Breakthroughs Blog: Contraceptives

It’s that time of year when Americans join together with family and friends and give thanks for the many things in life for which they are most grateful. In the spirit of the Thanksgiving holiday, GHTC asked our members and staff to share what they are most thankful for in global health. Here’s what they had to say: “I am thankful for all patients who take part in clinical trials so that the world will have more effective regimens to end TB, in all its forms.” Willo Brock, Senior Vice President of External Affairs, TB Alliance “I’m thankful there is increasing global interest in the development and production of vaccines for diseases of poverty, like hookworm, schistosomiasis, and Chagas.” Tara Bracken, Communications Associate, Sabin Vaccine Institute “I am thankful that 2016 was a turning point for women’s HIV prevention research—one that brought us hope for one day soon expanding women’s options with a long-acting vaginal ring. I am also grateful for the amazing partners who believe women’s health and empowerment matter!” Zeda Rosenberg, Founder and CEO, International Partnership for Microbicides “I’m thankful for the new generation of emerging R&D leaders who are both generating new knowledge and achieving global health impact.” Dr. Timothy Mastro, Chief Science Officer, FHI 360 “I’m thankful for sustained US government funding to fight emerging epidemics, like Ebola and Zika, through R&D and scientific advancement.” Lindsay Litwin, Jhpiego Innovations “I’m thankful that elimination of sleeping sickness is now a real possibility thanks to new tests being strategically implemented alongside new vector control technologies and improved treatment regimens.” Dr. Joseph Ndung’u, Head of Neglected Tropical Diseases Programme, FIND “I’m thankful that the six antimalarials MMV and partners have brought forward are saving young lives today!” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful for research that has shown promise for an effective six-month regimen to cure XDR-TB [extensively drug-resistant TB].” Rabita Aziz, Policy Research Coordinator, ISDA Global Health “I’m thankful for the inspirational dedication and continued participation of all HIV vaccine clinical trial volunteers. Without you, the important work of finding a safe and effective HIV vaccine would not be possible.” Dr. Fran Priddy, Chief Medical Officer, International AIDS Vaccine Initiative “I’m thankful for the over 200 members of Congress who have co-sponsored the Reach Act to accelerate efforts to end preventable deaths of mothers and children around the world.” Brandon Ball, Policy and Advocacy Officer, PATH "I'm thankful for low-cost interventions like chlorhexidine gel for umbilical cord care being made more accessible to Sub-Saharan Africa to reduce newborn mortality." Assumpta Nantume, Communications Associate/Global Health Corps Fellow, Global Health Council “I'm thankful a new generation of Middle Eastern scientists are advancing the development, production, and characterization of new vaccines to help endemic countries better respond to the threat of infectious diseases like MERS, schistosomiasis, and leishmaniasis.” Chris Bennett, Senior Program Officer, Sabin Vaccine Institute “I’m thankful for pioneering donors such as UNITAID for funding development of new hepatitis C tests for countries where fewer than 1 percent of people living with hepatitis C have been diagnosed.” Catharina Boehme, Chief Executive Officer, FIND “I’m thankful for scientists and researchers who devote their lives to important global infectious disease work to help people around the world and to protect Americans here at home and the funding the US government provides for such important work.” Karen Goraleski, Executive Director, American Society for Tropical Medicine and Hygiene “I’m thankful for the tremendous progress we’ve made in advancing child and maternal survival and excited for the prospect of saving the lives of more than 6 million mothers and children by 2030 if we work together to advance and scale-up 11 promising innovations.” Heather Ignatius, Multilateral, US, and Europe Policy & Advocacy Team Lead, PATH “I’m thankful for researchers across the globe whose efforts have, with unprecedented speed, deepened our scientific understanding of and advanced new tools to prevent, detect, and treat Zika.” Kat Kelley, Senior Program Assistant, GHTC “I'm thankful so many good dengue vaccine candidates are in development that could help curb the growing global dengue epidemic.” Tara Bracken, Communications Associate, Sabin Vaccine Institute "I'm thankful for increased awareness on global antibiotic resistance and WHO's new evidence-based Infection Prevention and Control Guidelines." Danielle Heiberg, Advocacy Manager, Global Health Council “I'm thankful for the lives of mothers and babies that have been saved, sustained, and supported by midwives across the globe.” Shannon Egan, Jhpiego Innovations “I’m thankful that malaria rapid tests have contributed to better malaria control, which in turn has helped fuel a massive decline in childhood mortality over the past decade—and that partners around the world are working together to find innovative new solutions for identifying non-malarial causes of fever. Diagnosis matters!” Dr. Iveth J. González, Head of Malaria and Acute Febrile Syndrome programme, FIND “I’m thankful for the support of MMV’s committed donors and partners that make our work to develop new antimalarials for vulnerable populations possible.” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful to be a part of the #StartStayAIDSFree initiative which aims to end AIDS in children by 2020.” Catherine Connor, Senior Director of Public Policy and Advocacy, Elizabeth Glaser Pediatric AIDS Foundation “I’m thankful that members of both major US political parties have continued to demonstrate strong, bipartisan support for global health research and development and US efforts to save lives around the world.” Marissa Chmiola, Communications Officer, GHTC

This International Women’s Day, GHTC is celebrating two novel, female-initiated health technologies that have the potential to give women and girls greater control over their sexual and reproductive health, empowering them to make informed decisions about whether and when to have children and to protect themselves and their families from HIV and other sexually transmitted infections (STIs). The Women’s Condom. Photo: PATH/Glenn Austin This International Women’s Day, GHTC is celebrating two novel, female-initiated health technologies that have the potential to give women and girls greater control over their sexual and reproductive health, empowering them to make informed decisions about whether and when to have children and to protect themselves and their families from HIV and other sexually transmitted infections (STIs). GHTC members PATH and the International Partnership for Microbicides (IPM) both recently announced exciting milestones in developing and expanding access to game-changing contraceptive and HIV/STI prevention tools that help women negotiate safer sex. The Woman’s Condom, manufactured by Shanghai Dahua Medical Apparatus Co., Ltd, (DAHUA) and marketed under various brand names including O’Lavie, received World Health Organization (WHO)/United Nations Population Fund (UNFPA) prequalification last week. This approval opens the door for its purchase and distribution by United Nations (UN) agencies and other leading international organizations for distribution in the public sector. And just the week before, IPM announced the results of two large Phase 3 clinical trials—The Ring Study and ASPIRE—which showed that a monthly vaginal ring containing the antiretroviral drug (ARV) dapivirine, developed by IPM, can safely help protect women from HIV. Enduring unmet need for family planning and HIV/STI prevention methods Globally, an estimated 225 million women have an unmet need for family planning and more than 350 million new cases of curable STIs occur every year. Women's and adolescent girls' contraceptive and HIV/STI prevention needs vary across geographies and cultures and often change throughout a woman’s life. Therefore, unmet need can only be addressed through ensuring access to a range of contraceptive options. When women and adolescent girls make contraceptive decisions, they have a lot to consider: Cost Efficacy Ease of use Side effects, health concerns, and whether a hormonal or non-hormonal option is right for them Ease of access, including how often they’d have to visit a health clinic or pharmacy and the reliability of the supply of in their community Stigma(s) surrounding contraceptive use and whether they can discreetly access contraceptives Comfort and whether the product impacts pleasure during intercourse Whether they can use or administer the contraceptive themselves or must rely on a health worker or partner. Biologically and as a result of gender-based violence and discrimination, women and girls are at greater risk for HIV infection. In sub-Saharan Africa, women aged 15 to 24 are twice as likely to become infected with HIV compared to their male peers. And often, women are not empowered to negotiate safe sex with their partners, particularly the use of male condoms. The prevention methods currently available aren’t doing enough to stop the alarming rates of infection in women in sub-Saharan Africa and are often unrealistic options for them. What makes these tools so game-changing for women? The Woman’s Condom and the dapivirine ring put the power of protection in the hands of women. The Woman’s Condom was developed by PATH, CONRAD, and other partners through a user-centered design process across four countries. “This iterative process enabled the partners to create a product that truly met the needs of women and couples. The Woman’s Condom is easy to insert, use and remove; stays in place during intercourse; and is comfortable, providing good sensation for both partners,” said Patricia Coffey, head of PATH’s Health Technologies for Women and Children Team. “Unlike other female condoms on the market, the Woman’s Condom’s main pouch is compressed into a narrow, rounded capsule which women insert like a tampon. And importantly, women can insert it themselves, without relying on their partner’s cooperation. It provides another option in cases where a male partner won’t use a male condom, and it also enables a woman to bring something to the relationship…it gives the woman a chance to take a more proactive role in protecting herself and her partner,” said Coffey. The dapivirine ring (Photo: International Partnership for Microbicides) The dapivirine ring is the first long-acting HIV prevention method designed for women. It adapts a medical device commonly used to deliver hormones to women—the vaginal ring—to deliver an ARV drug. The ring is easy for a woman to insert and remove herself, can be left in for one month, and used without the knowledge of a sexual partner. In two large Phase 3 clinical trials across four countries in sub-Saharan Africa, the ring was shown to reduce HIV infection rates by 31 and 27 percent overall. This is the first time two Phase 3 studies have confirmed statistically significant efficacy for a microbicide to prevent HIV. The studies found differences in efficacy by age and level of use: For women over 21, who appeared to use the ring more consistently, the ring reduced infection by 37 and 56 percent. The dapivirine ring could “give new hope to many women at high risk who need more and different options to effectively protect themselves from HIV,” according to IPM Founding Chief Executive Officer Dr. Zeda Rosenberg. “We are also hopeful we can learn more about how to help women who want to use the ring do so consistently, which could help increase protection.” What do these announcements mean for access to these innovative new tools? WHO/UNFPA prequalification represents an important step in increasing access to the Woman’s Condom, which is currently approved for use in China, Europe, Malawi, South Africa, and Zambia. Prequalification serves as an endorsement of quality, efficacy, and safety, particularly for nations with limited regulatory capacity. It not only enables UN agencies to procure the Woman’s Condom, but the US Agency for International Development—one of the largest female condom procurers worldwide—could rely on WHO prequalification, when a product has not been reviewed by the US Food and Drug Administration. Introduction of the Woman’s Condom in new countries could also further grow the market for female condoms broadly. Because of its innovative insertion design, the Woman’s Condom has proven popular among users and some have even called the product “elegant” and “beautiful,” according to Coffey. Thus, the Woman’s Condom could help attract new users to the female condom product category and help normalize and increase regular and consistent use of female condoms. The results from the two dapivirine ring trials are a significant step forward to getting an affordable microbicide ring into the hands of women who can benefit from it. Next, IPM will submit the dapivirine ring for regulatory review while simultaneously working with partners and governments to determine how the product can best strengthen HIV prevention efforts. IPM also plans to conduct an open-label extension (OLE) study that would provide former Ring Study participants with access to the dapivirine ring and enable IPM to collect additional information on its safety and efficacy. Such a study could help IPM better understand real-world use of the dapivirine ring, and awareness of the ring’s safety and efficacy could increase adherence among participants, as was seen in follow-up OLEs of oral pre-exposure prophylaxis. The trial results also open the door to next-generation prevention products. IPM has several other microbicide products in the pipeline, including vaginal rings combining dapivirine with other ARVs and a vaginal ring containing dapivirine and a contraceptive hormone, which would last for three months and prevent both unintended pregnancy and HIV. The combination ARV rings are in Phase 1 and preclinical development, and the dapivirine-contraceptive ring is expected to enter a Phase I trial later this year.

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.

Photo credit: TB Alliance GHTC member TB Alliance announced last week the creation of the first-ever child-friendly tuberculosis (TB) medicines, which are currently undergoing regulatory review by the World Health Organization and should be available in early 2016. While TB is curable, a patient must take multiple drugs a day for six months, and existing medicines are not available in appropriate doses for children. Consequently, parents must crush or cut the pills. This arduous process—combined with the bitter taste—makes the six-month regimen difficult to follow. The new treatment is comprised of strawberry- and raspberry-flavored, child-friendly doses of the three most commonly used TB medicines. The new regimen is expected to significantly enhance adherence to treatment for the 1 million children diagnosed with TB each year. Researchers at Texas A&M University have developed a device that, when attached to a smartphone, can diagnose malaria in minutes. Using a polarized light and the phone’s camera, the device serves as a microscope. The photos taken by the device are then analyzed by a software app that diagnoses infection by counting both red blood cells and Hemozoin crystals, which are produced by the malaria parasite. The device, which is expected to cost less than US$50 and be used with cartridges costing $1 each, will be tested in Rwanda next summer. A preclinical study conducted by GHTC member Population Council in partnership with CONRAD suggests that candidate microbicide gel MZC could be even more effective against HIV than tenofovir gel, a leading microbicide candidate. Containing a potent antiretroviral, a zinc-based salt, and the compound carrageenan, the gel is intended to protect against HIV, human papillomavirus (HPV), and herpes simplex virus 2 (HSV-2). The study demonstrated that MZC was more potent than tenofovir against both HIV and HSV-2. While the study did not test the gel’s efficacy against HPV, existing research suggests that carrageenan is one of the most potent compounds against HPV. Next, MZC will be tested in delivery systems, including vaginal rings and rectal gels, as well as in combination with a hormonal contraceptive. In other microbicide news, GHTC Member the International Partnership for Microbicides (IPM) has entered an agreement with pharmaceutical company Janssen Sciences that provides IPM the rights to develop a microbicide using the antiretroviral darunavir, which is currently available in pill form and marketed as PREZISTA®. IPM is also conducting a phase III clinical trial of a vaginal ring using antiretroviral dapirivine, licensed to the organization through a partnership with Janssen initiated in 2004.