Breakthroughs Blog: Guest post

Heather Ignatius is the senior policy manager for the TB Alliance, a not-for-profit, product development partnership dedicated to discovering, developing, and ensuring access to better, faster-acting, and affordable drugs to fight tuberculosis (TB) and drug-resistant TB. She is also a member of the GHTC’s Steering Committee. The most recent WHO TB Control report noted that rates of TB declined this past year for the first time in decades. However, even with such progress, TB remains one of the most devastating global health crises today, with ripple effects that extend beyond health to cripple prosperity and development of regions overwhelmed by the disease. New and improved tools to prevent, diagnose, and treat TB in its many forms—including MDR-TB and XDR-TB—are vital to eradicate the disease, but a reinvention of such an arsenal can’t be achieved by any single organization. To this end, last week marked another notable achievement for TB: the launch of a collaboration between four pharmaceutical companies, along with the TB Alliance and the World Health Organization (WHO), which enables information-sharing on TB drug candidates within their respective pipelines. The partnership aims to bring these groups together to quickly and collaboratively identify and develop the most promising new TB drug regimens, regardless of sponsor. Representatives from (left to right) TB Alliance, Tibotec, Sanofi, Bayer, Sequella, and AstraZeneca gather at the CPTR Workshop to discuss new approaches to TB drug R&D. The collaboration was brokered under the Critical Path to TB Drug Regimens (CPTR), a cross-sector initiative designed to speed the introduction of shorter, safer, and more effective new TB drug regimens. The partners include AstraZeneca, Bayer, Sanofi, Tibotec, the TB Alliance, and the WHO. Combinations of drugs are required to treat TB to avoid the development of resistance. Since the launch of CPTR in March 2010, regimen development—testing and seeking the approval of combinations of new TB drugs as opposed to developing individual drugs, one at a time—is emerging as the gold standard within the field. Regimen development can telescope the time it takes to develop novel drug combinations, which show promise to shorten, simplify, and create safer and more affordable treatment. In the context of appropriate drug-sensitivity testing, novel regimens can treat both TB and MDR-TB, and truly transform the tools to fight the epidemic. CPTR and this agreement establish mechanisms for cross-sponsor information-sharing and begin to chart the course for cross-company collaborations on new TB drug regimens. Those who signed onto the agreement represent the majority of global sponsors with TB drugs in clinical development. Earlier this year, the combination of PA-824 (a novel chemical entity), moxifloxacin (an existing antibiotic not yet approved for treating TB), and pyrazinamide (an existing TB drug) completed a Phase II clinical trial. Meeting this milestones further confirmed both its potential as a regimen and the co-development approach to TB drug development. With this “proof of concept” trial completed, the door is now open to bring forward additional multi-drug combinations. Progress to develop novel drug regimens also requires advances in regulatory science to enable regulators to support and evaluate clinical trials that use this paradigm. This theme was echoed at the CPTR Workshop where this announcement was made, which featured a keynote address from the Director of the Center for Drug Evaluation and Research at the US Food and Drug Administration (FDA), Dr. Janet Woodcock. “I congratulate all of you coming together to solve what was previously perceived as an intractable problem,” said Dr. Woodcock. “Working together, we can take the steps needed to control this disease worldwide. We at the FDA, we will do everything we can do ensure that the regulatory process is not a barrier to getting this problem solved.” It is uplifting to see such a collaborative approach being to TB drug development adopted by its stakeholders, including the pharmaceutical industry. While harnessing the resources necessary to conduct future regimen trials remains a challenge, there is justifiable optimism surrounding the scope and pace of TB drug development, and in turn, the impact that the introduction of new and improved TB therapies can have on the health and prosperity of millions.

Jeff Meer is special advisor for global health policy and development at the Public Health Institute (PHI), a GHTC member. Based in Washington, DC, he provides strategic guidance to the organization on global health advocacy and develops new business proposals for global health projects. On Nov. 3-4, the Coalition Advancing Multipurpose Innovations (CAMI), a project of PHI, convened a symposium in Washington, DC, on “Multipurpose Prevention Technologies (MPTs) for Reproductive Health.” The gathering was attended by more than 100 product developers, researchers, academics, funding organizations, nongovernmental organization leaders, policymakers, and reproductive health practitioners. Participants discussed how best to advance emerging MPT science, with the goal of providing women around the world with safe, effective, low cost, and user-friendly means of protecting themselves simultaneously from HIV, other sexually transmitted and reproductive tract infections, and/or unintended pregnancy. The conference, funded primarily by the US Agency for International Development (USAID)’s Global Health Bureau and held at the Henry J. Kaiser Family Foundation’s Barbara Jordan Conference Center, follows a think tank convened earlier this year under the auspices of the Initiative for Multipurpose Prevention Technologies (IMPT), which is led by Bethany Young Holt of PHI. Other funders for the symposium include the National Institute of Health’s Office of AIDS Research, Gilead, and the Mary Wohlford Foundation. Dr. Young Holt directs CAMI, which serves as secretariat to the IMPT at PHI. Conference held to discuss Multipurpose Prevention Technologies (MPTs) and how they can help improve reproductive health to help women around the world . Photo Credit: Nguyen Ba Quang/PATH There are technologies already available to prevent unintended pregnancy and also block sexually transmitted infections. These include the male and female condom. However, newer MPTs are based on other technologies that may be more useable in some geographic and cultural contexts. These include impregnated vaginal rings, barrier devices, gels, and vaccines. The MPT field is developing a range of options for women, some of which may be more appropriate for different points in the life cycle. There are more than one dozen important MPTs now in development and testing, and some are much closer to commercial introduction than others. Among the topics covered at the symposium were: the state of the scientific field in developing MPTs; pressing issues like the effect of hormonal contraception on acquisition of HIV; the perspective of product developers; and regulatory pathways for MPTs in the United States and abroad. Other topics covered include: lessons learned from introduction of other reproductive health technologies; integrating end-user needs in product development; donor perspectives; public-private partnerships for MPT development; and political leadership on MPTs. Many experts consider MPTs to be a key global health technology area. Technologies such as MPTs that address multiple global health challenges—similar to vaccines that address more than one illness—can be both efficient and cost-effective interventions. And the twin challenges of preventing unintended pregnancy in order to reduce maternal mortality and reducing the transmission of HIV and AIDS are certainly high on the global agenda: they are the subject of United Nations Millennium Development Goals 5 and 6. Also, making inroads in these areas could offer substantial cost savings to governments and consumers alike. For example, in the United States alone, the estimated direct medical cost of unintended pregnancies in 2002 was $5 billion. Direct medical costs associated with treatment and care of sexually-transmitted infections in the United States in 2006 were even higher—approximately $14.6 billion. Despite this encouraging landscape, the MPT field is also fraught with challenges. Collaboration across scientific disciplines is never simple, and the worlds of research on contraception and sexually-transmitted infections do not necessarily regularly intersect. There are also significant regulatory hurdles to the introduction of technologies that deal with multiple health issues, and these can be daunting in trying to introduce even helpful and potentially life-saving technologies on a global scale. And any global health technology must pass the ultimate test of user acceptability. This symposium is meant to ask and answer some of these vexing questions, so that MPTs can be introduced successfully the first and every time. More information about the rationale for MPTs can be reviewed here.

Eleonora Jiménez–Levi is a senior researcher for the Treatment Action Group (TAG), a GHTC member, and wrote this blog post in conjunction with the release of a new report from TAG about funding for tuberculosis (TB) research and development (R&D). TAG has released a new report in collaboration with the Stop TB Partnership, which finds that in 2010 the world invested just $617 million in TB R&D—less than one-third of the estimated $2 billion annual investment needed to eliminate TB as a public health threat by the year 2050. The report, Tuberculosis Research and Development: 2011 Report on Tuberculosis Research Funding Trends, 2005-2010, tracks annual research spending across six TB R&D areas against funding targets set by the Global Plan to Stop TB 2011-2015. The report offers year-to-year data on the leading TB research funders and underscores the urgency of adequate and sustained funding. Dr. Lucica Ditiu, Executive Secretary of the Stop TB Partnership, emphasized this critical need for sufficient funding by saying “with current levels of funding it will be impossible to meet the research targets of the Global Plan to Stop TB 2011-2015. This is a completely unacceptable situation, because those targets are, I would dare to say, even modest. Where is the funding to push ahead research for a point-of-care diagnostic test accessible to all, new drugs for a shorter treatment time and a fully effective vaccine?” For the sixth consecutive year, R&D for TB treatment was the most well-funded research area—growing by 19% from $192 million to $227 million. However, this was just 31% of the $740 million annual Global Plan target for TB treatment research. The report also documents significant funding declines in basic science and vaccines research, which dropped 27% and 29%, to $126.6 million and $78 million, respectively. TB diagnostics accounted for 7% of global total spending with $44.6 million—a 15% increase from 2009. The infrastructure/unspecified category grew 46% to $83 million and operational research rose 17% to $58.1 million in 2010. Measuring these totals against the Global Plan targets, the only category to come close to its annual target was operational research and the farthest one was TB diagnostics. According to the World Health Organization, there were 8.8 million people newly diagnosed with TB and 1.45 million deaths in 2010, including 1.1 million new cases and .35 million deaths among people with HIV. Resources to develop new tools to prevent, detect, and treat TB have never been more urgent. “Recent progress in TB research is clearly threatened by stagnating funding,” said TAG’s executive director, Mark Harrington. “After several years of increasing investment, TB research is finally making headway with two new promising drugs for the treatment of multi-drug resistant TB and a new drug combination active against both drug sensitive and drug resistant TB. Cutting investments now will cost lives in the future.”

Claire Wingfield is a Product Development Policy Officer with PATH. This week, she’s blogging from the World Health Summit in Berlin, Germany. The third annual World Health Summit is currently underway in Berlin. The Summit brings together researchers, policymakers, funders, advocates, and health care providers to discuss global public health policy and research. This year’s theme is “Today’s Science – Tomorrow’s Agenda,” but the hot topic in almost every session that I have attended so far has been the need for innovative and sustainable funding mechanisms for global health in this time of financial uncertainty. Incentive prizes were highlighted as a mechanism for encouraging investment in research and development (R&D) of neglected and orphan diseases. These results-based rewards (as opposed to recognition awards like the Nobel Prize) “pull” innovation by encouraging applicants to submit ideas. The models and types of prizes vary. Some may offer millions of dollars while others provide the winner with access to laboratory services for future research. The first incentive prize, sponsored by the British Parliament in 1714, resulted in breakthroughs in navigation with the winner getting a whopping £100,000. The prize model often attracts new ideas and people to a field and is results focused which is attractive in an environment where funders want to see “quick wins.” Product development partnerships (PDPs) have also been highlighted at the summit as a successful model for accelerating R&D. Regina Rabinovitch of the Bill & Melinda Gates Foundation attributed the PDP model with feeding the largest research pipeline for neglected disease tools, increasing collaboration across the public and private sectors, and promoting a better understanding of the complexity of the product development process. While the successes are promising, she warned that as the number of products moving through the pipeline grows, so do the costs. Each phase of clinical studies requires more volunteers, more data points, more demands on the research site, longer trials, and increased regulatory complexity. Given these challenges in a constrained financial environment, PDPs and other research networks must increase collaboration and share costs by doing things like site sharing and harmonized training. They also need to focus their research efforts by prioritizing the products in the pipeline and weighing their potential public health impact. Bernard Pécoul, Executive Director of the Drugs for Neglected Diseases initiative (DNDi), stressed that it is critical for public sector partners to set objectives and priorities to ensure that product development is driven by health needs. Representatives from pharmaceutical companies—Novartis and Sanofi in the sessions that I attended—acknowledged that there are inherent difficulties with trying to reconcile limited profit potential with great public health need. There are many differing views on how to address this challenge with no clear consensus. One suggestion that seemed to be well received was that pharmaceutical companies can offer untapped areas of expertise, specifically in regulatory science, manufacturing, distribution, and pharmacovigilance. These are critical components of the R&D process, and many academic and public sector research institutions would benefit from training and mentoring in these areas. Recognizing that there is no magic bullet and that no one organizational or funding model can address the R&D needs for all neglected diseases, it is clear that limited resources must be leveraged, communication and coordination among research institutions across sectors needs to be increased, funding sources must be diversified, and current levels of support need to be sustained in order to maintain the recent momentum in global health research.