Breakthroughs Blog: Microbicides

Photo: CDC/ Dr. Mae Melvin A recently released clinical report from the US Centers for Disease Control and Prevention details a case of a Colombian man who developed cancerous tumors on his lungs and liver that were comprised of tapeworm cells, rather than human cells. An estimated 75 million people are infected by Hymenolepis nana, the most common human tapeworm, however, this is the first reported case of cancer spreading across species to humans. The team suspects that the tapeworm vector did not have cancer, but rather that one of its eggs mutated within the patient’s gut into cancerous cells. International Partnership for Microbicides (IPM), a member of the GHTC, is conducting Phase I clinical trials of a novel HIV and AIDS prevention method known as DS003. The drug binds to a protein on the surface of the HIV virus, preventing it from entering human immune cells. The trial will involve three stages, during which nine women will receive the drug and three will receive a placebo, enrolling 36 volunteers in total. At each stage, the participants will receive increasingly higher doses, from 1 to 10 mg, assuming that the previous stage demonstrated the drug to be safe and tolerable. The drug will be tested as a vaginal tablet, and if successful, DS003 will likely be tested in vaginal rings and/or in combination with other antiretroviral drugs. The fastest and most accurate tuberculosis (TB) diagnostic test will soon be available as a portable and more affordable device, making it more accessible in low-resource settings. Cepheid Inc.’s GeneXpert was endorsed by the World Health Organization in 2010, and its use increases the accuracy of diagnosis by 39 percent, however, the machine costs US$17,000 and requires electricity, refrigeration, and access to a computer. The new GeneXpert Omni will be rolled out early next year at a fraction of the cost—$2,895 for the machine and $10 per cartridge. The Omni runs on a battery and connects to a smartphone, weighs just 2.2 pounds, and can diagnose drug-resistant TB along with 23 other diseases.

Photo: CDC/ Hsi Liu, Ph.D., MBA; James Gathany The US Department of Health and Human Services (HHS) announced last week a partnership with pharmaceutical company AstraZeneca for the research and development (R&D) of antibiotics. Through its Biomedical Advanced Research and Development Authority (BARDA), HHS will invest an initial US$50 million and up to $170 million into the project over five years. BARDA and AstraZeneca will meet annually to update their portfolio of drug candidates, determining which projects to initiate, continue, or terminate. The first project will be the advanced development and, ideally, regulatory approval of a treatment comprised of two existing antibiotics—Aztreonam and Avibactam—which is currently undergoing phase 2 clinical trials. The partners will also test new and existing antibiotics for use against diseases considered to be leading bioterrorism threats. Last Tuesday, US President Barack Obama nominated Dr. Robert Califf to lead the US Food and Drug Administration (FDA), where he has been serving as deputy commissioner for medical products and tobacco since January. Califf is a cardiologist and researcher, and previously served as the director of the Duke Translational Medicine Institute—which advances R&D by facilitating cross-sector partnerships—and as founding director of the Duke Clinical Research Institute. If confirmed by the Senate, Califf will succeed Dr. Stephen Ostroff who has served as acting commissioner since former Commissioner Dr. Margaret Hamburg announced her resignation in February. After joining the FDA in January, Califf announced that streamlining the clinical trial process would be a major focus during his tenure. A new analysis in the Guttmacher Policy Review calls for increased US investment in multipurpose prevention technologies (MPTs)—products that protect against multiple risks, including unintended pregnancy, HIV and AIDS, and other sexually transmitted infections (STIs). There is currently only one MPT in phase 3 clinical trials—a female condom that prevents pregnancy, HIV and AIDS, and four STIs—as well as nine in phase 1 trials, and thirteen in preclinical development. Among these MPTs are female condoms and vaginal rings, gels, films, nanofibers, and tablets. As MPTs are primarily intended for use in low-resource settings, private-sector interest has remained low. Additional, non-financial barriers to MPT R&D include scientific and regulatory hurdles: most MPTs have two or more active ingredients, and could thus be subject to review by as many as three divisions within the FDA. The report notes that the US government is already the biggest funder of MPT R&D, accounting for 89 percent of the $6.5 million invested in MPTs in 2013. New Delhi, India, is currently experiencing the worst outbreak of dengue fever it has seen since 2010, with nearly 1,900 confirmed cases this year. All four of the known strains of dengue virus are present in India, however, new evidence from the All India Institute of Medical Science (AIIMS) suggests that a fifth, previously undetected strain of the dengue virus, may be partially to blame for the severity of this year’s outbreak. Recovery from dengue fever provides lifetime immunity against the specific strain, however, the introduction of a new strain would leave the entire population vulnerable. AIIMS recorded the potential new strain after testing an initial fifty samples from recent dengue patients and is working with the Indian Ministry of Health and Family Welfare to collect and test more samples before coming to a conclusion.

New tools are needed to prevent HIV and AIDS, particularly among at-risk women. Photo: PATH/Gabe Bienczycki Sitting halfway around the world from my office in Washington, DC, looking out my Durban hotel window at the Indian Ocean, I am reminded just how small and interconnected our world really is. While home is a 24-hour journey from here, international travel is easy now. Like people, infectious diseases also move easily around the globe. As advocates gathered from across geographies, we are here in Durban to discuss research and development for new tools in the fight against HIV and AIDS. The excitement in our discussions is palpable as we think about where we have come in the HIV and AIDS epidemic to date, but also guarded as we look ahead to the daunting task of ending the epidemic forever. I traveled to Durban to participate in a partners meeting with the International Partnership for Microbicides (IPM). IPM, a GHTC member, is leading an exciting Phase III clinical trial program to determine if a new monthly vaginal ring it developed can prevent women from becoming infected with HIV and is safe for long-term use. The ring contains the antiretroviral (ARV) drug dapivirine, which is a new drug but part of the same class of ARVs currently in use for HIV and AIDS treatment. Initial efficacy results are expected as early next year. Dapivirine ring. Photo: IPM Throughout the meeting one thing became clear to me: we need new tools to combat the HIV and AIDS epidemic in South Africa, in Washington, DC, and everywhere in between. ARV treatment has helped save millions of lives. For the most part, people on treatment can live healthy and productive lives. That is, of course, if they have access to the medications they need, if they can take these medications daily, if they can keep regularly scheduled appointments with a health care provider, and perhaps most importantly, if they know they are infected in the first place. That’s a lot of ifs. What if we could prevent more infections in the first place? The new post-2015 development agenda about to be solidified by the United Nations later this month sets out to end the HIV and AIDS epidemic by 2030. This is a lofty goal that has policymakers and funders excited, but it should be regarded with caution as we look to the work that needs to be done. Truvada. Photo: CDC In the United States, the US Food and Drug Administration has approved the use of the ARV drug Truvada as a pre-exposure prophylaxis (known as PrEP) to prevent HIV infection among individuals who are determined to be at high risk for contracting HIV. PrEP is not yet approved for use in South Africa despite Truvada being an approved—and commonly used—drug for HIV and AIDS treatment. Why PrEP hasn’t been approved for use yet in South Africa is a complicated story, but unfortunately one that seems to haunt us in the global health advocacy community. All too often, we know what needs to be done to treat or prevent an infection, to save a mother’s life during childbirth, to keep a child alive during the most vulnerable early years of life, but politics keeps us from making progress. The stigma associated with HIV and AIDS is still real for women and men around the world. In the United States, it doesn’t help when we hear politicians talk about cutting funding for HIV and AIDS research because it doesn’t affect enough Americans anymore. Yes, we know how to treat people living with the disease, and yes, we know how to prevent mother-to-child HIV transmission, and yes, we even know how to prevent HIV infection in adults, but the reality is that politics are getting in the way. If we know how to save lives, it should not matter how policymakers personally feel about the way a disease is transmitted or the lifestyle of the populations most at risk for contracting a disease. Logic says that science should win this debate, but unfortunately, that is not the reality. To combat both the disease itself and a challenging global political environment, we need to keep our options open as we think about the tools we have and the tools that are needed to fight HIV and AIDS. We need to have an arsenal of tools that can be used safely and sometimes discretely by the people most at risk. IPM's monthly dapivirine ring has the potential to help women take more control over their health and reduce their risk. Too many women cannot negotiate the use of condoms (male or female) with their partners and therefore cannot be in control of their own HIV prevention. Developing and providing new options—like the dapivirine ring—that women could use as personal protection is essential. Further, we don’t just need to develop tools for the sake of new tools—we need to ensure that women and men have access to the most effective, affordable, and appropriate tools to address their health needs. I was fortunate to be able to accompany IPM and other partners on a visit to Qhakaza Mbokodo in Lady Smith, South Africa—one of the research clinics conducting IPM's Ring Study, which is one of two Phase III trials evaluating the ring. While there, I met an engaged and dedicated staff who have integrated themselves into a local community and really gotten to know the women who are participating in the trial. Women joined the trial voluntarily, many of them expressing an interest in helping to end a disease that is devastating their community or has killed a family member. They understand the potential risks associated with testing a new tool, and they know it might not be effective. But like me, as an advocate dedicated to preventing HIV, ending infectious disease epidemics, and empowering women to take control of their own health, they are all hopeful that the ring can be an effective tool to help us in the fight. We cannot end the HIV and AIDS epidemic with the current tools we have, and no one tool used alone—not PrEP, not the dapivirine ring, not condoms, not male circumcision—will get us to this goal. We need to have a comprehensive approach to the fight that involves both prevention and treatment. IPM's dapivirine ring program, regardless of the results, will teach us a lot about what works and what doesn’t. This is the way we must combat global health threats: with scientific rigor, with international partnership, and with robust investment in new tools. Erin Will Morton is GHTC’s Director

We have many reasons to be thankful. Photo: Satya Murthy As global health advocates, our work often requires us to focus on unmet needs—such as the number of people worldwide who still die from preventable diseases each year, or the lack of adequate resources and investment to tackle these diseases. Yet with Thanksgiving just around the corner, there is much for which we, as global health advocates, can be grateful in terms of advancements achieved in the development and deployment of lifesaving global health technologies. In the spirit of the holiday, here is my list of ten global health advancements I’m thankful for this Thanksgiving: After years of slow progress in the development of drugs, vaccines, and diagnostic tools to fight Ebola, efforts are now moving at hyper speed. Several experimental treatments and vaccines are now being tested in clinical trials in Ebola-endemic countries. Thanks to the development and widespread implementation of effective vaccines, this year the world moved one step closer to the eradication of polio. Scientists from the US Centers for Disease Control and Prevention believe that the second of three forms of poliovirus has successfully been eradicated. The first vaccine against hookworm has been shown to be safe in early-stage clinical trials. An effective vaccine could protect the more than 600 million people infected with this dangerous parasite worldwide. Widespread access to and use of antiretroviral therapy (ART) is fueling incredible progress in the fight against HIV and AIDS. According to the UNAIDS 2014 report, 2013 saw the lowest level of new HIV infections this century and the lowest number of AIDS-related deaths since 2005. As of this summer, nearly 14 million people are accessing ART. The world could soon have an important new tool in the first against dengue fever. Results from the second Phase III trial of the first vaccine candidate against dengue fever showed the vaccine to decrease incidences of dengue fever by nearly 60 percent. Within a few years, women could have new, user-friendly options to protect themselves against HIV. Several new antimicrobial vaginal gels and antiretroviral-releasing contraceptive vaginal rings are currently undergoing clinical trials. Significant progress has been achieved this year towards the development of new tools to fight malaria. After receiving expedited regulatory approval from the US Food and Drug Administration last year, new malaria drug treatment candidate tafenoquine entered Phase III trials this year. Additionally, the malaria vaccine candidate RTS,S is now under regulatory review by the European Medicines Agency. New pediatric drug formulations to treat tuberculosis (TB) could be available as early as late next year, according to developers. This advancement is critical as there is currently no appropriately dosed, child-friendly TB treatment available. New vaccines, drugs, diagnostics, and other health innovations have led to 4.2 million fewer child deaths globally last year compared to 1990. There are 365 global health products in the research pipeline that have the potential to fuel incredible gains in health for people around the world. With so much accomplished in 2014 and so many promising tools on the cusp of development and delivery, we have much to be thankful for this Thanksgiving. This Thursday, enjoy your Turkey and fixings with family and friends and give thanks for the incredible progress we’ve achieved this year. And then next week, when our turkey hangovers pass, we’ll get back to work.