Research Roundup: an aerosol vaccine for Ebola, software to enable clinical trials, an antibody against dengue fever, and more

Later this year, French pharmaceutical company Sanofi plans to launch a vaccine for dengue fever, the first on the market for an infection for which nearly half of the world’s population is at risk. Sanofi has spent more than US$1.5 billion over 20 years on the research and development (R&D) of this dengue vaccine and expects it to be not only lifesaving, but also highly profitable. Dengue fever is endemic in a number of low- and middle-income countries in Asia and Latin America and is spreading into high-income countries in southern Europe as well as Japan and the United States. In preparation for the launch, Sanofi has invested more than $300 million in a manufacturing facility for the vaccine with the capacity to produce 100 million vaccines each year. Pharmaceutical companies Takeda, Merck & Co., Inc., and GlaxoSmithKline are also developing vaccines for dengue fever, and Takeda’s candidate could be on the market by 2020. The US Food and Drug Administration (FDA) granted a Breakthrough Therapy Designation to pharmaceutical company Bristol-Myers Squibb for its HIV treatment BMS-663068, based on the results of phase 2 clinical trials. The designation expedites FDA review in order to accelerate the availability of drugs for serious or life-threatening conditions and in cases where preliminary evidence suggests that the new product would offer significant advantages over current treatments. BMS-663068 is the first antiretroviral drug that actually prevents the HIV virus from attaching to and entering human immune cells. The designation is limited to use of the drug for “treatment-experienced” HIV patients who are developing resistance to other antiretroviral treatments. A new study suggests that the appearance of a pill can impact a patient’s perception of its efficacy. The study asked more than 100 participants each from the United States, China, and Colombia to rate images of pills on anticipated bitterness, ability to fight off headaches, and how hard it is to swallow, based solely on the shape and color of the pill. Across all three countries, participants perceived white pills as the most effective, and diamond-shaped pills—in contrast to round or oval pills—as the most difficult to swallow. A majority of US participants considered green pills to be the least effective and believed that red pills would lead to greater mental alertness. Past research has also suggested that a pill’s appearance can impact use; a study from 2014 indicates that when generic manufacturers change the shape or color of a pill, nearly one-third of patients will stop using the medication. On Monday, July 20, the Center for Global Development published The White House and the World, a report with concrete policy recommendations for the next US president on everything from energy and climate to migration and trade. The report notes that the United States often serves as the “first responder” in outbreaks and is a leader in global health, but calls for clear leadership—including the appointment of a global health coordinator—and pathways for coordination across US agencies. The report highlights the needs for reform at major multilateral organizations such as the World Health Organization and suggests that the United States should spearhead reform efforts and use those platforms to advance US priorities. The report identifies ways for the United States to provide technical assistance—through an office of Global Health Trade, Economics, and Knowledge Exchange—with partners in low- and middle-income countries, ultimately calling for a shift from the “aid-based status quo” and positioning the United States as a “forward-looking and strategic investor” in global health. The Guardian took an in-depth look at the status of antimicrobial R&D, including antibiotic drug discovery, alternative treatments for drug-resistant bacteria, and improved diagnostics. In the 1950s through the 1970s, researchers were discovering around twelve new antibiotics each year just by examining soil samples and identifying compounds—generated by the one percent of micro-organisms that can grow in normal laboratory settings—that could fight off bacteria. A new device known as iChip allows scientists to cultivate microbes while still in soil, enabling them to work with the other 99 percent of micro-organisms. Researchers at Northeastern University have identified 25 potential compounds using iChip, including one that demonstrates promise against drug-resistant tuberculosis and that the team believes could be available for use in humans within five years. According to Dr. Kim Lewis, the project’s lead researcher, “the rule of thumb is you need 50 promising leads for one drug, [so] we will keep searching for more.” Dr. Matt Cooper, a professor of chemistry at the University of Queensland, is also searching for new antimicrobial compounds. Earlier this year, he established the Community for Open Antimicrobial Drug Discovery, which will collect thousands of chemicals and test them for antibiotic potential. While Lewis and Cooper search for new compounds, others look for alternative or supplemental treatments for drug-resistant bacteria. The London-based biotech company Helperby Therapeutics has developed a “resistance breaker,” which Chief Scientific Officer Anthony Coates describes as “punching holes in the membrane of bacteria” to enhance the ability of existing antibiotics to combat the bacteria. David Livermore, a professor of medical microbiology at the University of East Anglia, is calling for rapid diagnostics to improve the diagnosis and treatment of drug-resistant infections. Livermore compares the current use of antibiotics to “carpet bombing in the second world war,” killing off all bacteria in patients, including protective bacteria in the human gut, and leaving a vacuum in which harmful bacteria can develop resistance. Because antibiotics are cheap and used by patients for a short amount of time, however, large pharmaceutical companies can be hesitant to invest in their R&D. As Cooper explains, the “low-hanging fruit[s]” have been discovered, and government investment is now needed to return to the “golden era” of antibiotic drug discovery.

In this post, Amie Batson, MBA—chief strategy officer at GHTC member PATH—discusses a new PATH-led initiative to identify and showcase lifesaving innovations with the promise to transform global health by 2030 and offers insights into what it will take to accelerate the impact of innovation. This post originally appeared in the Innovation Countdown 2030 Report: Reimagining Global Health. What if the solutions to the greatest health challenges of our time were within reach? Imagine if the world came together around those solutions and worked to accelerate the ones with the most potential to transform health. How might the world source, assess, finance, and coordinate investment in the highest-impact innovations and dismantle the barriers that keep them from reaching the very people who need them most? This is the intriguing premise behind the PATH-led Innovation Countdown 2030 (IC2030) initiative. With support from the Norwegian Agency for Development Cooperation, the Bill & Melinda Gates Foundation, and the US Agency for International Development, we set out to identify, evaluate, and showcase health technologies and interventions with great promise to accelerate progress toward solving the world’s most urgent health issues. We turned to experts and innovators all over the globe, crowdsourcing transformative ideas and innovations that could dramatically increase the affordability, accessibility, or effectiveness of health care compared to the current standard of care. Reimagining Global Health, the inaugural report of the IC2030 initiative, features 30 innovations that experts believe could quicken the pace of progress toward the health targets in the proposed UN Sustainable Development Goals (SDGs), along with commentaries from health, technology, and business leaders. These 30 innovations are presented in four categories mapped to the proposed health targets: maternal, newborn, and child health (MNCH); infectious diseases, including malaria, HIV and AIDS, and tuberculosis (TB); reproductive health; and noncommunicable diseases (NCDs), including diabetes, cancer, and chronic respiratory and cardiovascular disease. We cast a wide net in our search because innovation is truly diverse and global. Our call for nominations brought in more than 500 ideas submitted by people in nearly 50 countries across five platforms: devices; diagnostics; drugs and therapeutics; systems and services, including digital health; and vaccines. We then tapped more than 60 health experts to evaluate and rank those innovations, selecting the final set featured here. For a detailed look at our methodology, please see pages 37–41 of the Reimagining Global Health report. Four strategies to accelerate the impact of innovation Our list of 30 promising innovations and our dialogue with experts and innovators around the world offer important insights into what it will take to harness the power of innovation to save lives. 1. Tap and support innovation wherever it occurs. Innovators are everywhere, not just in well-funded labs and technology companies in wealthy nations. Today’s innovation ecosystem is diffuse, with smart ideas coming from every corner of the globe and across every sector and discipline. The world increasingly sees the importance of user-centric solutions that are demand-driven, relevant, and affordable. The opportunities for accelerating innovation—wherever it comes from—have never been greater, empowered by digital platforms where new ideas, data, and approaches can be shared, developed, and deployed. Our crowdsourcing approach for gathering innovations is one example of the new tools that are redefining health innovation. Nearly 30 percent of the 500-plus submissions received by IC2030 came from people in low- and middle-income countries, giving voice to their growing role in health innovation. There were many more promising ideas than we could feature in this report. Strengthening the capacity of low- and middle-income countries to identify, develop, adapt, produce, regulate, assess, and share innovations is critical for a robust innovation pipeline. Investments in countries’ innovation ecosystems will catalyze better overall global health while ensuring that innovations are appropriate for low-resource markets and local contexts and cultures. Innovators with direct experience working with limited resources may be the best source for frugal innovations—cost-effective solutions to address the needs of the poor, wherever they live. 2. Assess and advance innovations that deliver the most health for the money. Rigorous and transparent assessment of an innovation’s health impact, market size, and technological feasibility compared to alternatives in the pipeline is important for informing decisions about where to invest precious health resources. Low- and middle-income country governments are requesting assistance in evaluating the potential health and economic value of introducing one innovation versus another amid a burgeoning supply of new tools and interventions. Investors are also demanding more and better data on which to base investment decisions. However, comparing innovations across diseases and conditions is a challenge. Health experts frequently focus on specific conditions and make decisions with a single health outcome in mind. A key feature of IC2030 is the health and cost impact modeling process we developed to quantify lives saved, cases of disease averted, and costs for a subset of MNCH innovations. This model could provide a common framework to assess innovations with the greatest potential to address the SDG health targets. Our impact modeling results for select maternal, newborn, and child health innovations are featured on pages 13–19 of the Reimagining Global Health report. The data provide new insights into prioritizing global health investments for greatest impact. For example, we found that new tools for community-level water treatment to prevent diarrheal disease and the scale-up of a low-cost drug to prevent newborn infections could save more lives over the next 15 years compared to other innovations we modeled. Measuring the impact of crosscutting innovations is equally important. These health systems and platform innovations, including digital tools and broad diagnostics, have the potential to address multiple SDG health targets simultaneously. About one in five of the innovations submitted to IC2030 was crosscutting in nature. Yet assessing their impact is particularly challenging because of the complexity of linking multiple health outcomes to the foundational structure of the health system that supports them. In this first year of IC2030, we did not systematically evaluate crosscutting innovations, but they will be a focus going forward. New assessment tools and more comparable, comprehensive, and reliable financial and technical data are critical to help spotlight and advance innovations with particular promise that might otherwise be overlooked. A clear and rigorous framework to gauge the best value for money in a range of low- and middle-income settings is needed to inform national and subnational purchasing decisions and the decisions of those purchasing on behalf of countries. This will also help innovation investors more accurately assess potential impact, markets, and revenue flows. Zeroing in on health solutions that offer the greatest value for money is the essential next step in reaching the millions of people still waiting to share in the gains of our progress. 3. Develop new financing mechanisms for global health innovation. The pool of public and private funds to invest in health innovations is large and evolving. Funds from traditional R&D and development donors—typically dedicated public funds from wealthy countries—are being augmented by resources from philanthropies, social impact investors, private-sector mechanisms, and domestic sources. This new mix of innovation funding creates both opportunities and challenges. Domestic funding to introduce and scale up health innovations is becoming central to innovation funding. As low- and middle-income economies grow and countries graduate from aid, they are expected to finance their own health expenditures, creating new markets for affordable health tools and interventions. Sustainable financing of innovation will depend on the decisions of domestic stakeholders, including governments, insurance entities, corporations, and individuals. As more viable markets emerge, we will see a rebalancing of innovation from being primarily supply-side driven by donors and the R&D community to being more demand-side driven by countries and markets. Supporting country decision-makers to buy or, in the case of insurance mechanisms, cover or reimburse cost-effective health innovations must be at the heart of a new and improved financing model. Global funding mechanisms, including the Global Fund to Fight AIDS, Tuberculosis and Malaria and the new Global Financing Facility at the World Bank, may be well-positioned to act as intermediaries, as Gavi, the Vaccine Alliance, currently does for vaccines. These mechanisms can increase the certainty that funds will be readily available to purchase high-priority innovations if countries demand them. To play this role, they will need a window into the innovation pipeline and a means of engaging with eligible governments to identify high-impact innovations. The next generation of health financing mechanisms must also be responsive to the increasing requirements of social impact and private investors who base their investment decisions on not only the potential health impact of an innovation but also its probable market in low- and middle-income countries. While traditional funders have always understood the importance of having a clear “line-of-sight” to the market, it was often discounted. The assumption has been that if an innovation demonstrated significant public health value, a donor would eventually support it. New financing mechanisms must spotlight and bridge the critical links between R&D decisions, market uptake, and health impact. Innovators will respond to incentives that encourage them to maintain a focus on the market from the beginning of the development process to ensure the creation of sustainable and affordable innovations. New financing mechanisms must also provide more efficient and effective models for making and executing investment decisions. Over the past decade, the evolving spectrum of innovation funders has led to increasing fragmentation of investment decisions and growing transaction costs. Each investor—whether a public agency representative, a social impact investor, or a minister of health—brings a unique mix of risk tolerance, due diligence processes, data sources, expected returns, and interest in specific platforms, geographies, or health areas. For any investor, the difficulty and risk of investing alone is high, but today, the transaction cost of coordinating decisions and investment can be even higher. Global health investment funds try to address this challenge but require all investors to align on risk/reward preferences. The growing diversity of funders, while currently a challenge, has the potential to be a benefit if investors can leverage their different interests and risk tolerance. If actively coordinated, mixed sources of funding can be structured to finance different stages in the innovation cycle with a focus on the market. This means recognizing the growing role of purchasers in establishing a market, as well as finding new ways to align the decisions of investors and purchasers. All parties would make better decisions if they knew, and could count on, what others were doing. 4. Coordinate investments to ensure a strategic approach to health innovation. Coordinated investments in innovations across the continuum of care, including prevention, diagnosis, treatment, and disease management, have the potential to ensure a comprehensive suite of health tools and services designed for the greatest possible impact. The proposed SDGs provide the opportunity for investors to work toward shared health targets and better coordination in how they source, assess, and invest in innovations that achieve those targets. Yet we found potential inefficiencies in investment approaches that may underscore the current lack of coordination. In certain health areas, for example, we received nominations for multiple devices all taking a similar approach to address the same health condition. While competition might result in better tools at better prices, it also raises the question of whether donors are aware of what others are investing in and whether scarce resources could be more strategically targeted. In maternal health, we received many submissions for diagnostics to predict and detect preeclampsia/eclampsia—the second leading cause of maternal mortality—but few innovations for the treatment of these life-threatening conditions. In many low-resource settings, the existing treatment, magnesium sulfate, is underused, incorrectly administered, or unavailable. Diagnostics will have limited value unless innovations in new treatments and delivery systems are developed in parallel. A broader understanding of where investments in innovation are high—or very low—is also warranted. NCDs now account for about two-thirds of global deaths, yet we received very few innovation nominations. Donors may assume others are funding NCD innovations while they focus on infectious diseases. Will they be surprised when they pivot to NCDs and discover the lack of appropriate innovations for people in low-resource settings? Could investments in preventive innovations today allow countries to effectively leapfrog developed nations and avoid creating the huge treatment burdens associated with NCDs? Conclusion The robust and growing innovation pipeline presents an exciting opportunity to accelerate high-impact solutions that can create better health and opportunity for all. Ensuring the best ideas are surfaced—wherever they come from—is the first critical step we must take to deliver on the promise of the SDG health targets. This should include investing in the innovation ecosystem in low-resource countries to enable local entrepreneurs to develop, produce, and share their ideas. It also means using new crowdsourcing tools to gather ideas and data visualization to make the comprehensive pipeline more visible to national and global investors, policymakers, and innovators. Developing and adopting assessment methodologies that provide common, consistent, and comparable evaluations of innovations is the second step. Countries are in great need of health technology assessment tools that allow governments and insurance entities to decide which of the many innovations available today and in the future should be procured, covered, and reimbursed. These tools also will improve the quality of market estimates, one of the most critical and yet weakest components of innovation assessment for all investors. The third step is to develop innovative financing mechanisms that both recognize the growing importance of domestic finance in determining markets in low- and middle-income countries and benefit from the growing diversity of investors. Financiers have the potential to leverage their investments by aligning with other funders while maintaining a strategic focus on the market. Aligned investment across the different stages of the innovation cycle, from development to production, commercialization, purchase, and wide-scale use, has the potential to dramatically accelerate our progress. The fourth step may be the most essential—coordinating the resources and attention of investors, innovators, and policymakers on innovations with the greatest potential value for money. Our progress depends on decision-makers sharing information to ensure that collectively, the world is investing in the portfolio of innovations that will allow us to achieve our shared goals embodied in the SDGs. Innovation is the key to sustainable health impact. But innovation isn’t a random set of ideas and inventions. High-impact innovation is more likely to result from the kind of sourcing, assessment, financing, and coordination described above. It is our hope that one or more of the innovations highlighted in this report will become a game-changer for global health over the next 15 years. But beyond the success of any single innovation, we hope IC2030 will be a platform to catalyze discussion, collaboration, investment, and momentum toward the day when everyone has an equal chance for a healthy life. Photo: PATH/Gabe Bienczycki.