Faces of Innovation: Hannah Wu, researcher at Brown University

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign-up now to receive our weekly R&D News Roundup email.  Indian generic drug manufacturer Cipla and the Drugs for Neglected Diseases initiative have developed a new, palatable pediatric formulation of HIV medicines priced at US$1 day, which experts say could save the lives of thousands of children each year. The drug, called Quadrimune, contains four HIV drugs—ritonavir, lopinavir, abacavir and lamivudine—and comes in strawberry-flavored granules the size of grains of sugar that can be mixed with milk or sprinkled on baby cereal. The granules are also coated with a polymer that doesn’t melt until it hits the stomach, eliminating the need for cold transport or storage of the drug, which can be inconsistently available in rural areas, especially in sub-Saharan Africa. Quadrimune is still under review by the US Food and Drug Administration and, if approved, will likely lead to rapid certification by the World Health Organization. Each year, approximately 80,000 babies and toddlers die of AIDS in part because their medicines come in hard pills or bitter syrups that are very difficult for small children to swallow or keep down.Final data from a landmark clinical trial of four Ebola therapies in the current outbreak in the Democratic Republic of the Congo show two of the drugs dramatically reduce the risk of dying from the disease, especially in those who started treatment quickly after the onset of their illness. Findings of the PALM trial show that a monoclonal antibody cocktail called REGN-EB3, made by Regeneron Pharmaceuticals, and a single monoclonal antibody developed by the US National Institute of Allergy and Infectious Diseases called mAb114 led to a survival rate of about 65 percent in treated patients compared to 33 percent in the overall outbreak. The other two products tested in the trial, an antibody product called ZMapp and the antiviral drug remdesivir made by Gilead Sciences, did not perform as well, saving only half the patients who were treated with one of those two therapies. The PALM trial began November of last year but ended early in August of this year because an interim analysis showed REGN-EB3 and mAb114 were statistically better than ZMapp and remdesivir.When babies are born with HIV, starting treatment within hours to days is better than waiting a few weeks or months, which is the norm in many countries. The findings from a small study in Botswana, funded by the US National Institutes of Health, show that very early treatment limits how HIV takes root in a newborn’s body, shrinking the “reservoir” of the virus that hides out waiting to rebound in case the children stop taking their medication. The study also demonstrated that the earliest-treated children had more normal functioning of some key parts of their immune system. These findings could influence care in regions hard hit by the epidemic and offer clues as scientists pursue a cure. Though it has become routine practice to give pregnant women a cocktail of anti-HIV drugs to prevent mother-to-child transmission of the virus, it is estimated that 300 to 500 infants are infected every day in sub-Saharan Africa.

The World Health Organization (WHO) recently announced that at its upcoming Executive Board meeting in February, member states will discuss challenges and issues in implementing the Nagoya Protocol—a legal framework that governs the access to and benefits gained through the sharing of genetic resources, including human and animal DNA, plants, and pathogens. As these discussions heat up, GHTC is taking a brief look at what the Nagoya Protocol is, how it impacts global health research and development (R&D), and what’s next for the future of this framework.WHAT IS THE NAGOYA PROTOCOL?The Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization‒or Nagoya Protocol for short‒is a legal framework that went into effect in 2014. It regulates the sharing of genetic resources, including human and animal DNA, cultures and specimens, plants, and pathogens that are used in the course of R&D.Origin and goalThis protocol supplements a United Nations treaty, endorsed over a decade earlier in 1992, called the Convention on Biological Diversity (CBD), which established a basic principle: That every country has sovereignty over the genetic resources found within its borders. Its broader goals were to support the conversation of biological diversity, ensure its sustainable use, and ensure the “fair and equitable sharing” of the benefits derived from the use of genetic resources.The Nagoya Protocol was established to advance that third and final goal by creating greater legal certainty and transparency for both the providers and users of genetic resources. The protocol establishes more predictable paths for gaining access to genetic resources and creates frameworks for tangible agreements that outline the benefits that a donor country will receive in exchange for providing access. It also requires that users comply with any national legislation or regulatory requirements in the provider country governing the collection, use, or storage of these resources.  How does it work in practice?When a researcher, company, or institution wants to access the genetic resources in a foreign country that is party to the protocol, it should start by obtaining a prior informed consent from the country where the materials are located and outline the goal of the planned research and use. Second, the party seeking access and the provider country should also negotiate and reach “mutually agreed terms” that set conditions for the use of the genetic material and define the benefits arising from their use, such as when commercial products results from such research. These benefits could be monetary, such as a lump-sum payment or a share of the profit, or non-monetary, such as transfer of knowledge, technology, or training. A healthy debate over the Nagoya ProtocolThe aim of the protocol is to stop piracy of genetic materials across borders. Sovereignty is at the heart of the matter. Health authorities in low- and middle-income countries are often concerned that providing genetic resources will not yield a tangible benefit to their country or that the genetic materials will be shared without their consent and result in health innovations that may ultimately be unaffordable to their population. Ensuring that there are access provisions in place is critical.On the other hand, the provisions of the Nagoya Protocol can have a negative impact on international research collaborations. From basic research through clinical trials, medical research is highly collaborative and routinely involves the sharing of organisms, cultures, and research findings across borders. Adhering to the protocol can place a heavy bureaucratic burden on researchers and their institutions or companies who must comply with its requirements, as well as the procedures or laws of individual countries, which can vary greatly. The process of obtaining prior-informed consent and reaching mutually agreed terms between users and countries can take several weeks or months, putting research temporarily on hold.CONSEQUENCES AND POTENTIAL IMPLICATIONS ON HEALTH R&DThese delays can have serious consequences to public health. For example, in late 2018, implementation of the Nagoya Protocol in several countries caused significant delays in sharing seasonal influenza strains. Given selecting the strains for each year’s seasonal flu vaccine is a time sensitive process and researchers need genetic material to make this determination, this resulted in a delayed seasonal vaccine rollout and lack of public health preparedness to address influenza.Many fear that the protocol could cause similar challenges in detecting and responding to emerging infectious diseases, including advancing medical products, given pathogens spread regardless of national borders and creating control measures requires partnerships and sample and data sharing between countries and research institutions. Long negotiations to obtain specimens for research potentially increase the risk of disease spreading in populations that have no immunity and can harm the global interest of protecting against emerging infectious diseases.WHAT’S NEXT FOR NAGOYA?Given the potential impacts that the Nagoya Protocol could have on the development of vaccines and other medical products, many stakeholders are calling for exemptions to the protocol and for alternative approaches for the sharing of genetic materials to be considered. In the aftermath of the of the swine and avian flu a decade ago, WHO developed an agreement called the Pandemic Influenza Preparedness Framework, which outlines a potential path forward to mitigate unforeseen health consequences related to the protocol. The agreement provides for global sharing of pandemic influenza viruses within a network of public health laboratories. Organizations and companies outside of this network can also access this pool of viruses after making a partnership contribution to and signing a material transfer agreement with WHO, in which they agree to share benefits. While the agreement only covers flu, some see it as a model that could resolve the disputes over the Protocol and genetic materials and sequence sharing, and create a timelier pathway for researchers looking to combat emerging infectious and other global diseases.