Breakthroughs Blog: Congress

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.

As 2015 draws to a close, the Global Health Technologies Coalition is reflecting on the past year in global health innovation. Below, in no particular order, are our picks for the top global health research and development (R&D) news and stories that shaped 2015. First ever vaccine against dengue virus approved The world’s first vaccine against dengue fever was approved by the national regulatory authority of Mexico, marking an important initial step in preventing this mosquito-borne infection, which is spreading worldwide. Nearly half the world’s population now lives in dengue-endemic countries, and an estimated 390 million infections occur each year. The vaccine’s developer Sanofi spent over 20 years and US$1.65 billion developing the vaccine and is now pursuing regulatory approval in 19 other countries. Sanofi has stated it will make the vaccine available for sale at a “fair, affordable, equitable, and sustainable price.” NIH finally receives funding boost Christmas came early for the US National Institutes of Health (NIH). After years of stagnated funding, NIH—the world’s leading public funder of neglected disease R&D—will finally receive a funding boost in 2016. In the fiscal year 2016 omnibus spending package, Congress approved a $2 billion—nearly 7 percent—increase in funding for NIH from $30 billion to $32 billion. NIH has lost 22 percent of its purchasing power since 2003 due to inflation, so this boost will provide critically-needed funding for the agency to continue to build upon its record of leadership in global health R&D. Photo: PATH/Satvir Malhotra Availability of the first child-friendly, appropriately-dosed TB medicines announced Health workers will soon have a critically-needed new tool to improve treatment for the one million children infected with tuberculosis (TB) each year. In November, TB Alliance and partners announced that the first-ever appropriate, child-friendly tuberculosis (TB) medicine in the correct dose will be available in early 2016. At the moment, TB medicines are not available in appropriate doses for children, so parents must crush or cut the pills to administer. This arduous process—combined with the bitter taste—leads to poor adherence. The new treatments are strawberry- and raspberry-flavored, appropriately-dosed versions of the three most commonly used TB medicines. These new treatments are expected to significantly improve TB treatment and adherence among children. Global Health Innovation Act passes House An important new piece of global health legislation championed by GHTC—the Global Health Innovation Act—passed the US House of Representatives earlier this month. This legislation would strengthen global health R&D programming at the US Agency for International Development (USAID) by directing USAID to incorporate R&D across its global health programming and requiring the agency to report annually to Congress on its R&D programs and activities. In 2016 the hard work will begin again to get the Senate to introduce and pass companion legislation so the bill can move another step closer to becoming US law. Ebola product development advanced at lightning speed After years of slow and stunted progress in the development of drugs, vaccines, and diagnostic tools to fight Ebola, product development jumped forward by leaps and bounds in 2015. Thanks to the collaboration of developers, regulatory agencies, and the World Health Organization, six Ebola diagnostics were developed and deployed in West Africa under emergency measures, early-stage clinical trials are underway for at least two Ebola drug candidates with others in development, and at least 15 vaccine candidates are in development with two candidates undergoing Phase II/III trials. The most advanced vaccine candidate VSV-EBOV was shown to offer near-total protection, according to preliminary data analysis from the trials. While these products arrived too late to have a major impact during the epidemic, the accelerated development approaches and mechanisms used may be able to be emulated to speed product development in the future. New pediatric malaria treatment receives positive scientific opinion paving path for regulatory approval A new pediatric malaria medicine— Pyramax® Granules—will soon be available for children worldwide. In November, Pyramax® Granules received a positive scientific opinion from the European Medicines Agency (EMA) under Article 58, a mechanism which facilitates regulatory approval of the product in malaria-endemic countries. The medicine, which was developed by Medicines for Malaria Venture (MMV) in partnership with Shin Poong Pharmaceutical Co. Ltd, is a combination of two antimalarials and is designed to be easy for children to consume. It is taken in liquid form and is flavored to mask the bitter taste. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. Several promising global health products advancing through development The pipeline of global health technologies is growing and maturing with several exciting products moving through critical development stages. For example, a new medicine for drug-resistant TB became the first new TB drug to advance into clinical trials in six years when it entered Phase I trials in February, a vaginal microbicide containing a novel antiretroviral drug to prevent HIV entered Phase I trials in November, a drug candidate with the potential to become the first ever, oral-only, single-dose treatment for sleeping sickness completed Phase I trials in September, and a microbicide vaginal ring is completing Phase II trials with results expected in early 2016. Due to increased attention and investment over the last 15 years, there are now nearly 500 neglected disease product candidates in the pipeline. Global goals recognize importance of health R&D In September, global leaders ratified a new set of global goals, called the Sustainable Development Goals (SDGs), which will guide global development efforts for the next 15 years. GHTC was excited to see these goals recognize the importance of global health R&D with inclusion of a target supporting R&D of vaccines and medicines for diseases primarily affecting developing nations. It’s been broadly recognized that we cannot reach the ambitious SDG health targets—to reduce maternal and child mortality and end the epidemics of HIV/AIDS, TB, and neglected tropical diseases— by 2030 with the health technologies we have today. Now that the goals and targets are in place, accountability is key. We must ensure the SDGs translate into greater investment and political commitment from all nations to catalyze development of the next generation of health technologies needed to transform global health.

Pyramax® Granules (Photo: MMV) After four successful Phase 3 clinical trials enrolling more than 3,500 patients in 18 countries, the European Medicines Agency (EMA) has granted Pyramax® Granules, a pediatric malaria medicine, a positive opinion under Article 58—a mechanism through which the EMA reviews and issues a scientific opinion on products that are not intended for use in Europe. Pyramax® Granules is a combination of two antimalarials and was developed by Medicines for Malaria Venture (MMV), a member of the GHTC, in partnership with Shin Poong Pharmaceutical Co. Ltd. The treatment is designed to be easy for children to consume: its bitter taste is masked and it is taken in liquid form, as children often struggle to swallow pills. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. A recent article in NPR: Goats & Soda examines Zika virus, a disease transmitted by the same mosquito vector of dengue fever and chikungunya, that has been rapidly spreading throughout South America and the Pacific Islands in recent years. One in five individuals infected with the virus experience Zika fever, which in addition to fever involves rashes, joint pain, conjunctivitis, headaches, vomiting, and muscle pain. Cases of Zika fever are likely underdiagnosed, as awareness of the disease is limited and its symptoms are similar to infections associated with other members of the Flaviviridae virus family, including dengue fever, yellow fever, West Nile, and Japanese encephalitis. There are no reported deaths to date, but there is growing evidence that the virus can be transmitted sexually or from mother to infant during pregnancy. As there are no vaccines or drugs for Zika fever, treatment involves addressing the symptoms, using fever reducers and painkillers. A group of global health advocacy organizations—including GHTC members the Drugs for Neglected Diseases initiative, TB Alliance, Infectious Diseases Society of America Center for Global Health Policy, Sabin Vaccine Institute, and Treatment Action Group—sent an open letter to the US Senate Health, Education, Labor and Pensions (HELP) committee, calling for amendments to the priority review voucher (PRV) program at the US Food and Drug Administration (FDA) to ensure it adequately incentivizes research and development (R&D) for neglected diseases, as intended. Under the program, companies that receive FDA approval for a drug for a neglected disease (see list of eligible diseases) are awarded a voucher for expedited FDA review (six months rather than ten) of a future product. The vouchers are transferable and have been sold at increasing rates, the most recent going for US$350 million. The letter calls for PRVs to only be awarded for products that are "truly new" as two of the six vouchers that have been awarded were for products that had long been in use outside of the United States.[1] The organizations are also calling for recipients of the voucher to be required to develop a strategy to ensure the product is made affordable and accessible to patients in the countries in which the eligible disease is endemic. The United Kingdom (UK) announced last week the creation of the Ross Fund which will provide £1 billion ($1.5 billion) over five years to fight malaria and other infectious diseases. The funding, which will come from the UK overseas aid budget, includes £90 million for malaria eradication; £100 million for infectious disease R&D; £115 million for the development of drugs, diagnostic, and insecticides for malaria, tuberculosis, and other infectious disease resistance; and £188 million for biodefense and rapid response systems for epidemic preparedness. Global Good has developed a cooler that can store and transport vaccines at freezing temperatures for over a month using just ice and no electricity. The Arktek cooler uses vacuum thermal insulation, an approach used to preserve spacecraft entering extreme temperatures. The cooler has been tested in Senegal (with support from GHTC member PATH) and Ethiopia, and last year, the Arktek was modified for use in Ebola vaccine clinical trials, during which the cooler kept the vaccines between -76 and -112 degrees Fahrenheit for three days. [1] There are two separate PRV programs at the FDA, one for neglected tropical diseases and one for rare pediatric diseases. Of the six PRVs that have been awarded, three each have been for neglected tropical diseases and rare pediatric diseases. Since the beginning of the PRV program, six PRVs have been awarded—three for neglected tropical diseases and three for rare pediatric diseases.  

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Now that members of Congress are back in their Capitol Hill offices after five weeks of recess, lawmakers must decide what to prioritize and what to push off in the few short weeks left in session before members hit the campaign trail for the upcoming November mid-term elections. In the latest post on Breakthroughs, GHTC Senior Policy and Advocacy Associate, Jenny Howell, provides a breakdown of what lawmakers should do to ensure global health research and development gets the support it needs. Federal funding in the United States for biomedical research has declined by more than 20 percent in the last decade. At the same time, more scientists are competing for a smaller pot of money. NPR highlights two stories of researchers forced out of science because they either can’t get research funding or “because the rat race has simply become too unpleasant.” Scientists at the National Institutes of Health (NIH) have discovered an HIV antibody that could be effective in fighting the deadly disease. According to the scientists, the antibody—called 35O22—can prevent 62 percent of known HIV strains from infecting cells. The NIH-led scientists also found that the antibody closely resembles antibodies that naturally occur in HIV, which could help in the development of an eventual vaccine. Results from a recent clinical trial could change the approach researchers take on the delivery and development of tuberculosis (TB) drugs in the future. While the REMoxTB trial did not successfully prove TB treatment times could be shortened from six to four months by substituting antibiotic moxiflacin for a currently used drug, it did prove that moxiflacin was safe to use to treat TB on its own. Also, because the trial was one of the largest ever for a new TB regimen, the trial left a stronger research infrastructure to conduct other trials in the future. The Bill & Melinda Gates Foundation has committed $50 million to fight Ebola in West Africa. According to Gates Foundation CEO Susan Desmond-Hellmann, the new money will be available for emergency operations and to help develop drugs, diagnostics, and vaccines to fight the disease. The Gates Foundation’s commitment is the largest sum to ever for one outbreak.