Breakthroughs Blog: Research Roundup

The French pharmaceutical company Sanofi purchased a priority review voucher (PRV)—which entitles the owner to an expedited review of a future product by the US Food and Drug Administration (FDA)—for US$245 million last week. This particular sale was part of the Rare Pediatric Disease PRV, which was modeled after the Neglected Tropical Disease PRV—a program intended to incentivize research and development (R&D) for neglected diseases, as the market for drugs to treat these conditions is often limited. The voucher significantly expedites the FDA’s review process, from 10–12 months to 6–8 months. This voucher was awarded to Retrophin for approval of a drug to treat bile acid synthesis disorders, which are considered rare pediatric diseases. Only two vouchers have been awarded through a PRV program, the first of which was sold to Sanofi for $67 million and the second to Gilead Sciences for $125 million. Delegates from the World Health Organization’s (WHO) 194 member states approved a resolution at the World Health Assembly—the organization’s annual convening—to address the spread of antimicrobial resistance. The resolution establishes a global strategy to control and prevent the spread of drug-resistant infections, including through the R&D of new antibiotics. Under this new resolution, member states will be required to develop and implement national plans to combat antimicrobial resistance within the next two years. WHO Director-General Dr. Margaret Chan assured delegates at the World Health Assembly that the WHO will provide technical support to national governments as needed, stating “we are going to do our utmost to support you.” The status and progress of these efforts will be reported to the World Health Assembly in May 2017. Photo: World Health Organization The global action plan, presented by the WHO Secretariat during the World Health Assembly, called for improved surveillance; increased awareness; and adequate, sustainable R&D funding surrounding the growing threat of antimicrobial resistance. The plan notes the “serious market failure” for antimicrobial R&D, calling for new mechanisms to incentivize and accelerate the development of new antibiotics. Senators Patrick Leahy (D-VT) and Chuck Grassley (R-IA) recently introduced the bipartisan Patents for Humanity Program Improvement Act, which expands the Patents for Humanity program at the US Patent and Trademark Office (USTPO) to ensure small businesses can participate. Each year, USTPO identifies approximately ten products that have been patented through their office and that have since been used for humanitarian purposes, and provides the winners with a voucher for an expedited patent application, ex parte reexam, or ex parte appeal. The legislation would make the voucher transferable, which would encourage small businesses or individual researchers or inventors—who may not anticipate future patent applications or dealings with USTPO—to participate.

Members of the European Parliament are calling on the European Commission to adopt a resolution to combat the growing threat of antimicrobial resistance—which kills 25,000 Europeans annually. The proposal calls for both “pharmaceutical innovation” and “new revenue models whereby economic returns for companies [are] de-linked from prescribed volumes of antibiotics,” noting the role of public-private partnerships in research for new antibiotics. The proposal also includes measures to promote responsible human and veterinary use of antibiotics, including public awareness campaigns and physician training; monitoring and regulation of antibiotic prescription and sales; and improved diagnostic procedures to ensure appropriate use of antibiotics. Across the Atlantic, the United States Food and Drug Administration (FDA) wants to address the paucity of data on antibiotic use in farm animals to better assess the impact of this practice on growing antimicrobial resistance. The FDA is collecting public comment on a proposal which would require drug companies to report sales for antibiotics approved for livestock, disaggregated by use in cattle, pigs, chickens, and turkeys. While sales of these antibiotics increased by 20 percent between 2009 and 2013, several major poultry producers—including Tyson Foods and Perdue—have promised consumers significant cuts in antibiotic use. Meanwhile, Congresswoman Louise Slaughter (D-NY) is reintroducing the Delivering Antimicrobial Transparency in Animals Act which would require major farms to report on agricultural antibiotic use. The House Energy & Commerce Committee unanimously approved the 21st Century Cures Act on Thursday, a bill intended to support research for and expedite the approval of medical breakthroughs. The legislation is the result of a year-long effort, led by the committee Chairman Representative Frank Upton (R-MI) and member Representative Diana DeGette (D-CO), which involved a series of hearings, testimonies, white papers, and requests for public comment to identify the best policy approaches to advance medical cures. The committee has already developed a US$13 billion deal to pay for the legislation’s provisions, including $10 billion for research conducted by the United States National Institutes of Health and $550 million for regulatory efforts at the FDA. As these funds would be mandated, rather than subject to the appropriations process, they are exempt from sequestration budget caps. The bill’s cost will be offset by the sale of oil from the Strategic Petroleum Reserve and changes to government Medicare payments, including delayed payments to insurance companies.

United States Representatives Jim Cooper (D-TN) and Cynthia Loomis (R-WO) introduced the Research for All Act last week which calls for the inclusion of more women in clinical trials for products submitted for US Food and Drug Administration (FDA) approval. Drugs can have different effects on women and men, and as women are often underrepresented in clinical trials, there have been products on the market that are unsafe or less effective for women. While the FDA has made strides in recognizing and addressing this disparity and its potential consequences, this bill would require the FDA to “ensure that the design and size of clinical trials for products granted expedited approval … are sufficient to determine the safety and effectiveness of such products for men and women using subgroup analysis." Opponents fear that this legislation could increase the cost or length of clinical trials and consequently, product development. Mark Prausnitz, director of the Center for Drug Design, Development, and Delivery at the Georgia Institute of Technology, has created a small patch covered with 100 minute needles intended to administer vaccines without a syringe and needle. Not only would the vaccination be virtually painless, but it could be self-administered, and it would not need to be refrigerated, making it accessible in remote areas with a paucity of skilled health workers or unreliable electricity. The patch has been used successfully to administer the measles vaccine to animals, and clinical trials in humans are expected to start in 2017. Prausnitz will also be testing a flu vaccine patch on 100 volunteers this summer. While the vaccine’s cost will remain the same, Prausnitz hopes the patch will be cheaper than syringes and needles. Researchers at the University of Notre Dame have created simple, paper cards that can identify low-quality or counterfeit malaria medicines. The cards have 12 bars that change color when exposed to a crushed-up pill, and those bars indicate the presence and quantity of six different antimalarial agents. One third of antimalarials in sub-Saharan Africa are either entirely fake, diluted with different ingredients, or contain inadequate amounts of the antimalarial agents. These drugs can cause drug resistance and the additional ingredients can be harmful to patients. The cards, which currently cost US$0.50 each, are intended for use by pharmacists and customs offices, but only work for non-artemisinin-based antimalarials. The leading approach to treating river blindness—mass administration of the medicine ivermectin—can be deadly to patients co-infected with Loa loa worms. However, the detection of these worms can be a challenge, requiring a microscope and a health worker trained to identify the worms in the patient’s blood. Daniel Fletcher, a professor of bioengineering at the University of California, Berkeley, has developed a microscope that connects to a smartphone, takes a video of a blood sample, and detects the movement of Loa loa worms. The entire process takes about three minutes, a much shorter process than transporting a blood sample to a laboratory and counting the worms individually. While this device is an invaluable diagnostic tool, the article highlights the need for research and development of a drug that can combat both the Loa loa worms and the parasites responsible for river blindness.

United States President Barack Obama announced last week his intent to nominate Gayle Smith, senior director for Development and Democracy at the National Security Council, to lead the US Agency for International Development (USAID). Since joining the National Security Council in 2009, Smith has led the Obama administration’s global health work, including the Global Health Initiative and the Global Health Security Agenda. Ambassador Alfonso Lenhardt, deputy director of USAID has served as the acting director since Rajiv Shah stepped down from the post in February. The Universities Allied for Essential Medicines (UAEM)—a global network of students from more than 100 universities in 20 countries—released its second annual University Report Card: Global Equity & Biomedical Research, which evaluates leading US universities on their commitment to neglected disease research. The universities are ranked on innovation, which is measured by investments in neglected disease research; access, or efforts to license new products to ensure affordability and use; and empowerment, which relates to global health education at the university. Johns Hopkins University tops the list, receiving an A- overall, and is followed by Emory University, University of Washington, Harvard University, and University of California San Francisco. The Bill & Melinda Gates Foundation recently brought together nearly 100 representatives from foundations and governments to discuss the impact of Grand Challenges—calls for open innovation in which funding is offered to the best idea(s). The meeting focused on the difficulty of measuring the impact of Grand Challenges, and participants identified key barriers to evaluating and marketing the process. As failure is an inevitable but worthwhile part of innovation, participants have faced difficulties in “selling” Grand Challenges (i.e., to policymakers or donors). Additionally, the complexity and length of the pathway from research and development to utilization of a product makes it hard to pinpoint the exact impact of a Grand Challenge, and while short-term milestones can be assessed, it can take years or even decades before basic research is translated into a lifesaving product.