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In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. In a United Nations Foundation blog post, Carla Koppell—chief strategy officer at the US Agency for International Development—notes that much remains to be done to achieve the Millennium Development Goals (MDGs) and argues that accelerating progress on the MDGs in the last 500 days will require harnessing the power of science, technology, and innovation. GHTC member Aeras has announced the initiation of a large, multi-country Phase IIb clinical trialto test a novel vaccine candidate’s ability to prevent tuberculosis in adults. Aeras and GlaxoSmithKline Vaccines, S.A. will evaluate the efficacy, safety, and immunogenicity of GSK’s vaccine candidate, M72/AS01E, and will enroll more than 3,500 healthy adults ages 18-50 years old in sub-Saharan African. The Kaiser Family Foundation has developed an interactive US global health budget tracker that will include regularly updated information on historical trends and funding levels throughout the appropriations process as it pertains to global health. GHTC member PATH is developing the Innovative Countdown initiative to showcase the innovations the world believes have the greatest promise to accelerate progress and “bend the curve” of present trends to meet the United Nations’ Sustainable Development Goals health targets. To participate in the survey, click here. Claire Topal, senior advisor for international health at The National Bureau of Asian Research, interviewed Rob Lin from the Infectious Disease Research Institute on the value of product development partnerships (PDPs). Lin discusses how PDPs came about, what gaps PDPs currently fill in the development of new global health tools, the costs associated with development new health products, and the various collaborations PDPs are involved in to maximize the impact of their work.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Earlier this month, advocates from the Community Research Advisors Group (CRAG)—an international, community-based advisory body working to ensure the engagement of affected communities in tuberculosis (TB) research conducted by the Centers for Disease Control and Prevention—published an article in The Lancet offering a community perspective on the use of the drug bedaquiline to treat drug-resistant and drug-susceptible TB. The US Food and Drug Administration approved bedquiline for the treatment of drug-resistant TB—via an accelerated approval process—in December 2012, making it the first new drug from a novel class approved to treat TB in more than 40 years. Former chief scientist at the US Agency for International Development (USAID), Alex Dehgan, sat down with the Center for Global Development to talk about the new USAID Global Development Lab. Dehgan—who was a major architect of the Lab—said the Lab’s purpose is to “rethink assumptions and harness the power of the crowd and America’s leading research institutes and universities, coupled with the democratization of science and technology, to lead to new breakthroughs that it can bring to scale.” SciDev reports that only 86 of about 3,200 people in the “Highly Cited Researchers” list are living in developing countries. SciDev examined Thomson Reuters’ The World’s Most Influential Scientific Minds: 2014 report and found a significant North-South divide in recent citations of published papers across science. In sub-Saharan Africa, only researchers in South Africa were highly cited. Pharmaceutical company Novartis has signed a licensing agreement with GHTC member TB Alliance to advance drug development to fight TB. Novartis will transfer its TB research program to TB Alliance, which will “take financial and operational responsibility for continued research, development, approval and distribution of compounds in the portfolio.” With the world’s worst Ebola outbreak still not under control, the United Kingdom and the Wellcome Trust are pledging $10.8 million to launch an emergency research effort to help fight the disease. Experts from around the world have been asked to submit research proposals by September 8 that can quickly investigate new ways of treating, preventing, and containing Ebola.

Earlier this month, advocates from the Community Research Advisors Group (CRAG)—an international, community-based advisory body working to ensure the engagement of affected communities in tuberculosis (TB) research conducted by the Centers for Disease Control and Prevention (CDC) —published an article in The Lancet offering a community perspective on the use of the drug bedaquiline to treat drug-resistant and drug-susceptible TB. The US Food and Drug Administration (FDA) approved bedquiline for the treatment of drug-resistant tuberculosis—via an accelerated approval process—in December 2012, making it the first new drug from a novel class approved to treat TB in more than 40 years. Laia Ruiz Mingote and Dorothy Namutamba—co-chairs of CRAG— and Mike Watson Frick—TB/HIV Program Officer at GHTC member organization, Treatment Action Group—are among the article’s co-authors, and join us to answer questions about the article and discuss the benefits and risks of using bedaquiline to treat TB. Bedaquiline is the first new drug from a novel class approved to treat TB in more than 40 years. PATH/Katrina Peach Q: Bedaquiline has been shown to be effective in treating drug-resistant TB in combination with other drugs, but it also has some serious side-effects and risks. Explain what those are. In Phase II studies, bedaquiline showed promising activity against multidrug-resistant TB (MDR-TB). The drug reduced the average time to a negative TB culture from 18 to 12 weeks and increased the proportion of participants with a negative culture at 6 months from 58 percent to 79 percent. However, bedaquiline posed several safety concerns that should be addressed before testing the drug in people with drug-susceptible TB. Most attention has focused on bedaquiline’s association with QT prolongation—a potentially serious disturbance in the heart’s electrical rhythm. Other TB drugs also cause QT prolongation, including moxifloxacin and the other new MDR-TB drug, delamanid (developed by the company Ostuka). Other side effects of bedaquiline include liver toxicity, accumulation of phospholipids in cells, and even death. In one Phase II trial, a significantly higher number of participants receiving bedaquiline died than those receiving placebo. While these deaths did not have a common cause and occurred months after the trial, the FDA could not rule out the possibility that bedaquiline played a role. Since bedaquiline has a long half-life, meaning that it remains in the body for a long time, the drug may continue to pose a side effect risk to patients even after they stop taking it. Q: Given its side effects and risks, do you still believe bedaquiline merited accelerated approval by the FDA? Do you believe other countries should also approve bedaquiline’s use for drug-resistant TB? The accelerated approval was necessary. There are few effective treatment options for patients with MDR-TB and extensively drug-resistant TB (XDR-TB), and many of these patients are unable to tolerate existing options, as they also have strong side effects and risks of their own including hearing loss, neurological disturbances, and skin discoloration. However, there is a need for more information and clinical data to know how to manage the risks tied to bedaquiline. We have to make it clear that bedaquiline is not for all TB patients, but rather only for those people who are unable to tolerate other MDR-TB drugs to which their TB is susceptible or who might not survive without access to bedaquiline, as there are no other treatment options. In countries and regions with high incidence of drug-resistant TB, bedaquiline is a necessary and important addition to second- and third-line therapies. Yet most countries have been slow to approve bedaquiline, meaning that most patients can only access it through unreliable compassionate use mechanisms. Other countries, particularly those of the former Soviet Union, lack the legal frameworks that enable compassionate use. In countries with high incidence of drug-resistant TB, bedaquiline is an important addition to second- and third-line therapies. PATH/Nguyen Ba Quang Additionally, the high price of bedaquiline may discourage its use among patients who need it most. Janssen—the company that developed bedaquiline—has announced a tiered pricing scheme in which the price of bedaquiline varies depending on a country’s Gross National Income: high-income countries will pay about $30,000, middle-income countries will pay $3,600 and low-income countries will pay $900. Countries with the most severe MDR-TB epidemics are usually middle-income countries including South Africa, India, Russia, and China. While South Africa may be able to access the lowest price of bedaquiline, it’s unclear whether Janssen will extend the lower $900 price to other middle-income countries like China, where second-line TB drugs are not provided for free by the government. Can Chinese TB patients really afford bedaquiline at a price of $3,600? Even in high-income countries, the steep price of the drug can drain the general budget of TB programs, especially considering the high cost of other second-line drugs used to treat MDR-TB. Finally, in ensuring access to the treatment, Janssen must also make every effort to track safety and patient outcomes in people who receive bedaquiline. In the United States, a patient registry exists in theory, but many doctors do not know about the registry, and those who do have had difficulty enrolling patients into it. In the absence of a Phase III clinical trial of bedaquiline, patient registries may offer the best way to obtain additional safety data. Q: Clinical trial data on bedaquiline’s use for drug-resistant TB suggests it could also be effective in shortening treatment time for drug-susceptible TB as part of a first-line therapy combination. What are your concerns about the inclusion of bedaquiline in trials exploring its use for drug-susceptible TB? As mentioned, bedaquiline is a game changer in cases of MDR- and XDR-TB. However, for drug-susceptible TB, we have a well-established standard of care and other options for shortening treatment using existing drugs—such as rifapentine which is manufactured by Sanofi—or investigational drugs— such as PA-824 which was developed by the TB Alliance—that so far lack the safety signals observed in the Phase II trials of bedaquiline. The CDC’s Tuberculosis Trials Consortium will soon begin a Phase III study to see if replacing rifampicin with rifapentine can shorten drug-susceptible TB treatment from 6 to 4 months. The TB Alliance is also testing a 4-month drug-susceptible TB treatment regimen that uses a combination of PA-824, moxifloxacin, and pyrazinamide. Patients with drug-susceptible TB face a very different risk-benefit trade-off than people with drug-resistant TB. Currently, drug-susceptible TB has a safe and effective standard of care, although we agree that at six months, it is too long and there is the necessity to make it shorter. It is because of the safety of the regular regimen that, together with the current data, bedaquiline may not offer the best way forward for shortening drug-susceptible TB treatment. We believe that before studying bedaquiline for drug-susceptible TB, we need much more information about this new drug, its long-lasting presence in the body and common side effects. In addition, the use of bedaquiline in first line treatment could, in fact, risk an increase in resistance, leaving patients with fewer treatment options.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. This month, after nearly ten years of effort, the first batch of malaria drugs manufactured with a new, semisynthetic form of a key ingredient, artemisinin, will start reaching African countries battling the disease. The lifesaving drugs, manufactured by Sanofi—a French pharmaceutical company—are the first of their kind to use semisynthetic artemisinin in place of the plant-derived form of artemisinin used in the past. The new shipment marks a milestone in global health, potentially improving access to treatment for the millions of people, mostly African children, sickened by malaria every year. The Global Coalition to Advance Preterm Birth Research (GCAPR), a new partnership initiated by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the March of Dimes Foundation, the Bill & Melinda Gates Foundation, and GHTC member the Global Alliance to Prevent Prematurity and Stillbirth, has been created to take on the high rate of preterm births and help prevent the health risks associated with them. An estimated 15 million babies are born preterm every year and more than 1 million die within the first 30 days of birth. The National Institutes of Health’s National Institute of Allergy and Infectious Diseases has performed a successful early-stage clinical trial for a vaccine against mosquito-borne viral illness chikungunya. There are currently no vaccines or specific drugs to prevent or treat chikungunya, and as of this month there have been more than 570,000 confirmed or suspected cases reported throughout North and South America. The first-ever Africa Leaders Summit this month was a clear example that partnerships between the United States and African nations are strong and building momentum. The summit was a busy few days with a flurry of announcements, but the practical implications of the summit for global health innovation were examined by GHTC Policy Officer Ashley Bennett in a recent post on Breakthroughs. In The Huffington Post’s blog, Dr. Jonathan Mermin—director of the Center for Disease Control and Prevention’s National Center for HIV and AIDS, Viral Hepatitis, STD, and TB Prevention—writes about the need for new tools to fight tuberculosis (TB). He states, “Until we have better ways of detecting and treating TB, thousands of Americans and millions of people worldwide will continue to suffer from an illness that should have been consigned to history long ago.”