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The House Energy & Commerce Committee recently passed an amendment—attached to an unrelated bill—that would add requirements for eligibility to the Tropical Disease Priority Review Voucher (PRV) program at the US Food and Drug Administration (FDA). The PRV program, established by Congress in 2007, is intended to incentivize research and development (R&D) for drugs for which there is a critical need but a limited market opportunity. Under the program, the regulatory sponsor of an approved drug for a tropical or rare pediatric disease is awarded a voucher which expedites FDA review of a future product by four months. These vouchers enable companies to enter the market sooner, and several have been sold between companies for up to US$350 million. Of the three vouchers that have been awarded for tropical disease drugs, two were awarded to companies that weren’t actually involved in the drug’s development—they had merely acquired rights to the drug—and in one case, the drug was already approved by other regulatory authorities and available in 80 countries. The amendment, introduced by Congressman G.K. Butterfield (D-NC), would require the regulatory sponsor to demonstrate the need for the product (i.e., the global burden of the disease and demand for the product) and elucidate their plan to ensure access to the product. Vienna-based researchers have developed a vaccine against Toxic Shock Syndrome (TSS), a rare, life-threatening condition resulting from an extreme immune system response to a Staphylococcus infection. TSS is associated with the use of super absorbent tampons, and an estimated half of cases occur in menstruating women. In a phase 1 clinical trial, the vaccine candidate—which contains a detoxified strain of Staphylococcus—proved to be safe and successfully prompted an immune response. The vaccine will next be tested in a larger, phase 2 trial. The team anticipates the vaccine will last for five years and will be used to protect individuals with a compromised immune system who are at greater risk for TSS. Nature took an in-depth look at drug repositioning, in which a medicine developed to treat one disease or condition is used to treat another. Drug repositioning is not a new concept; leading drugs against HIV and AIDS and erectile dysfunction were once intended to treat cancer and angina, respectively. However, the practice is becoming more common. Since 2011, the number of journal articles published on repurposed drugs has increased sixfold to an average of 30 per month and each year three to four new companies focused solely on the practice are established. Generic medicines are a common target, however, there are also many drugs that have passed phase 1 or clinical trials, proving to be safe for use in humans, but that did not have the intended effect. This approach makes drug development cheaper and faster, as phase 1 trials can often be skipped. Repositioning a drug costs $300 million and takes 6.5 years, compared to $2 to 3 billion and 13 to 15 years when starting from scratch. However, phase 1 trials may still be needed if the drug needs to be delivered in a different way or if a different dose is needed. Additionally, many pharmaceutical companies have massive, untapped compound libraries and new technology and software have made it easier to discover ways in which distinct conditions manifest similarly on a molecular level, which allows them to better identify promising compounds to screen for a given condition or disease.

Schistosomiasis, the second most common parasitic disease, infects more than 240 million people each year, and can result in liver failure, bladder cancer, and even death. Schistosomiasis is treated using the antiparasitic drug Praziquantel, however, resistance to the drug has been reported in Kenya and Uganda. Despite its efficacy, the mechanism of action of Praziquantel remains a mystery; scientists don’t understand how it combats schistosomiasis. By comparing the genomes of parasites that are sensitive and resistant to the drug, researchers at the Texas Biomedical Research Institute and the University of Texas have identified genes that are associated with resistance, and have received a US$3.5 million grant from the US National Institutes of Health to further examine the individual genes and mutations that confer resistance. The team will collect parasite eggs from patients in Kenya and Uganda before and after treatment with Praziquantel; the eggs from patients who are cured and those that remain infected will be classified as sensitive and resistant to the drug, respectively. They will then sequence the parasites’ genomes, honing in on the genes and mutations linked to resistance, with the goal of better understanding how resistance develops. This information is critical to developing drugs that are effective against Praziquantel-resistance parasites and diagnostics that can detect resistance. Researchers at the All India Institute of Medical Sciences (AIIMS) have completed successful animal trials of an oral vaccine against hepatitis B using a nanotechnology platform that could be adapted for other viruses. Oral vaccines are challenging to develop, as the key components are often degraded in the stomach before they can be absorbed through the intestines. However, they offer significant advantages: they don’t require needles and consequently there’s no risk of blood contamination, many don’t need to be kept cold, and they often spread more thoroughly throughout the immune system. The existing vaccine against hepatitis B is injectable and requires three to four doses, whereas the vaccine under development at AIIMS could be potent enough to require just a single dose. The team used nanoparticles to house the antigen—the part of the vaccine that triggers an immune response—and covered the nanoparticles in a protective surface that can survive the stomach. The vaccine will next be tested in human clinical trials, which the team hopes to complete by 2021. The World Health Organization (WHO) is proposing new guidelines for yellow fever vaccination in emergencies, as alarming outbreaks in Angola, Uganda, and Peru intensify due to a limited global supply. Clinical trials suggest that the vaccine is effective at much smaller doses, and the WHO is expected to recommend that member states use just one fifth of the standard dose. However, the studies were conducted exclusively in adults, raising concerns that the fractional dose might not be enough to protect children. It’s also unclear if the smaller dose would provide lifelong immunity, and the WHO’s proposal will likely recommend a booster to be administered at a later time. Once complete, the proposal will be submitted to the WHO’s Strategic Advisory Group of Experts on Immunization for review, and if approved, will be implemented if the outbreak reaches emergency levels.

Researchers at the Durham University in the United Kingdom have received a US$100,000 grant from the Bill & Melinda Gates Foundation to test the feasibility of training dogs to detect malaria. Dogs have been trained to use their keen sense of smell to detect other diseases, including certain cancers, and studies suggest that malaria infection causes a distinct odor, and that unique chemicals can be found on the breath of patients. The team plans to recruit 400 children in the Gambia, including many who are currently infected with malaria. The children will wear nylon socks for 24 hours, which will then be used to train the dogs to identify malaria based on odors in the sweat and skin. If successful, this approach to malaria testing would be quick and cheap, and would not require any equipment or a laboratory setting. A new, commercially-available diagnostic can predict premature births, a critical tool as half of all preterm births occur in women without known risk factors. Between 2011 and 2013, the Utah-based Sera Prognostics enrolled more than 5,500 pregnant women at 11 sites across the United States, and confirmed that the quantity of two proteins in the blood can indicate risk for preterm birth. The test can be administered at 19 or 20 weeks into the pregnancy; pregnancy normally lasts 40 weeks and delivery before 37 weeks is considered preterm. The test—PreTRM®—tells a woman her percentage risk, and currently costs $945, however, Sera Prognostics is working with the Bill & Melinda Gates Foundation to develop tools more suitable for low-income countries. Startup NextGen Jane is developing a “smart tampon” that would collect menstrual blood each month and test for a range of diseases and conditions, including sexually transmitted infections, endometriosis, polycystic ovarian syndrome, uterine fibroids, cervical cancer, and more. Many of these conditions are asymptomatic, and consequently go undetected until significant damage has been done. The team at NextGen Jane has a working prototype—a device that siphons menstrual blood from tampons—and is conducting clinical trials for several of the diagnostics themselves, which identify biomarkers for different conditions in menstrual blood. The tool will connect to a database, allowing women to analyze the data and track their reproductive health over time. The team anticipates having a complete product—combined diagnostics and the delivery mechanism—within the next year, which will be commercially available within three to four years.

US Navy Lt. Kimberly Edgel, left, and Christian Baldeviano examine a positive malaria blood smear at Naval Medical Research Unit (NAMRU) 6 in Callao, Peru.This afternoon, the US Senate voted to protect critical medical research programs at the Department of Defense (DoD). In a vote of 66 to 32, the Senate approved Senator Durbin’s (D-IL) Amendment 4369 to the Fiscal Year 2017 National Defense Authorization Act (FY17 NDAA), which strikes sections 898 and 756 in the underlying bill, designed to enact enough restrictions and red tape on DoD medical research to effectively end all existing programs. With this vote, the majority of the Senate signified that medical research is a critical function of the DoD, and must continue to be a priority. Infectious disease and other medical research at DoD plays a vital role in serving the Department’s overarching mission: supporting our military men and women. Not only does DoD infectious disease research directly benefit service members overseas—who experience neglected infectious diseases alongside local communities—but it also plays a key role in domestic health preparedness initiatives that prevent, detect, and respond to infectious diseases that threaten the health of American civilians at home. Beyond threat reduction to Americans, DoD research can often be translated for other contexts, and serves as an important component of US global health efforts to address HIV and AIDS, tuberculosis, malaria, and neglected tropical diseases in low-income countries.For example, malaria, which threatens the lives of nearly 3.2 billion people in tropical and poor regions of the world, is also a significant threat to the operational readiness of the US military. More person-days were lost among US military personnel due to malaria than to bullets during every military campaign fought in malaria-endemic regions during the 20th century. Thanks to ongoing research at DoD, nearly all of the most effective and widely used antimalarials—used to protect our service members overseas and adapted for widespread use in endemic regions—were developed in part by US military researchers. DoD medical research is also critical to medical advances that directly benefit US civilians at home: One of every four vaccines approved by the US Food and Drug Administration in the last century was developed with the participation of DoD. The 2014 Ebola epidemic in West Africa offers yet another example: the Department’s quick work to advance the development of Ebola countermeasures and safety protocols during troop deployment to West Africa was vital to protecting lives of service members and civilians in the region and remains vital to ongoing response efforts.On May 25th, GHTC sent a letter to members of the Senate, urging them to uphold the DoD’s critical medical research programs and oppose provisions in Sections 756 and 898 of the FY17 NDAA, which would limit our nation’s ability to develop medical countermeasures necessary to protect our troops and save lives around the world.GHTC commends Senator Durbin’s leadership on a bipartisan effort to remove these troubling provisions and extend our thanks to the co-sponsors of Amendment 4369: Cochran (R-MS), Reid (D-NV), Blunt (R-MO), Mikulski (R-AK), Murkowski (D-MD), Murray (D-WA), Collins (R-ME), Feinstein (D-CA), Shelby (R-AL), Casey (D-PA), Gillibrand (D-NY), Baldwin (D-WI), Bennet (D-CO), Markey (D-MA), Brown (D-OH), Leahy (D-VT), Hirono (D-HI), Reed (D-RI), Menendez (D-NJ), Tester (D-MT), Coons (D-DE), Kirk (R-IL), Klobuchar (D-MN), Udall (D-NM), Boxer (D-CA), Schatz (D-HI), Moran (R-KS), Sanders (D-VT), Warren (D-MA), Cardin (D-MD), Schumer (D-NY).