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Photo: PATH/Map Photo Agency Gilead Sciences, a California-based biopharmaceutical company, has received US Food and Drug Administration (FDA) approval for Odefsey®, a complete, single-pill regimen for HIV and AIDS. Odefsey® contains tenofovir alafenamide (TAF), a modified version of the antiviral tenofovir, used to treat HIV and AIDS and hepatitis B. TAF is highly effective at entering HIV cells, and thus can be administered in doses a mere ten percent of that required for tenofovir-based medicines. Gilead also recently received a positive opinion from the European Medicines Agency (EMA) on Descovy, another TAF-based treatment. The EMA’s recommendation will be evaluated by the European Commission, which can grant regulatory approval for the 28 European Union member states. Prior to the 2014 Ebola outbreak, the experimental therapy ZMapp had only been tested in non-human primates. The therapy, which is comprised of three antibodies against the virus, is particularly difficult to manufacture, and thus only seven patients received ZMapp during the outbreak. Now, results of the first human clinical trial of ZMapp affirms that the treatment could be an important tool in fighting Ebola. The randomized control trial was conducted by the US National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the governments of Guinea, Liberia, and Sierra Leone. As the spread of Ebola slowed, so too did new cases, and thus the partners could only enroll 72 patients, one-third of the 200 for which they had planned. In the study, all patients received supportive care, including provision of fluids and electrolytes, and half of patients received three doses of ZMapp. Patients receiving ZMapp recovered much faster, in terms of symptoms and presence of the virus in the blood, and the fatality rate was lower for ZMapp recipients: 22 versus 37 percent. Despite the small trial size, NIAID Director Dr. Tony Fauci is optimistic that the FDA will “favorably consider” the results, in light of the dearth of approved Ebola treatments and positive animal study results, in which the drug was 100 percent effective. A team of Google engineers is working with the United Nations Children’s Fund (UNICEF) to develop a platform to track and predict the spread of Zika, a mosquito-borne virus linked to birth defects that was recently declared a Public Health Emergency in Latin America. The platform uses data such as weather and travel patterns to anticipate communities at-risk for Zika, and will be adaptable for use in other outbreaks. Google is also providing a US$1 million grant to UNICEF for mosquito control and behavior change efforts, with the goal of reaching 200 million people throughout the Americas. The company is also working to ensure that helpful, accurate information is readily available to all using the search engine, adding detailed information in 16 languages on Zika prevention and symptoms as well as government public health alerts.

The dapivirine ring (Photo: International Partnership for Microbicides) GHTC member the International Partnership for Microbicides (IPM) announced last week the results of two phase 3 clinical trials demonstrating that a monthly vaginal ring filled with the antiretroviral drug dapivirine can reduce the risk of HIV infection in women. The dapivirine ring is the first long-acting HIV prevention method designed for women, and IPM plans to seek regulatory approval for the product. The trials, conducted by IPM and the Microbicide Trials Network (MTN), enrolled 1,959 and 2,629 HIV-negative women and reduced infection rates by 31 and 27 percent, respectively. Efficacy rates were affected by participant age and adherence: for women over 21—who reportedly used the ring more consistently—the dapivirine ring reduced HIV infections by 37 and 56 percent in the trials led by IPM and MTN, respectively. As IPM Founding Chief Executive Officer Dr. Zeda Rosenberg stated, “These findings give new hope to many women at high risk who need more and different options to effectively protect themselves from HIV.” Researchers at the Scripps Research Institute (TSRI) and the US Army Medical Research Institute of Infectious Diseases have discovered potent antibodies against Ebola that could play a critical role in the research and development (R&D) of Ebola vaccines and treatment. The team identified 300 different antibodies against Ebola in the blood of a survivor, using molecules developed by TSRI to hunt for antibodies. Seventy-seven percent of the antibodies were able to combat the virus in mice, providing protection rates ranging from 60 to 100 percent. The three strongest antibodies all targeted distinct vulnerable spots on a certain protein found on the virus’ surface. Anti-Ebola antibodies have been used before, including in ZMapp™, an experimental treatment deployed during the 2014 Ebola outbreak. However, the number of known, effective antibodies was previously limited. This research also revealed a weak spot on the base of the aforementioned Ebola surface protein. As the virus mutates, so do the surface proteins. However, the base of these proteins remains largely the same, and thus, a weak spot on the base of the protein could be a potential target for manifold strains of the virus. US President Barack Obama is calling on Congress to allocate an additional US$200 million for the President’s Malaria Initiative (PMI), a 30 percent increase that would bring the Initiative’s budget to US$874 million. The funding would enable PMI to expand into three new countries—Sierra Leone, Cote D’Ivoire, and Cameroon; eliminate malaria in Zambia and Cambodia; scale up the use of bed nets; and advance R&D for vaccines, drugs, diagnostics, and vector control methods. As resistance grows to both malaria treatments and insecticides, the need for R&D remains critical. Further, resistance to the leading antimalarial was first reported in Cambodia and the most virulent strains are found on the border between Cambodia and Thailand. Thus, eliminating malaria in Cambodia would impede the global spread of drug resistance. With this new funding, PMI would be able to reach an additional 70 million people, ultimately reaching 92 percent of those in malaria endemic regions.

A vaccine candidate against Rift Valley Fever appears to be safe and effective for livestock and has the potential for use in humans. Rift Valley Fever—which was recently identified by the World Health Organization (WHO) as a leading culprit for the next major pandemic—is often asymptomatic, or manifests with nonspecific symptoms that are easily confused with malaria. However, severe cases can involve vision impairment, brain swelling (encephalitis), hemorrhagic fever, or death. The disease is caused by a virus and transmitted to humans through mosquito bites or contact with infected animal tissue. While there is a veterinary vaccine against Rift Valley Fever used throughout Africa, it does not provide complete protection from the disease and can induce abortion. The vaccine uses a virus that causes cold-like symptoms in chimpanzees, an approach that is generally safe for humans. The candidate will next be tested in animal trials across East Africa, which will be followed by human clinical trials in the region. Middle East Respiratory Syndrome Coronavirus (Photo: National Institute of Allergy and Infectious Diseases (NIAID)) Last week, the Walter Reed Army Institute of Research (WRAIR) initiated the first-ever human clinical trials for a vaccine against the Middle East Respiratory Syndrome (MERS). The DNA-based vaccine was developed by Inovio Pharmaceuticals and GeneOne Life Sciences Inc., and the two companies are also partnering to develop vaccines against Ebola and Zika. MERS is endemic in the Middle East, however, an outbreak last spring in South Korea resulted in 186 cases and 36 deaths. The United States currently has 35,000 and 27,000 troops in the Middle East and South Korea, respectively, and as 40 percent of MERS cases are fatal, “low prevalence doesn’t mean low risk” according to Dr. Kayvon Modjarrad, associate director of the Emerging Infectious Disease Research Program at WRAIR. Meanwhile, a team of researchers at Erasmus Medical Center in Rotterdam is testing a MERS vaccine in camels in Saudi Arabia, where 12 percent of camels are infected at any time and camel-to-human transmission is a significant driver of new cases. Inovio Pharmaceuticals and GeneOne Life Sciences Inc. are also conducting animal studies of their vaccine against Zika, and announced last week that the candidate successfully prompted an immune response in mice, including the development of antibodies against Zika. The partners will next test the candidate in primates and begin Phase 1 human clinical trials by the end of the year. However, vaccine candidates developed by Bharat Biotech in India and the US National Institutes of Health (NIH) are farthest along, according to the WHO. Bharat Biotech will launch animal studies within the next few weeks and the NIH plans to start human clinical trials of at least one of their two vaccine candidates by the end of this summer. As more than 15 groups across government, industry, and academia have joined the hunt for a Zika vaccine, US Congressman Curt Clawson (R-FL) has introduced legislation to further incentivize Zika research and development (R&D), providing companies a 10 percent tax credit for any Zika vaccine R&D costs. The legislation was accompanied by two additional bills, the first of which would reauthorize a program—at US$200 million per year for five years—to support states with mosquito control and prevention. Clawson’s third piece of Zika-related legislation would allow supplemental funding for the Ebola response to be used for Zika, however, leaders at the NIH and US Centers for Disease Control have stated that the remaining Ebola funding has already been reprogrammed and that the agencies have had to take funding away from other programs to kickstart the Zika response.