Breakthroughs Blog: HHS

Aedes Aegypti mosquito which carries the Zika virus. Photo: CDC/James GathanyOn Tuesday, the Obama administration announced that it will transfer nearly US$600 million in remaining Ebola funds to fight the growing threat of Zika virus. But many questions remain. Where is the money going? From what accounts will it come? And what does this mean for the Global Health Security Agenda (GHSA) programming which is supposed to help protect against these threats in the future?In February, the President requested $1.9 billion in emergency appropriations to combat the Zika virus outbreak, but authorization was stalled by members of Congress who suggested the Administration reallocate existing funds instead. The Administration continues to stress that the full request is still needed to fight both Zika and complete the Ebola response. With the announcement of the transfer of funds, the Administration is signaling that the risk of waiting for Congress to act on a supplemental funding is too great, and deploying additional funding to address Zika is essential in the short-term—before the summer weather leads to a broader spread of the mosquito-carried virus.Reallocating Ebola funding to address Zika carries consequences. While the Administration acknowledges that some Ebola funds remained unspent, much of this money has been allocated to implement the GHSA—a commitment to help at least 30 countries prevent, detect, and respond to emerging disease threats. GHSA has not received any direct appropriations, largely due to sentiment that remaining Ebola balances should cover the cost. Additionally, as the Ebola response remains unfinished—health systems in West Africa remain fragile and we have not yet developed approved Ebola vaccines or treatments—diverting funding before we have finished the job remains risky.Where is the money going? From where will it come? Vaccine researcher. Photo: NIAID, NIH Because the US Centers for Disease Control and Prevention (CDC) is focused on research and development (R&D) for Zika vaccines, treating those infected, and combating the mosquitoes that spread the virus, many expect the bulk of the $600 million transfer to be directed to CDC Zika efforts. The Washington Post reports that 75 percent of the transfer will go to CDC and the rest to foreign aid accounts. It remains uncertain from what accounts the Ebola transfers will come—and subsequently the impact on programs currently funded through the Ebola supplemental. It seems likely that much of the transfer may come from accounts at the US Agency for International Development and State Department, which as of December 31, 2015, had $400 million in programmed Ebola funds that will expire at the end of fiscal year 2016. Other accounts with remaining funds include: $1.031 billion at CDC for domestic, international, and global health security $363 million at Public Health and Social Services Emergency Fund, which houses the Biomedical Advanced Research and Development Authority $45 million at the US National Institutes of Health $14 million at the US Food and Drug Administration Funds in these accounts do not appear to have expiration dates. As we do not yet know for certain which accounts will fund the $600 million transfer, the impact of this decision on implementation of the GHSA is also uncertain.If funds are transferred from CDC accounts, GHSA efforts could be delayed or stalled. It also remains to be seen whether the Administration will receive additional funding to supplement the Zika response. While Congress has not acted on a request for a stand-alone supplemental funding, members have suggested they are open to providing additional funding in the future should the reallocation of existing funds prove insufficient to both addressing Zika and completing the Ebola response. The possibility remains that we could see additional funding for Zika as part of the regular appropriations process, which is likely to progress in the coming months. 

The US Department of Health and Human Services (HHS) is partnering with New York–based Regeneron Pharmaceuticals, Inc. for the development of an Ebola treatment. The treatment, developed by Regeneron, is comprised of three monoclonal antibodies that help the human immune system identify and bind to the Ebola virus, and thus prevent the virus from entering human cells and reproducing. Through the Biomedical Advanced Research and Development Authority, HHS will contribute up to US$38 million over two years, which will support both the advanced development of the treatment, as well as manufacturing enough doses of the treatment to be used in clinical trials. Swiss pharmaceutical company Novartis announced a new program last week to expand access to 15 of its medicines by offering them to health care providers in low- and middle-income countries for just $1 per drug per month. The program will initially be launched in Kenya, Ethiopia, and Vietnam, but could be expanded to as many as 30 countries. The 15 medicines included in the Novartis Access portfolio treat chronic diseases including cardiovascular and respiratory illnesses, diabetes, and breast cancer. Novartis will partner with governments and nongovernmental organizations to implement the program. Photo credit: CDC/ Melissa Dankel Researchers at Stanford University may have discovered a way to combat Clostridium difficile (C. diff)—a deadly bacteria that affects the intestines—without using antibiotics. C. diff’s virulence relies on a specific toxin—Toxin B—it releases that is responsible for the diarrhea, abdominal pain, and damage to the intestinal wall associated with the bacteria. While broad-spectrum antibiotics combat C. diff and other bacteria by attacking all bacteria—including safe, healthy bacteria—this new approach uses a molecule called ebselen that targets and deactivates Toxin B. The team at Stanford gave mice multiple rounds of antibiotics followed by a multidrug-resistant strand of C. diff; in other words, they made the mice particularly susceptible to infection and then introduced a particularly virulent bacteria. However, the use of ebselen to treat the infection almost completely protected the mice from symptoms. Ebselen is currently being tested for use in humans to treat other conditions, and initial results suggest that it is safe and well-tolerated. The US Food and Drug Administration (FDA) gives breakthrough designation to drugs that treat serious conditions and that have the potential to be significantly better than anything on the market. The FDA expedites the development and review of drugs deemed to be breakthroughs, but the designation is not a guarantee of safety, efficacy, or ultimate approval of the drug. However, a new study suggests that use of the word “breakthrough” could give patients “unwarranted confidence […] which could prevent them from making a fully informed decision about whether to take the drug or not,” according to the study’s coauthor Tamar Krishnamurti. The team recruited 600 online participants, each of whom were given one of five descriptions of a drug that has received breakthrough designation. The first description included just the facts, while the second and third described the drug as “promising” and “breakthrough,” respectively. The fourth and fifth clarified that continued approval of the drug depended on the results of additional clinical trials. In the subsequent survey, participants who read that the drug was “promising” or “breakthrough” were more than twice as likely to describe the drug as very or completely effective. While nearly a third of those who read the “breakthrough” description falsely considered the drug’s efficacy to be proven, compared to only 10 to 16 percent of participants who read the clarification regarding continued approval. All participants were then asked to read two descriptions of the same drug and identify which they would take. Ninety percent of respondents chose the description that used the word “breakthrough.”

The US Food and Drug Administration (FDA) approved the first 3D-printed drug last week, paving the way for the technology to be used to customize medical care to individual patients. 3D printing is a manufacturing process that involves using a computer to create an object one layer at a time. In the case of the recently approved Spritam—a treatment for epilepsy—the printing allowed for greater control over formulation of the drugs, resulting in the creation of the first 1,000 milligram tablets that remain easily dissolvable despite their large size. The use of 3D printers could ultimately enable hospitals to produce their own medicines, adjusting the dose for individual patients. Meanwhile, at the University College London School of Pharmacy, researchers are exploring the possibility of using 3D printing to create uniquely shaped drugs. Drugs are absorbed at different rates depending on the surface area and volume of the tablet, and by adjusting the shape of a tablet (i.e., creating a pyramid or doughnut shaped pill) the rate at which a drug’s active ingredients are released could be manipulated. Leaders at the FDA and the US Department of Health and Human Services propose mechanisms and protocol to expedite drug development in public health emergencies in The New England Journal of Medicine, stating “if we are to act on lessons learned [from the Ebola outbreak] there is no time to waste.” The authors note that limited research capacity delayed the testing of experimental treatments, calling for efforts to strengthen clinical trial infrastructure globally. The outbreak also prompted debate about research ethics in emergency settings (i.e., whether it was ethical to administer untested therapies and the ethics of using placebos in an outbreak). Consequently, the authors recommend that processes for ethical review of studies in outbreaks be streamlined. Finally, the authors stress the need for coordination between health and regulatory authorities, researchers, and product developers. In the Ebola outbreak, the US government partnered with West African governments, academic institutions in both regions, and product developers at every stage. Clinical trials of different therapies were conducted concurrently, allowing partners to have a single, shared control group. The authors note that to facilitate collaboration for rapid drug development in outbreaks, there is a need to establish “model agreements” regarding data management and intellectual property rights. BiondVax Pharmaceuticals announced last week that those vaccinated with an experimental flu vaccine in 2012 had stronger immune responses to strands of influenza that didn’t even exist three years ago. The vaccine was developed to provide broad protection against different strands of influenza, in contrast to the seasonal flu vaccine which protects against the three to four strands of influenza predicted to be the most virulent that year. In 2012, the vaccine (M-001) was tested in phase II clinical trials in which 90 participants—all aged 65 or older—received the vaccine and 30 served as the control group. The vaccine successfully triggered an immune response, including the development of antibodies against several different strains of influenza. Earlier this year, BiondVax exposed blood plasma collected from participants in the 2012 trial to a strain of influenza that did not exist in 2012, and discovered protective antibodies against the strain in 50 percent of the plasma samples from those that received the vaccine, compared to just 10 percent of the samples from those in the control group. As BiondVax’s President Ron Babecoff explains, the vaccine “provides a safety net by broadening the immunogenicity [immune response] to existing and future flu strains.” Next, the vaccine will be tested in phase 3 clinical trials. Blood smear revealing Trypanosoma brucei parasites, which cause African sleeping sickness. (Photo: CDC/ Dr. Mae Melvin) A simple innovation—blue cloth and fine netting sprayed with insecticide between two sticks—could wipe out African sleeping sickness in a mere five to six years. African sleeping sickness is transmitted by tsetse flies, which breed along rivers looking for “something that contrasts with the green vegetation,” according to entomologist Steve Torr, “and for some reason they’re especially attracted to bright blue.” The flies are attracted to the blue cloth and the insecticide kills them within three minutes. The contraption is currently being tested in northern Uganda, where more than 17,000 have been installed over 1,500 square miles; in less than two years, the population of tsetse flies has been reduced by 90 percent. Only 1 in 1,000 flies carry the parasite, and the flies only reproduce once every nine days—whereas mosquitoes lay hundreds of eggs each day—bringing Torr’s team to the estimate of five to six years to both reduce the tsetse population, and eliminate the parasite from the remaining population.

On Thursday, March 26, 2015, the Global Health Technologies Coalition (GHTC) launched its sixth annual policy report titled Meeting the challenge, seizing the opportunity: US leadership can advance global health R&D with a luncheon and panel discussion on Capitol Hill. The recent Ebola crisis was a common theme as panelists discussed what lessons could be learned about the need for further global health research and development (R&D) to enhance America’s preparedness to address future health threats. Dr. Joanne Carter—executive director of GHTC member RESULTS and moderator of the event—opened the discussion by reflecting on recent successes in global health R&D, while also emphasizing the need for increased investments in tools to tackle existing and emerging public health challenges. Carter noted how years of budget stagnation and sequester cuts have stymied the development of promising technologies and eroded US preparedness to tackle global health threats like Ebola. She expressed that “as we have achieved hard fought gains, challenging fiscal circumstances have put funding for global health product development at risk. Global health crises like Ebola and emerging obstacles like antibiotic drug resistance have demonstrated that existing tools are not enough. If we are going to successfully combat these challenges and reach our goal of a healthier world, we must continue to innovate.” Panelist Daniel Bausch, MD, MP&TM—senior consultant for the Clinical Team in the Department of Pandemic and Epidemic Diseases at the World Health Organization—echoed the need for forward-looking investments in R&D and preparedness, noting that the world has spent much more money fighting Ebola than it would cost to prevent the epidemic. Bausch maintained that while the US and global response to the Ebola crisis was unprecedented, we must learn from our failures to combat future epidemics. He underscored that R&D should be treated as a preventative measure, rather than a response to a crisis, reminding the audience that the clinical trial process can take years, even decades. Bausch called for increased long-term US government investments in global health R&D and strengthening health systems and R&D infrastructure in developing nations, noting that in an increasingly interconnected world “US health is global health.” Panelist Ann Mei Chang—executive director of the US Global Development Lab at the US Agency for International Development (USAID)—echoed Bausch’s remarks admitting that the US government is “much better at responding to crises than investing long term.” Bausch further cited the challenges that budget cuts pose for global health researchers, explaining that “if you’re a researcher in a university setting, you probably spend at least 50 percent of your time looking for funding.” He further remarked that research is often stalled because researchers lack the funding to continue their work in an already long and difficult process. Panelist Captain Michael Schmoyer—director of the Office of Pandemics and Emerging Threats at the US Department of Health and Human Services (HHS)—remarked that there were bright spots in the US response to Ebola, including the ability of US agencies to collaborate and work together. He asserted that during the outbreak, coordination between HHS, the Centers for Disease Control and Prevention (CDC), USAID, the Department of Defense (DoD), and the Food and Drug Administration was unprecedented. Captain Schmoyer confessed that agency leaders surprised themselves with their ability to work effectively together and that the response to the Ebola crisis could serve as a model for US agency coordination moving forward. He cited the example of how HHS worked with other agencies including the DOD, CDC, and USAID to set up the first medical unit to care for those healthcare workings responding to Ebola. The other panelists agreed that partnership and collaboration, both across the US government and with other sectors, is essential to advancing global health R&D during times of crises and under normal circumstances. Chang discussed how the US Global Development Lab at USAID advances R&D by leveraging existing funding through diverse partnership from different sectors including the private sectors, nongovernmental organizations, universities, and local government. She emphasized the value of open innovation, through calls for proposals and ideas, to elevate previously untapped voices. Chang cited an example of the value of this collaborative model during the Ebola outbreak. USAID partnered with the White House Office of Science and Technology, CDC, and DoD to launch the Fighting Ebola Grand Challenge for Development, focused on improving the personal protective equipment used by healthcare workers on the front line. Chang said the competition received ideas from engineers, architects, and even wedding dress designers, and now USAID is working with a manufacturer to develop the winning design and introduce it into the field. Captain Schmoyer further endorsed the value of partnership noting that some of the simplest, but most invaluable, ideas generated in the Ebola response resulted from consulting new partners. All three panelists agreed that there were lessons the US could learn from the Ebola crisis to enhance our nation’s preparedness to respond to future health threats. Carter closed the event by noting that “As the world creates a new agenda for global development and seeks to confront existing and emerging health challenges, the time is right for US policymakers to strengthen the nation’s investments in research and product development and reaffirm our resolve to harness American ingenuity to save lives, improve health, and enhance economic prosperity and security around the world.” She called on US policymakers to “meet the challenge and seize the opportunity.” For more information, find the full report here and an accompanying piece on the site Medium.