Breakthroughs Blog: Research Roundup

India is expected to add all of the drugs currently used in the government’s HIV and AIDS and tuberculosis (TB) control programs to its list of essential medicines within the next six months. These drugs are currently available for free in public clinics; many patients, however, prefer private clinics due to perceived discrepancies in quality of care. The list, which was last updated in 2011, sets price caps to ensure that treatments remain affordable—paramount in a nation where more than 70 percent of the population lives on less than US$2 per day. China’s investments in health-related research and development (R&D) are expected to surpass US funding by 2023. The government of China has invested $1.1 billion in drug development since 2011, due to a policy mandate requiring increased funding for life sciences, including the pharmaceutical industry. Meanwhile, US funding for global health R&D has declined or plateaued each year since 2009. China is currently the world’s biggest manufacturer of active pharmaceutical ingredients and is becoming a leading site for contract research organizations, which support preclinical and clinical research for major pharmaceutical companies. The World Health Organization (WHO) issued a guidance document last week regarding a leading medicine for hepatitis C. The new guidance will inform the design of bioequivalence studies, which determine whether a generic is comparable to a patented product. The drug, sofosbuvir, is patented by Gilead Sciences and can cost up to $1,000 per pill. Proof of bioequivalence will be critical for manufacturers aiming to produce a generic drug and ultimately seek WHO prequalification for their product. In her final speech as commissioner of the US Food and Drug Administration (FDA), Dr. Margaret Hamburg defended the agency’s rigorous drug approval process. “Innovation doesn’t matter if the product doesn’t work,” she noted, highlighting the risks of “unsafe and ineffective medical products.” Hamburg’s remarks come as the House of Representatives Energy and Commerce Committee is in the process of developing legislation—known as 21st Century Cures—that calls on the FDA to expedite the regulatory process using its “breakthrough therapy” designation. This designation, which ensures an accelerated review and increased guidance from the FDA, was granted to 31 drugs in 2014. The 21st Century Cures legislation would allow the FDA to review products based only on preliminary clinical trial data and would allow companies to hold off on long-term safety and efficacy trials until after the product was on the market.

The National Institute of Allergy and Infectious Diseases (NIAID) announced last week that two experimental Ebola vaccines appear to be safe for widespread use, based on early results of clinical trials in Liberia. NIAID will now expand its trials to include as many as 1,500 volunteers, testing the vaccine candidates for efficacy. Volunteers will receive either the vaccine candidate developed by GlaxoSmithKline, another developed by NewLink Genetics Corp, or a placebo. Researchers will examine the immune response to the vaccines to see if participants develop antibodies against Ebola. None of the participants will be intentionally exposed to the Ebola virus. Scientists at NIAID have identified several genetic conditions that affect one’s risk for malaria, and which primarily manifest as red blood cell abnormalities. The researchers followed 1,543 children in Mali for three years, during which time they recorded 4,091 cases of malaria. Genetic disorders that either decreased the production of hemoglobin—the protein that transports oxygen in the blood—or led to the creation of hemoglobin C, an abnormal form of the protein, were associated with increased risk for malaria. Two genetic traits—HbAS and homozygous X-linked G6PD deficiency—appear to protect against malaria. The HbAS gene was not only associated with lower risk for malaria, but with less severe cases of malaria in children who contracted it. Researchers at Cornell University have mapped the genome of Ancylostoma ceylanicum, one of two species of hookworm that infect humans. The study identified 31,000 different genes, including those that are active in hookworms during infection. Scientists believe that as many as 70 of those genes could be promising targets for new drugs or vaccines, and plan to start testing experimental vaccines in hamsters this year.

Scientists at Karolinska Institutet in Sweden have identified the protein that explains why people with blood type O are protected from coma and death resulting from severe cases of malaria. Plasmodium falciparum, the parasite responsible for nearly all fatal cases of malaria, releases the RIFIN protein, which causes red blood cells to stick to one another and restrict blood flow, resulting in tissue damage and death. The study, published last week, establishes that the RIFIN protein insufficiently attaches to type O blood cells, despite its strong adherence to type A blood cells. This results in different health outcomes for those with type O blood, as they avoid the severe effects of the parasite. An article in Al Jazeera explored the history of Ebola vaccine research and development (R&D) and the barriers to conducting clinical trials in Sierra Leone today. While Ebola vaccine research began more than ten years ago, multiple promising vaccine candidates have remained in limbo due to a paucity of funding. Last fall, the US government partnered with pharmaceutical companies to expedite the R&D of experimental Ebola vaccines in light of the epidemic in West Africa. The US Centers for Disease Control and Prevention (CDC) and pharmaceutical company Merck & Co. are preparing for clinical trials in Sierra Leone involving 6,000-8,000 health workers. Health workers have expressed concern regarding the safety of the vaccine, and outreach to health workers and potential participants—which the CDC plans to conduct a few weeks prior to the start of the trial—may present a greater challenge than originally anticipated. A new diagnostic device, called the Microlife Vital Signs Alert, could save up to 70,000 mothers each year by alerting health care workers when a woman is at risk of going into shock due to blood loss during childbirth, or if her blood pressure is dangerously high. The device, which only costs US $20, is easy to use and interpret, enabling health care workers—regardless of education and training—to identify when a woman needs to be taken to a hospital with a simple red light.

The US Agency for International Development (USAID) announced last week that Ariel Pabos-Mendez, the assistant administrator for Global Health, will serve as the coordinator for Child and Maternal Survival. USAID stated that his "dual role" will ensure that maternal and child health remains a “central priority” of the Bureau of Global Health. Katie Taylor, who served as the interim coordinator, was named deputy coordinator, and will continue to serve as deputy assistant administrator for Global Health. Researchers at Johns Hopkins University made a groundbreaking discovery about the pathogen that causes tuberculosis, which could ultimately lead to the development of more effective drugs and vaccines. The bacteria generates pieces of DNA that—to the immune cells—resemble and behave like a virus, and thus the immune system responds to the bacteria as though it were a virus. That virus-like piece of DNA, known as c-di-AMP, elicits the production of INF-beta proteins as part of the immune response. The scientists infected mice with tuberculosis bacterium that was manipulated to release elevated numbers of c-di-AMP molecules, and the mice survived twice as long as those infected with normal tuberculosis bacterium. Last week, the US Food and Drug Administration approved LILETTA™, a hormonal intrauterine device developed by Medicines360, a nonprofit biotech company focused on women’s health. Medicines360 is partnering with Actavis to market and lead sales for the device. While the article notes the paucity of nonprofit pharmaceutical companies, it highlights OneWorld Health, which recently merged with PATH and whose founder also founded Medicines360. The organization, which relied on donors throughout the research and development (R&D) of LILETTA™, intends to sustain itself on sales moving forward. The Council on Foreign Relations took an in-depth look at the history of artemisinin, the leading agent used to treat malaria, from discovery through R&D for effective drugs. The search began when the Plasmodium falciparum parasite, which is responsible for the vast majority of malaria cases, developed resistance to existing treatments. In 1967, the Chinese government established a team of nearly 500 scientists, who identified and researched an extensive list of herbs and traditional medicines, ultimately confirming the efficacy of artemisinin in treating malaria. The article is part of a series, the next of which will focus on the market landscape and dynamics for artemisinin-based products.