Research Roundup: an HIV and AIDS vaccine candidate, inflatable incubator for premature babies, and US government R&D

In this guest post, Dr. Jayasree K. Iyer—Chief Scientific Officer at the Access to Medicine Foundation—writes about the findings from their newest study, which examines the current state of the vaccine pipeline and how large pharmaceutical companies are considering access to these products. Vaccine manufacturers play a critical role in innovating new vaccines and making existing vaccines more suitable for use in developing countries. Apart from developing effective, appropriate vaccines, manufacturers work with relevant stakeholders to ensure that access to these vaccines is ramped up upon market introduction, addressing issues like supply and affordability. Vaccines are the cornerstone of disease prevention: mass immunization has led to the eradication of smallpox, and between 2000 and 2010, it helped cut the global childhood mortality rate in half. Yet many people cannot access full immunization, especially with newer vaccines. Recent attempts to boost immunization coverage (e.g., of the relatively new pneumococcal and rotavirus vaccines) shows that immunization coverage and access can be increased when good vaccines, committed funding, and strong global partnerships come together. The vaccine R&D challenge The challenge with vaccine development and access is twofold: the need for new vaccines for diseases where there are no vaccines on the market (e.g., for HIV and AIDS, malaria, and for almost all neglected tropical diseases (NTDs)) and the need for vaccines that are more suitable for use in the developing world (e.g., thermostable vaccines, oral, more effective vaccines and combination vaccines). The research and development (R&D) pipeline for vaccines is primarily driven by the vaccine industry, product development partnerships (PDPs)—such as the PATH Malaria Vaccine Initiative (MVI) and Sabin Vaccine Institute—and other research institutes. With the recent outbreak of Ebola, it is clear that vaccine innovators play a crucial role in the development of safe, quality, effective vaccines, and that R&D must be stimulated by donors and regulators, as well as by market forces. Tracking vaccine development The Access to Medicine Foundation has been tracking the development and deployment of medicines and vaccines for use in developing countries since 2008. Our almost ten years of research into the world’s 20 largest research-based pharmaceutical companies has given rise to special insight into the opportunities for addressing specific challenges. These insights can be used to inform the work of other pharmaceutical companies, as well as governments, investors, donors, and market shapers. Our research prompted us to embark on the first Access to Vaccines Index (due early in 2017). While talking with vaccine stakeholders and defining appropriate, robust metrics and analysis scopes for this new access-analysis tool, we also published a preliminary report on vaccine R&D, which offers a baseline on industry efforts in this area. Data from the 2014 Access to Medicine Index was used to report on (a) the R&D pipeline for high burden vaccines and (b) the use of mechanisms that ensure rapid access and uptake of vaccines upon market approval (termed “access provisions”). Promise in the pipeline The study highlights and confirms that the vaccine R&D pipeline covers the highest burden diseases. There appears to be relatively promising candidate vaccines emerging for diseases where no vaccine yet exists on the market (e.g., for malaria and dengue). However the pipeline for these types of vaccines remains relatively empty. Considering the large development costs associated with vaccine development and the high attrition rate of vaccine R&D projects, there is little promise that other new high-need vaccines products will enter the market in the coming years. Persistent R&D gaps remain Considering the large development costs attributed with vaccine development and the high attrition rate of projects in the pipeline, there may be few vaccines entering the market in the coming years from industry. There may be other projects under development by research institutes, PDPs, and biotech companies and by other smaller vaccine manufacturers. However, without significant investment (which many of the stakeholders may not have access to), chances of successful products reaching the market remain limited. And with so many global priorities competing for investments, product development is almost certain to take a strong hit. Interestingly, the majority of vaccines in the pipeline are aimed at adapting or improving existing vaccines (e.g., to improve their efficacy or give longer-lasting immunization or to develop combination vaccines), or creating the next generations of existing vaccines. Many of these projects target leading causes of child death including diarrheal disease and pneumonia. This is important, as coverage, adherence, and acceptance is also improved with these types of products. Accelerating access to suitable new vaccines Having a vaccine on the market that meets a health need and is suitable for LMICs does not automatically resolve access issues. Photo: PATH/Aaron Joel Santos To drive strategic R&D decisions that meet public health needs, particularly for low- and middle-income countries, the World Health Organization develops Preferred Product Characteristics (PPC)– recommendations for priority indications, target groups, possible immunization strategies, and desired clinical data, as well as ensuring that vaccine presentation and packaging is suitable for low-resource settings (such as remote populations, or where infrastructure is weak). Together these PPCs and presentation and packaging recommendations form an essential part of vaccine developers’ Target Product Profiles (TPPs). Companies can use these TPPs to assist in defining target product characteristics, such as dosage, target price, target population, and route of administration. Just having a vaccine in the pipeline or even on the market that meets a priority need and is suitable for use in a low- and middle-income country will not automatically solve the world’s access problems. Companies and other stakeholders have a joint responsibility to ensure that there are mechanisms in place to ensure the vaccine’s quick roll-out, thus ramping up coverage of vaccines upon market introduction. Companies are expected to continuously innovate through R&D towards the goals defined in the TPP, and ensure that access provisions are aligned with the needs and intended reach of vital products. Big pharma actions to drive access In our vaccine R&D study, we found that companies have used at least one access provision in 17 percent of the vaccine projects in the pipeline. Out of 70 projects analyzed, 42 are nearing the end of the pipeline, yet only 8 projects have provisions in place for driving access once they hit the market. It is not clear whether access provisions are truly lacking, or whether low transparency accounts for this gap. A close look at the usage of the provisions revealed examples such as tiered pricing strategies aimed at ensuring affordability, the use of local manufacturing capacity based in a developing country to reduce cost and ensure local supply, the use of advanced market commitments, commitments for discounted prices, and commitments to manufacture large volumes at the point of market entry. The systematic application of access provisions will help ensure that successful vaccine candidates are suitable for use in the countries that need them most and align with the needs outlined in the PPCs and TPPs. This could help ensure uptake, acceptance, and coverage is ramped up upon market entry and ultimately more lives are saved. While we indeed need clear incentives for companies to invest in vaccine pipelines, they are encouraged to consider and put in place access provisions as early as phase II clinical stages to develop vaccine candidates with poor, rural, and isolated populations in mind.

Photo: Heng Chivoan When most people think of hunger, they think of a lack of food—a nation suffering from crop failure and famine, or a family that can’t afford to put enough food on the table. But hunger is a far more complex issue with many dimensions. Tackling hunger is not only about ensuring reliable and affordable access to food, but access to the right types of food that are rich with the nutrients human bodies need to function and thrive. Two billion people—more than a quarter of the world’s population—suffer from micronutrient deficiencies, an affliction GHTC member HarvestPlus calls “hidden hunger.” Micronutrient deficiencies, or insufficient amounts of vitamins and minerals, including vitamin A, zinc, and iron, are a major public health problem, particularly in developing countries where people’s diets rely on inexpensive staple crops that often lack nutrients. While those affected may not show the visible symptoms of hunger and malnutrition, micronutrient deficiencies can still have a devastating impact on health, resulting in stunting, blindness, and lowered IQ in children, as well as increased vulnerability to infectious diseases and complications in pregnancy and childbirth. This World Food Day, we’re joined by Peg Willingham, head of Advocacy and Policy at HarvestPlus, to discuss biofortification—an innovative approach to tackling hunger and malnutrition. What role can biofortification play in eradicating hunger, and in particular, micronutrient deficiency? PW: Ideally, everyone should have access to fruits, vegetables, and protein, or to important interventions like vitamin supplements. Unfortunately, these are often out of reach for smallholder farmers who subsist on the food they grow on an acre or two of land—which constitutes the majority of people living in developing countries. A cost-effective new tool to target these families is biofortification—using conventional breeding techniques to increase the levels of vitamins and minerals in the most widely consumed staple foods in Africa, Asia, and Latin America. Can you talk a bit about the process of biofortification and how these crops are introduced and scaled up in developing countries? PW: Until recently, crop developers have focused on higher yield per acre and resistance to diseases, pests, drought, and heat. With support from HarvestPlus, researchers are now including nutrition as an important trait. They search existing seeds banks—which contain 300,000 plant varieties—to identify ones that are naturally high in these important micronutrients, but which cost the same, produce the same yield, and don’t require any extra inputs like more water or fertilizer. National agricultural research authorities around the world then test these crops locally to make sure they grow properly in different soils and climates. We then work with a broad array of partners to get these healthier crops to farmers. This varies from country to country and from crop to crop. For example, most farmers in Zambia buy their corn seed from local private companies, so we work with those firms to get them to make the switch to seeds that are high in vitamin A. In Uganda, farmers who receive donated vitamin A sweet potato vines share them with other farmers the following season, in a constantly expanding cycle. Ten million people are currently growing and eating these healthier foods in more than 30 countries, and testing is underway in almost 20 more countries. What’s in HarvestPlus’ pipeline of biofortified crops? What crops have already been released or are currently in development? PW: Biofortification is centered on the staple foods that people already eat regularly. More than a dozen crops are currently available to farmers: bananas, beans, black-eyed peas, cassava, corn, lentils, pearl millet, plantains, potatoes, pumpkin, rice, sorghum, sweet potato, and wheat. We are excited by recent data demonstrating the nutritional impact of biofortified crops. A study in Mozambique showed vitamin A sweet potatoes significantly reduced the incidence and duration of diarrhea, one of the leading causes of mortality in African children. Pearl millet extra rich in iron was able to reverse iron deficiency in school-aged Indian children in six months. More studies are underway. What role can policymakers—at the national level, as well at the multilateral and global level—play in advancing biofortification and other innovations to improve nutrition? PW: We have been gratified to see how quickly policymakers have embraced this innovation, paving the way for better health and livelihoods. The World Bank has begun funding countries to scale-up biofortification, and the African Union’s commissioner for Rural Development and agriculture and health ministers around the globe have publicly endorsed it. Several countries have included biofortification in their national health and agriculture strategies and are investing their own money in scaling-up access. Additional resources will accelerate this process.