Kat Kelley

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.

This Monday, May 18 was HIV Vaccine Awareness Day (HVAD), and GHTC members AVAC, the International AIDS Vaccine Initiative (IAVI), and the Bill & Melinda Gates Foundation convened leaders in the field to discuss the state of HIV and AIDS vaccine research and development (R&D). The discussion—which was hosted as both a briefing for congressional staffers and a dialogue among partners—included Dr. Gaudensia Mutua of the Kenya AIDS Vaccine Initiative, Dr. Yegor Voronin of the Global HIV Vaccine Enterprise, and Michelle Dees of IAVI. With worldwide investment in HIV and AIDS vaccine research on the decline since 2007 and some members of Congress calling for further cuts to US investment in this area, the discussion illustrated four key reasons why now is the time to ramp up—rather than scale down—investment in HIV and AIDS vaccine R&D. (1) We are closer than ever to developing an HIV and AIDS vaccine Despite the complexity and mutability of the HIV virus and the difficulty of producing a vaccine, there are currently thirty different HIV and AIDS vaccine candidates in the research pipeline. To ensure that the best candidates advance, strong investments are needed to support this diverse portfolio of vaccines. While most of these candidates are still being tested for safety and for evidence of an immune response, one candidate has already demonstrated partial efficacy. The evidence from that clinical trial has since been used to adjust the vaccine regimen, and the new regimen is currently being tested in another round of clinical trials. (2) We cannot eradicate HIV and AIDS without a vaccine While we have made immense progress in combatting HIV and AIDS with AIDS-related deaths falling by 35 percent since the peak in 2005, eradication will not be possible without a vaccine. For every one person who starts treatment, two more are infected, resulting in 2.1 million new infections and 1.5 million AIDS-related deaths each year. The stigma surrounding the disease continues to impede diagnosis and treatment efforts globally. While existing tools—from antiretroviral treatment to voluntary male circumcision—have had a major impact on reducing the spread of the disease, a vaccine is needed to completely protect against infection. (3) Investments in HIV and AIDS vaccine R&D are producing broader impacts on global health The HIV virus is highly mutable, and is constantly adapting to better fight the immune system. Consequently, many of the standard approaches to vaccine R&D have not proved fruitful. One of the most common types of vaccines—a live attenuated vaccine—involves the use of a weakened, but live version of the pathogen to stimulate the immune system to develop antibodies. The mutability of the virus has made this approach impossible and unsafe. Alternately, scientists often examine the immune response of a survivor to develop a vaccine that will imitate or enhance that process. As no one has ever rid their body of the HIV virus once infected, researchers started the search without a roadmap for what might work. While developing a vaccine that can defend against an ever-changing virus has been a major challenge for scientists, the search has led to invaluable insights into the immune system and progress in vaccinology writ large. Additionally, investments in strengthening HIV and AIDS vaccine R&D capacity in endemic countries have produced broader research and health benefits. For example, the Kenya AIDS Vaccine Institute (KAVI) in Nairobi, Kenya, was established primarily to gather data and conduct clinical trials. However, in addition to the 11 vaccine candidates it has tested in the past 14 years, the institute trained more than 1,500 people between 2010 and 2014. These trainees have been educated in everything from laboratory management and clinical practice to grant writing and vaccine literacy. Additionally, the KAVI facility has been used to test vaccines and drugs for other infectious diseases including Ebola, has helped provide trial participants access to treatment options they may otherwise not have received, and has played a role in combating the stigma of HIV and AIDS in the local community. (4) A vaccine for HIV and AIDS would have enormous financial benefits While the human impact of HIV and AIDS is more than enough reason to invest in vaccine R&D, the continued financial cost of treatment should also be noted. The President’s Emergency Plan for AIDS Relief, which reaches nearly 5 million people each year, spends US$338 per patient per year on HIV and AIDS treatment, and that’s down from an initial $1,100. A vaccine could prevent between 5.2 and 10.7 million new infections and could consequently save $46 to $95 billion over ten years—just in treatment costs. For more information, check out these key messages from AVAC or this video featuring researchers and clinicians across the HIV vaccine field.

How can we get Big Pharma to invest in low-cost antibiotic research and development (R&D)? The Review of Antimicrobial Resistance—a research group led by economist Jim O’Neill and established by United Kingdom Prime Minister David Cameron—proposed innovative answers to this question in its recently released third report, focused on the R&D pipeline for antibiotics. The report calls for the creation of a fund worth US$16 to 37 per decade to provide cash incentives of $2 to 3 billion for pharmaceutical companies that develop new antibiotics and agree to sell them on a not-for-profit basis. Additionally, the report calls for the creation of a Global Antimicrobial Resistance Innovation Fund, worth $2 billion, to support basic research into antibiotics and diagnostics that would enable the strategic use of antibiotics by primary care physicians. O’Neill reiterated that the cost of inaction around antimicrobial resistance could be as high as $100 trillion and 10 million lives by 2050, as detailed in the first report. A group of experts, including Executive Director Bernard Pécoul of the Drugs for Neglected Disease initiative—a member of the GHTC—are calling on governments and other donors to establish a pooled fund to address R&D gaps for antimicrobial resistance, emerging infectious diseases, and neglected diseases. The experts address the aforementioned proposal to incentivize R&D for antibiotics, warning against a fragmented approach, and calling for coordination in not only financing, but throughout the R&D process. Liberia is now considered free from Ebola, after 42 days—twice the maximum incubation period—without a new case, and Guinea and Sierra Leone reported only seven and two cases last week, respectively. As the West African epidemic comes to a close, clinical trials for experimental Ebola vaccines and drugs are underway. The World Health Organization (WHO) hopes that it will be able to test the efficacy of the two drugs, Zmapp and sIRNA, but realizes that it may be challenging to determine the efficacy of the two vaccine candidates, developed by GlaxoSmithKline and a partnership between Merck and NewLink Genetics. Marie-Paule Kieny, assistant director-general for health systems and innovation at the WHO, noted that there are alternative forms of efficacy testing, such as the “Animal Rule,” under which the US Food and Drug Administration will approve a vaccine if it has proven safe for humans and effective in animals with similar immune systems as humans. This rule can be applied for rare diseases or in cases where testing on humans would be unethical. The WHO also hosted an experts meeting on Ebola R&D last week, with the goal of creating a framework for expediting R&D in future outbreaks. While Kieny highlighted recent progress, with drug and vaccine candidates for Ebola moving through the pipeline in months rather than years, an existing framework would allow the WHO to respond rapidly. TB Alliance, a member of GHTC, has initiated clinical trials of “Nix-TB,” the first, all-oral drug regimen for extensively drug-resistant tuberculosis (XDR-TB). TB Alliance is sponsoring the trial in partnership with Janssen Pharmaceutica—who provided a royalty-free license for one of the drugs in the regimen—and three hospitals in South Africa where Nix-TB is being tested. The regimen is comprised of three drugs, including one that is currently undergoing clinical trials independent of Nix-TB and a general antibiotic that has been used off-label to treat TB. There is currently no approved treatment for XDR-TB, and only 16 percent of patients receiving treatment are cured after two years. According to TB Alliance President and CEO Dr. Mel Spigelman, “The launch of Nix-TB is a critical step to achieve the vision of a truly short-course, simple, affordable, and well tolerated universal treatment regimen.”

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.