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There is a safe, affordable, single-dose vaccine that protects against yellow fever for 99 percent of those vaccinated, yet a recent outbreak of the disease has resulted in nearly 2,000 cases and killed 258 in Angola. Yellow fever is endemic in 44 countries, including Angola, and the global demand for the vaccine surpasses availability by 42 percent. Additionally, the cost of the vaccine has increased 30 percent annually. The vaccine is currently produced by four manufacturers, and its production is complicated, requiring embryos in chicken eggs. A vaccine with an inactivated version of the virus, which would be much easier to manufacture, has successfully completed phase 1 clinical trials, however, it has not yet been commercialized. As the World Health Organization is leading negotiations to divert yellow fever vaccines from routine immunization programs to Angola, the existing vaccine could also be delivered in smaller quantities to more people: just one-fifth of the standard dose has proven to be effective against the virus. A team of American and German scientists have demonstrated that an injection with potent anti-HIV antibodies can protect against the virus in monkeys for nearly six months. The researchers used four different antibodies that have proven to be effective against various HIV strains and administered one type each to four different groups of monkeys. The monkeys were then exposed to the virus on a weekly basis. On average, the monkeys were protected for 12 to 14 weeks, although some were protected for up to 23 weeks. Previous studies have shown that antibodies can provide short-term protection against HIV in monkeys, however, in most studies, the monkeys were exposed to the virus in one high-dose shot. In reality, most infections in humans develop gradually as a result of repeated, low-dose exposures, and thus, this study sought to emulate standard human transmission. Currently, the first-ever clinical trial of a single antibody is being tested in individuals at high-risk for HIV infection, however, it’s expected that a cocktail of these potent antibodies would be even more effective at preventing infection.  New research out of Florida Gulf Coast University indicates that previous infection with dengue virus could exacerbate symptoms from the Zika virus. This phenomenon—antibody-dependent enhancement, in which the presence of protective antibodies against one disease increases vulnerability to another—has been reported among different strains of dengue virus. The team at Florida Gulf Coast University confirmed that in cell cultures, the presence of antibodies against dengue intensified Zika infection, however the research also suggests that a single vaccine candidate could be effective against both diseases. These findings, coupled with the shared Aedes aegypti mosquito vector, indicate that the spread of Zika in dengue-endemic regions could be more virulent than expected. 

This post is part of the #MarketsMatter expert blog series. Read the full series here. The size, strength, and stability of markets dictate how health product developers set priorities and fund research and development (R&D); a 1 percent increase in the potential market size for a drug category leads to a 6 percent increase in the number of medicines introduced in the US market.[i] However, relying on market forces alone to drive health R&D leads to staggering disparities in funding and real-world impact. Today, only 1 to 2 percent of all global investment in health R&D targets neglected diseases, which kill more than 6 million people each year and disproportionately affect low- and middle-income countries (LMICs).US Navy Lt. Kimberly Edgel, left, and Christian Baldeviano examine a positive malaria blood smear at Naval Medical Research Unit (NAMRU) 6 in Callao, Peru. When existing market forces alone fall short in ensuring availability of and access to lifesaving health tools, a range of interventions are needed to alter the market and ultimately change the behavior of its actors. Incentives and innovative financing mechanisms are interventions that have proven effective in accelerating R&D and delivering lifesaving vaccines, drugs, diagnostics, and other health tools to those who need them most. Incentives such as advance market commitments (AMCs), volume guarantees, milestone prizes, and priority review vouchers reward developers who conduct neglected disease R&D or guarantee a market for a health product, ensuring that developers are able to recoup the costs of R&D. Innovative financing mechanisms, including mix-method financing, cross-sector partnerships, pooled funding, and competitions directly subsidize and consequently catalyze R&D. These platforms and partnerships are already accelerating R&D and promoting access to new innovations. AMCs—agreements by procurers to purchase a specified quantity of a new product at a predetermined price, effectively securing a market for product developers—have moved from innovative idea to reality over the past decade. In 2007, Gavi, the Vaccine Alliance launched an AMC for pneumococcal vaccines, raising US$1.5 billion from six public and philanthropic donors to purchase a future vaccine. While there were already two late-stage candidates in the pipeline that met the AMC’s criteria, the commitment created competition and encouraged GlaxoSmithKline (GSK) and Pfizer to adapt the vaccine candidates for low-resource settings. The AMC also stimulated demand; the vaccine has been introduced in more than 50 LMICs, and both GSK and Pfizer scaled up manufacturing to meet the demand, reporting that these decisions were influenced by the existence of the AMC. Earlier this year, Gavi initiated a similar agreement, signing an advance purchase commitment with Merck, providing $5 million toward the development of an Ebola vaccine. Merck guaranteed that the product would be submitted for licensure by the end of 2017, and 300,000 doses would be made available by May 2016 for use in either a future outbreak or clinical trial. Not only has Ebola historically affected LMICs, but the disease typically emerges in short-term outbreaks, and thus, the market is limited and unstable. This agreement will ensure that a stockpile of vaccines are ready to be deployed during the next outbreak and signals to vaccine developers and manufacturers that cross-sector partnerships can offer a market for emerging and reemerging infectious diseases. While incentive mechanisms can expedite product development and access to new health tools by creating market demand and new financial incentives, innovative financing mechanisms that directly fund R&D remain critical and have played a tremendous role in bolstering the neglected disease pipeline. The pipeline has grown from 365 products in 2012 to 485 tools today, three-fourths of which are being developed by public-private partnerships, including product development partnerships, which facilitate collaboration across the public, private, and philanthropic sectors, bringing in new resources and diverse expertise. Other innovative financing mechanisms include pooled funds, such as the Global Health Innovative Technology (GHIT) Fund, which is financed by the Japanese government, seven Japanese pharmaceutical companies, and the Bill & Melinda Gates Foundation. The GHIT Fund has brought new investors and resources to the table and is currently supporting nearly 50 drug, vaccine, and diagnostic candidates. Alternately, Grand Challenge programs offer a platform for open innovation, identifying and financing promising ideas to address health and development challenges. Through its Grand Challenges series, the US Agency for International Development has elicited 7,400 ideas and has supported 224 of them, leveraging $125 million in new funding to match the agency’s investment of $76 million. Markets for neglected disease products are often perceived as insufficient to warrant investments in R&D, and thus, we can’t rely on existing market forces alone to determine R&D funding and priorities. An enabling policy environment, cross-sector partnerships, and innovative financing mechanisms have a critical role to play in galvanizing greater industry engagement and addressing the market failures that inhibit neglected diseases R&D.The Global Health Technologies Coalition (GHTC) works to save and improve lives by encouraging the research and development of essential health technologies. We are a coalition of more than 25 nonprofit organizations advancing policies to accelerate the creation of new drugs, vaccines, diagnostics, and other health tools that bring healthy lives within reach for all people. GHTC is housed at PATH and funded in part by the Bill & Melinda Gates Foundation. Learn more at www.ghtcoalition.org. [i] According to the authors of this study, the correlation between market size and new drugs entering the market likely applies beyond the US market, but this data is not readily available. However, the US market has a disproportionate impact on R&D funding and priorities, as it constitutes an estimated 40 percent of the global market. For more information, see the study, published in The Quarterly Journal of Economics, here.

On Tuesday, GHTC launched our seventh annual policy report through a congressional briefing and panel discussion. The critical role played by the US government in catalyzing global health research and development (R&D) was a recurring theme, as panelists discussed the interconnectedness of global and American health and emphasized the need for new health tools to protect against outbreaks and continue progress. As moderator, GHTC Director Erin Will Morton opened the briefing, reminding attendees that despite the landmark progress achieved in global health over the past fifteen years, the US government must continue to invest in health R&D to achieve the next milestones in global health. “Goal setting works. And R&D for new technologies is key to achieving global health goals,” said Morton. Morton emphasized how past investments have had a remarkable impact, highlighting that the neglected disease pipeline has grown from 365 products under development in 2012 to 485 in 2015. However, as the GHTC policy report points out, US funding for global health R&D has stagnated or declined since 2009, and with the exception of the emergency funding for Ebola, 2014 funding levels were down 13 percent. “Our dollars are best spent when [US] agencies are working closely together,” said Morton, highlighting three goals the US government should embrace to advance innovation, as detailed in the report, including the importance of sustainable, long-term funding and innovative financing mechanisms; improved coordination of global health R&D efforts across US agencies; and streamlined and strengthened regulatory pathways. Panelist Dr. Peter Hotez—president of the Sabin Vaccine Institute and US science envoy—reiterated the need for long-term, sustainable funding for global health R&D, noting that the science to develop an Ebola vaccine was first published in 2013, but the technology sat there and was not advanced to product development because Ebola is a neglected disease and the technology offered little financial incentive to the private sector. He emphasized the role of US government investment in catalyzing health research, noting that when the US government “stepped in” and put up more than US$100 million to develop an Ebola vaccine, three leading pharmaceutical companies joined in. Dr. Hotez called for new actors, partnerships, and innovative models to advance R&D, lamenting that “our technical ability to make these innovations has outpaced our social, political, and financial instruments.” Further, Dr. Hotez challenged the notion that neglected tropical diseases (NTDs) are restricted to low- and middle-income countries, noting that 70 percent of NTD cases occur in G20 countries and that “there are 12 million Americans living in poverty with a neglected disease,” adding that neglected diseases are common but are “mostly striking the poor, mostly people of color, more in the American South.” Ambassador Jimmy Kolker discusses how HHS work contributes to both helping individuals overseas and protecting the health of Americans. (Photo: GHTC/Marissa Chmiola)The other panelists concurred, echoing that global health is American health. Panelist Dr. Patrick Kachur—principal deputy director of the Center for Global Health at the US Centers for Disease Control and Prevention (CDC)—made clear that CDC’s global health work is grounded in the agency’s responsibility to protect Americans. Ambassador Jimmy Kolker, assistant secretary for Global Affairs at the US Department of Health and Human Services (HHS), added that “over the next 50 years, the cost of lives and money to the global system of the threat of terrorism, climate change, and epidemics is in the same ballpark,” however, noting that what the US government is investing in fighting terrorism and climate change “so far outstrips what we’re doing in terms of outbreaks and epidemics.” Dr. Kachur called for enhanced coordination, stating “R&D is a whole-of-government and cross-sector affair.” Panelist Dr. David Shoultz—global program leader for Drug Development and Devices and Tools at PATH—furthered this point, noting that “innovation takes place within an enabling ecosystem, and in our context, that enabling ecosystem involves the NIH [National Institutes of Health], the FDA [Food and Drug Administration], HHS, the CDC, our close colleagues and friends at other product development partnerships, and private-sector participants.”In closing, Ambassador Kolker argued that the US government must continue to invest in R&D and consider “how the public sector can be the enabler of the private sector,” both to develop new health tools and to ensure the United States keeps its “competitive edge” as a leader in science and innovation. Dr. Shoultz agreed, stating that “US leadership [in global health] has mattered, it continues to matter, it will matter” in an increasingly globalized world and that investing in health research and innovation is “enlightened self-interest.”To watch the entire discussion, see below: