase I trials in February, a vaginal microbicide containing a novel antiretroviral drug to prevent HIV entered Phase I trials in November, a drug candidate with the potential to become the first ever, oral-only, single-dose treatment for sleeping sickness completed Phase I trials in September, and a microbicide vaginal ring is completing Phase II trials with results expected in early 2016. Due to increased attention and investment over the last 15 years, there are now nearly 500 neglected disease product candidates in the pipeline. Global goals recognize importance of health R&D In September, global leaders ratified a new set of global goals, called the Sustainable Development Goals (SDGs), which will guide global development efforts for the next 15 years. GHTC was excited to see these goals recognize the importance of global health R&D with inclusion of a target supporting R&D of vaccines and medicines for diseases primarily affecting developing nations. It’s been broadly recognized that we cannot reach the ambitious SDG health targets—to reduce maternal and child mortality and end the epidemics of HIV/AIDS, TB, and neglected tropical diseases— by 2030 with the health technologies we have today. Now that the goals and targets are in place, accountability is key. We must ensure the SDGs translate into greater investment and political commitment from all nations to catalyze development of the next generation of health technologies needed to transform global health.

Photo credit: TB Alliance GHTC member TB Alliance announced last week the creation of the first-ever child-friendly tuberculosis (TB) medicines, which are currently undergoing regulatory review by the World Health Organization and should be available in early 2016. While TB is curable, a patient must take multiple drugs a day for six months, and existing medicines are not available in appropriate doses for children. Consequently, parents must crush or cut the pills. This arduous process—combined with the bitter taste—makes the six-month regimen difficult to follow. The new treatment is comprised of strawberry- and raspberry-flavored, child-friendly doses of the three most commonly used TB medicines. The new regimen is expected to significantly enhance adherence to treatment for the 1 million children diagnosed with TB each year. Researchers at Texas A&M University have developed a device that, when attached to a smartphone, can diagnose malaria in minutes. Using a polarized light and the phone’s camera, the device serves as a microscope. The photos taken by the device are then analyzed by a software app that diagnoses infection by counting both red blood cells and Hemozoin crystals, which are produced by the malaria parasite. The device, which is expected to cost less than US$50 and be used with cartridges costing $1 each, will be tested in Rwanda next summer. A preclinical study conducted by GHTC member Population Council in partnership with CONRAD suggests that candidate microbicide gel MZC could be even more effective against HIV than tenofovir gel, a leading microbicide candidate. Containing a potent antiretroviral, a zinc-based salt, and the compound carrageenan, the gel is intended to protect against HIV, human papillomavirus (HPV), and herpes simplex virus 2 (HSV-2). The study demonstrated that MZC was more potent than tenofovir against both HIV and HSV-2. While the study did not test the gel’s efficacy against HPV, existing research suggests that carrageenan is one of the most potent compounds against HPV. Next, MZC will be tested in delivery systems, including vaginal rings and rectal gels, as well as in combination with a hormonal contraceptive. In other microbicide news, GHTC Member the International Partnership for Microbicides (IPM) has entered an agreement with pharmaceutical company Janssen Sciences that provides IPM the rights to develop a microbicide using the antiretroviral darunavir, which is currently available in pill form and marketed as PREZISTA®. IPM is also conducting a phase III clinical trial of a vaginal ring using antiretroviral dapirivine, licensed to the organization through a partnership with Janssen initiated in 2004.

Pyramax® Granules (Photo: MMV) After four successful Phase 3 clinical trials enrolling more than 3,500 patients in 18 countries, the European Medicines Agency (EMA) has granted Pyramax® Granules, a pediatric malaria medicine, a positive opinion under Article 58—a mechanism through which the EMA reviews and issues a scientific opinion on products that are not intended for use in Europe. Pyramax® Granules is a combination of two antimalarials and was developed by Medicines for Malaria Venture (MMV), a member of the GHTC, in partnership with Shin Poong Pharmaceutical Co. Ltd. The treatment is designed to be easy for children to consume: its bitter taste is masked and it is taken in liquid form, as children often struggle to swallow pills. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. A recent article in NPR: Goats & Soda examines Zika virus, a disease transmitted by the same mosquito vector of dengue fever and chikungunya, that has been rapidly spreading throughout South America and the Pacific Islands in recent years. One in five individuals infected with the virus experience Zika fever, which in addition to fever involves rashes, joint pain, conjunctivitis, headaches, vomiting, and muscle pain. Cases of Zika fever are likely underdiagnosed, as awareness of the disease is limited and its symptoms are similar to infections associated with other members of the Flaviviridae virus family, including dengue fever, yellow fever, West Nile, and Japanese encephalitis. There are no reported deaths to date, but there is growing evidence that the virus can be transmitted sexually or from mother to infant during pregnancy. As there are no vaccines or drugs for Zika fever, treatment involves addressing the symptoms, using fever reducers and painkillers. A group of global health advocacy organizations—including GHTC members the Drugs for Neglected Diseases initiative, TB Alliance, Infectious Diseases Society of America Center for Global Health Policy, Sabin Vaccine Institute, and Treatment Action Group—sent an open letter to the US Senate Health, Education, Labor and Pensions (HELP) committee, calling for amendments to the priority review voucher (PRV) program at the US Food and Drug Administration (FDA) to ensure it adequately incentivizes research and development (R&D) for neglected diseases, as intended. Under the program, companies that receive FDA approval for a drug for a neglected disease (see list of eligible diseases) are awarded a voucher for expedited FDA review (six months rather than ten) of a future product. The vouchers are transferable and have been sold at increasing rates, the most recent going for US$350 million. The letter calls for PRVs to only be awarded for products that are "truly new" as two of the six vouchers that have been awarded were for products that had long been in use outside of the United States.[1] The organizations are also calling for recipients of the voucher to be required to develop a strategy to ensure the product is made affordable and accessible to patients in the countries in which the eligible disease is endemic. The United Kingdom (UK) announced last week the creation of the Ross Fund which will provide £1 billion ($1.5 billion) over five years to fight malaria and other infectious diseases. The funding, which will come from the UK overseas aid budget, includes £90 million for malaria eradication; £100 million for infectious disease R&D; £115 million for the development of drugs, diagnostic, and insecticides for malaria, tuberculosis, and other infectious disease resistance; and £188 million for biodefense and rapid response systems for epidemic preparedness. Global Good has developed a cooler that can store and transport vaccines at freezing temperatures for over a month using just ice and no electricity. The Arktek cooler uses vacuum thermal insulation, an approach used to preserve spacecraft entering extreme temperatures. The cooler has been tested in Senegal (with support from GHTC member PATH) and Ethiopia, and last year, the Arktek was modified for use in Ebola vaccine clinical trials, during which the cooler kept the vaccines between -76 and -112 degrees Fahrenheit for three days. [1] There are two separate PRV programs at the FDA, one for neglected tropical diseases and one for rare pediatric diseases. Of the six PRVs that have been awarded, three each have been for neglected tropical diseases and rare pediatric diseases. Since the beginning of the PRV program, six PRVs have been awarded—three for neglected tropical diseases and three for rare pediatric diseases.  

Photo: National Institute of Allergy and Infectious Diseases (NIAID) Researchers at Tulane University successfully tested an experimental aerosol tuberculosis (TB) vaccine in monkeys, demonstrating that the candidate was more effective in protecting against infection than BCG—the only TB vaccine on the market. To create the vaccine, the researchers genetically modified the TB bacterium, removing a gene that plays a key role in infection. The vaccine was then administered to seven monkeys, while another seven each received either an aerosol version of BCG or no vaccine. After eight weeks, the monkeys were exposed to TB at a lethal level. The experimental vaccine not only was more protective than BCG, but it also induced a stronger immune response in the lungs, which is thought to be key to preventing infection. A new formulation and coating for existing HIV and AIDS medicines could significantly decrease the frequency with which the drugs must be taken. Researchers at the University of Nebraska Medical Center used a process called nanoformulation, which involves modifying drugs at the most basic level (i.e., atomic or molecular level) in order to convert them into nanoparticle crystals. In this experiment, the antiretroviral medicine crystals were coated with fat and protein, allowing them to last much longer in the body. In the lab, the drug proved to be effective in combatting HIV and AIDS. The team hopes its findings could eventually lead to the development of an HIV and AIDS treatment that could be administered once or twice per year, rather than daily. Resistance to the leading antimalarial—artemisinin—was first reported in Cambodia in 2008, and a new study in Nature Communications suggests that the drug-resistant parasite has the ability to infect African mosquito species. A team of researchers at the US National Institute of Allergy and Infectious Disease infected two Asian and one African mosquito species with the drug-resistant malaria parasite, and all three species proved to be susceptible. Furthermore, the African species were no less vulnerable to infection, which came as quite a surprise as the species have evolved independently for more than 30 million years. Health officials from the United States and Saudi Arabia are considering a collaboration for the development of a vaccine against Middle East Respiratory Syndrome (MERS), which has infected more than 1,500 people across 27 countries. There are currently a number of MERS vaccines in development and several have yielded promising results in animal studies. The Saudi Ministry of Health has US$70 million available for the project; however, the proposed role of the US government remains unknown.