Breakthroughs Blog: Contraceptives

The zoonotic Middle East Respiratory Syndrome (MERS), which World Health Organization (WHO) Director-General Dr. Margaret Chan called “a threat to the entire world” has spread to South Korea. More than 100 cases and 10 deaths have been reported, making it the largest outbreak outside of the Arabian Peninsula. While there are currently no vaccines or treatments for MERS, researchers are confident that with adequate political will and funding, such products could be rapidly advanced. Photo: PATH/Nguyen Ba Quang Dr. Matthew Frieman, a professor and researcher at the University of Maryland School of Medicine, has developed an experimental vaccine in partnership with vaccine company Novavax Inc. that successfully protected mice against the MERS virus. Greffex, another vaccine company, has already worked with the US National Institute of Allergy and Infectious Diseases to develop a vaccine that triggers the production of antibodies—proteins that protect against the disease—in mice. Dr. Frieman and Greffex CEO John Price agree that funding and political will are the only barriers to the development of a MERS vaccine. According to Price, Greffex could develop a MERS vaccine candidate in less than a month with a sample of the virus, but they lack the funding to conduct clinical trials. Researchers have also struggled to obtain the needed information and materials—including samples of the virus—from scientists in Saudi Arabia. In the meantime, Frieman is working to test existing, approved drugs for the treatment of MERS, and has identified 27 drugs that have demonstrated potential in combatting MERS in a laboratory setting. At this year’s G7 summit, leaders of seven countries—including Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States— pledged to advance research and development (R&D) for neglected tropical diseases and new antibiotics. The members of the G7 committed to supporting everything from basic research through the development of “easily usable and affordable drugs, vaccines and point-of-care [diagnostics].” The G7 Leaders' Declaration also endorses the WHO Global Action Plan on Antimicrobial Resistance and the WHO Global Observatory on Health Research and Development, highlighting the need for improved coordination of global health R&D. In a New York Times op-ed, Gregg Gonsalves and Mark Harrington, co-founders of the Treatment Action Group, reflected on lessons learned about the US Food and Drug Administration’s (FDA) drug approval process during the US HIV and AIDS epidemic. The article comes as Congress is considering the 21st Century Cures Act, a bill intended to advance medical breakthroughs, in part through FDA reform. The legislation includes several provisions to expedite the approval of drugs and medical devices based on what Gonsalves and Harrington consider to be “lower standards.” The authors assert that while innovative regulatory pathways—such as the Accelerated Approval Program—enabled early access to new HIV and AIDS drugs, pharmaceutical companies were still required to demonstrate the safety and efficacy of products before they entered the market. Additionally, in the case of preliminary approval, companies were expected to continue and complete clinical trials. To protect patient safety, Gonsalves and Harrington argue that such standards should be upheld, reminding Congress that those standards “paved the way for the development and approval of breakthrough drugs [that] have been proven to be effective and safe.” There are nearly 170 contraceptives products in the R&D pipeline, from discovery, through product development, to regulatory review. Researchers, advocates, funders, and procurement agencies can now find information about these products all in one place through Calliope, the Contraceptive Pipeline Database, a new resource developed by GHTC member FHI 360. Calliope includes information regarding the R&D stage, the partners, the active pharmaceutical ingredients, the delivery and duration, and the mechanism by which the technologies prevent pregnancy. The contraceptive pipeline is diverse, and includes vaccines, microbicides, implants intrauterine devices and balls, pills, and even microchips. The exchange was created to galvanize contraceptive R&D for low-resource settings through knowledge sharing and the facilitation of cross-sector partnerships.

[Editor's note 4/1/16:The Global Health Regulatory Requirements Database is no longer part of GHTC. The global health regulatory team's member site is now hosted on the Gates Foundation PDP forum.] Photo: FDA/Michael J. Ermarth Navigating global regulatory processes is a critical component to the development and introduction of global health technologies. New drugs, vaccines, medical devices, and diagnostics must be evaluated and registered by national regulatory authorities before they can reach patients who need them. These technologies are typically intended for use in low- and middle-income countries (LMICs) which often have limited regulatory capacity and evolving regulatory requirements. As a result, securing clinical trial and product registration approval from national regulatory authorities can be a considerable hurdle for product developers. The GHTC’s Global Health Regulatory Requirements Database, developed with support from the Bill & Melinda Gates Foundation, is a tool that helps product developers and global health advocates better understand and navigate regulatory requirements of LMICs. The database serves as a critical information tool to help facilitate the testing and launch of new, lifesaving global health technologies. Here are four reasons why you should check it out: 1. It’s easy to use. Organized by country and technology type, the database features high-level summaries of regulatory requirements for 25 countries in Africa, Asia, Europe, and Latin America. The database conveniently consolidates regulatory requirements for these countries in one place, so users don't have to spend as much time tracking down regulatory information for different countries. Think of it as Cliff Notes for global health regulatory processes. 2. It’s comprehensive, but still comprehensible. Users can access top-line information on regulatory authority structure, relevant harmonization initiatives, ethics review processes, clinical trial and product registration application requirements, and pharmacovigilance requirements. You can also find links to key guidances and other relevant resources. All the information is presented in an easy-to-scan format so you can find what you seek. 3. It’s regularly updated. In August 2014, the Global Health Technologies Coalition (GHTC) completed its annual verification of the database. All information in the database is systematically reviewed on an annual basis, and significant changes to country regulatory requirements also are added on an ad-hoc basis. 4. It’s constantly expanding. During the last year, the GHTC introduced eight new countries to the database—Bangladesh, Ghana, Malawi, Malaysia, Nepal, Peru, Russia, and Ukraine! The GHTC also recently added country-specific labeling requirements and expanded information on regulatory authority collaborations with the World Health Organization and stringent regulatory authorities like the US Food and Drug Administration and European Medicines Agency. Whether you are a global health product developer or an advocate, you’ll find the database to be a useful tool. It can help product developers access necessary information to formulate a regulatory strategy, and can help advocates identify areas to provide and champion technical assistance for capacity development, harmonization, and other ways to advance global regulatory processes.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Last week, Deutsche Stiftung Weltbevoelkerung (DSW) attended the seventh European & Developing Countries Clinical Trial Partnership (EDCTP) Forum in Berlin, Germany. Anne Hradský—advocacy coordinator at DSW—writes about the value of EDCTP, the progress it has achieved, and news and insights that came out of this year’s forum. The Lancet has published results for the first-ever large-scale Phase III clinical trial for a vaccine against dengue fever. The results show that the three-dose vaccine could reduce cases of dengue fever by 56.5 percent and dengue hemorrhagic fever—a more severe form of dengue—by up to 88.5 percent. The vaccine is being developed by pharmaceutical company Sanofi Pasteur. A new form of easy-to-use injectable contraceptive Depo-Provera—called Sayana® Press—was introduced in Burkina Faso last week as part of a four-country rollout this year. The new form uses PATH-developed Uniject™—an autodisable injection system involving a plastic bubble with a needle attached and filled with one dose of the contraceptive. The device will be introduced next in Uganda, Senegal, and Niger. The Global Post has published the first article in a special report examining how US-backed public-private partnerships (PPPs) are making an impact on global health and whether there is evidence justifying increased US investment in PPPs, especially by the US Agency for International Development. Leaders of the biopharmaceutical research community called on Congress to improve the clinical research process to accelerate the discovery and development of new medical therapies. The 21st Century Cures Initiative—part of the House Energy & Commerce Committee—asked experts to present “strategies for reducing regulatory oversight, speeding up clinical research processes, and utilizing technology to better understand the potential benefits and risks of promising new treatments.”

Tomorrow US policymakers and global health advocates will come together to talk progress made on preventing maternal and child deaths. During the day, the US Agency for International Development (USAID) will host a high-level forum called Acting on the Call: Ending Preventable Child and Maternal Deaths to both celebrate progress and assess the challenges that remain. That evening, the 5th Birthday and Beyond coalition will celebrate America’s leadership and investments worldwide to help children reach their fifth birthday. US investment in R&D has led to new innovations that are saving the lives of mothers and children. Photo: PATH/Teresa Guillien While you’ll probably hear a lot of different facts and figures, one message will be clear—the world has made remarkable progress in preventing the deaths of millions of women and children. In fact, maternal and child deaths have been cut in half in just over two decades. That means that every day this year, 17,000 more children will live and 700 more mothers will survive childbirth than did two decades ago. Central to this progress has been US investment in research and development (R&D) that has led to new medicines and innovative health products that are saving the lives of mothers and children. Globally new vaccines, drugs, diagnostics, and other health innovations have led to 4.2 million fewer child deaths in 2013 compared to 1990, according to a report by the Institute for Health Metrics and Evaluation. Innovations like the polio vaccine, oral rehydration solution to treat diarrhea, and antiretroviral therapies that prevent maternal to child HIV transfer, and others treatments have resulted in incredible gains for maternal and child health.   No country has done more than the United States to help save the lives of the world’s poorest mothers and children. A critical part of the US approach has been our world-leading investment in global health R&D. In fact, the US government is the largest funder of global heath R&D in the world—contributing over 45 percent of total investment. US government investment in global health R&D has led to breakthroughs that have transformed or are poised to transform efforts to reduce maternal and child mortality. Some examples include: The Oxytocin-Uniject™ This is a device filled with oxytocin that helps contract the uterus to reduce post-partum hemorrhage—or excessive bleeding—the leading cause of maternal death worldwide. It is easy to inject and requires little training to administer, so it’s made a dramatic difference in the ability of health workers to administer oxytocin in emergencies or in remote locations outside of traditional hospital facilities. USAID played a crucial role in funding research towards the development of this product. RTS,S malaria vaccine candidate RTS,S is the most clinically-advanced vaccine candidate for malaria—a disease which kills a child every 40 seconds. A recent study showed that infants who receive the RTS, S vaccine had one third fewer cases of both clinical and severe malaria. A vaccine could be an important tool in reducing child sickness and death from malaria. The Department of Defense provided critical funding for the early development and clinical testing of RTS,S. Rotavirus vaccines Rotavirus-induced diarrheal disease kills roughly 435,000 children younger than five each year. Two currently available rotavirus vaccines were introduced in the past two decades, with other vaccines under development showing tremendous progress. The National Institutes of Health developed the first available rotavirus vaccine and has been a financial partner in the development of subsequent vaccines. In addition, the Centers for Disease Control and Prevention also monitors efficacy and safety, and supports clinical trials of rotavirus vaccines. New contraceptive technologies Family planning technologies allow women to space their pregnancies—making it more likely for both the mother and child to survive childbirth. An analysis of 172 countries found that family planning prevented 272,000 maternal deaths in just one year. However, the contraceptive options that exist today don’t always meet the needs of women in developing countries. New vaginal rings are being developed that will be long-lasting and easy for the user to insert and remove without a doctor’s assistance, while new multipurpose prevention technologies combine the delivery of contraceptives with microbicides which reduce the transmission of HIV and other sexually transmitted infections. USAID provides funding towards the development of many of these new contraceptive technologies. While tremendous progress has been made in decreasing maternal and child deaths worldwide thanks in part to new health innovations, each year 6.6 million children still die before their first birthday and 289,000 women still die from pregnancy-related causes. That translates to 18,000 children under the age of five and 800 pregnant women or women in childbirth dying every single day. The United States can and must do more. While the United States should increase access to proven and existing drugs, vaccines, and other health tools for maternal and child health, it is just as critical to develop the next generation of tools to prevent and treat existing and emerging diseases. Sustained and continued investment by the US government in global health R&D is critical to ending maternal and child deaths.