Breakthroughs Blog: Research Roundup

The zoonotic Middle East Respiratory Syndrome (MERS), which World Health Organization (WHO) Director-General Dr. Margaret Chan called “a threat to the entire world” has spread to South Korea. More than 100 cases and 10 deaths have been reported, making it the largest outbreak outside of the Arabian Peninsula. While there are currently no vaccines or treatments for MERS, researchers are confident that with adequate political will and funding, such products could be rapidly advanced. Photo: PATH/Nguyen Ba Quang Dr. Matthew Frieman, a professor and researcher at the University of Maryland School of Medicine, has developed an experimental vaccine in partnership with vaccine company Novavax Inc. that successfully protected mice against the MERS virus. Greffex, another vaccine company, has already worked with the US National Institute of Allergy and Infectious Diseases to develop a vaccine that triggers the production of antibodies—proteins that protect against the disease—in mice. Dr. Frieman and Greffex CEO John Price agree that funding and political will are the only barriers to the development of a MERS vaccine. According to Price, Greffex could develop a MERS vaccine candidate in less than a month with a sample of the virus, but they lack the funding to conduct clinical trials. Researchers have also struggled to obtain the needed information and materials—including samples of the virus—from scientists in Saudi Arabia. In the meantime, Frieman is working to test existing, approved drugs for the treatment of MERS, and has identified 27 drugs that have demonstrated potential in combatting MERS in a laboratory setting. At this year’s G7 summit, leaders of seven countries—including Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States— pledged to advance research and development (R&D) for neglected tropical diseases and new antibiotics. The members of the G7 committed to supporting everything from basic research through the development of “easily usable and affordable drugs, vaccines and point-of-care [diagnostics].” The G7 Leaders' Declaration also endorses the WHO Global Action Plan on Antimicrobial Resistance and the WHO Global Observatory on Health Research and Development, highlighting the need for improved coordination of global health R&D. In a New York Times op-ed, Gregg Gonsalves and Mark Harrington, co-founders of the Treatment Action Group, reflected on lessons learned about the US Food and Drug Administration’s (FDA) drug approval process during the US HIV and AIDS epidemic. The article comes as Congress is considering the 21st Century Cures Act, a bill intended to advance medical breakthroughs, in part through FDA reform. The legislation includes several provisions to expedite the approval of drugs and medical devices based on what Gonsalves and Harrington consider to be “lower standards.” The authors assert that while innovative regulatory pathways—such as the Accelerated Approval Program—enabled early access to new HIV and AIDS drugs, pharmaceutical companies were still required to demonstrate the safety and efficacy of products before they entered the market. Additionally, in the case of preliminary approval, companies were expected to continue and complete clinical trials. To protect patient safety, Gonsalves and Harrington argue that such standards should be upheld, reminding Congress that those standards “paved the way for the development and approval of breakthrough drugs [that] have been proven to be effective and safe.” There are nearly 170 contraceptives products in the R&D pipeline, from discovery, through product development, to regulatory review. Researchers, advocates, funders, and procurement agencies can now find information about these products all in one place through Calliope, the Contraceptive Pipeline Database, a new resource developed by GHTC member FHI 360. Calliope includes information regarding the R&D stage, the partners, the active pharmaceutical ingredients, the delivery and duration, and the mechanism by which the technologies prevent pregnancy. The contraceptive pipeline is diverse, and includes vaccines, microbicides, implants intrauterine devices and balls, pills, and even microchips. The exchange was created to galvanize contraceptive R&D for low-resource settings through knowledge sharing and the facilitation of cross-sector partnerships.

Leishmania sp. protozoan (Photo: CDC/ Dr. George Healy) The Drugs for Neglected Diseases initiative (DNDi)—a member of the GHTC—is partnering with pharmaceutical companies Eisai Co., Shionogi & Co., Takeda Pharmaceutical, and AstraZeneca to accelerate early-stage research for drugs against Chagas and leishmaniasis. The project, known as the Drug Discovery Booster, will enable DNDi to search through all the pharmaceutical companies’ vast libraries of chemical compounds simultaneously. DNDi will provide each company with a ‘seed’ compound which has shown some ability to combat the parasites responsible for the diseases, and the companies will subsequently scan their libraries for similar, and potentially more promising, compounds. DNDi will then test the compounds identified by the pharmaceutical companies and pick a new seed compound from the results. This process will be repeated up to three times. The GHIT Fund—a member of the GHTC that subsidizes research and development for neglected tropical diseases—is supporting the involvement of the three Japanese pharmaceutical companies. The World Health Organization updated its medical eligibility criteria for contraceptive use last week, adding long-acting, hormonal contraceptives to the list of recommended contraceptives. The list is widely used by medical practitioners to identify the best contraceptive methods for their patients and by policy-makers in shaping national strategies that determine the availability of different methods within their countries. Under previous guidelines, health professionals were advised not to prescribe hormonal contraceptives to women within the first six weeks after giving birth. Revising that recommendation is expected to increase contraceptive access for new mothers, enabling healthy birth spacing and ultimately reducing maternal and child mortality. This is particularly important in light of the results of a recent study in Contraception across 21 low- and middle-income countries, which indicates that more than half of pregnancies in women who have previously given birth occur too soon after delivery to be safe. An experimental diagnostic known as VirScan can identify virtually every virus a person has ever been exposed to using just a drop of blood. VirScan detects antibodies—proteins that the immune system makes to combat infection—and has been tested on 569 people across the United States, South Africa, Thailand, and Peru. The test costs US$25 and currently takes two days to two months to complete. However, the researchers believe that if a company were to lead and streamline its use, the process could reliably be cut to two to three days. Initial results indicate that the average person has been exposed to 10 virus species, however, those in the United States have generally been exposed to fewer viruses, which could be attributable to “differences in population density, cultural practices, sanitation or genetic susceptibility.” VirScan could be used to identify viral causes or catalysts of chronic or autoimmune diseases, as well as global disease patterns.

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.