Building the Foundation for Developing Next-Gen Contraceptives
Access to safe and effective methods of family planning is fundamental to health, education, economic opportunities, and empowerment. Access, however, must mean more than having products present on shelves (although it has to mean that too). To achieve what might be coined as “transformational access,” a level of sustainable access that truly meets the needs of women, we need products that are easier to use, readily fit with women’s lives and preferences, and don’t create their own barriers to continued use.
Unfortunately, this is the challenge for millions of women globally who struggle with side effects associated with hormonal methods, particularly changes in menstrual bleeding patterns, which are strongly associated with method discontinuation. While these are among the most effective and safest pharmaceutical products that have ever been developed, they also present women with the regular decision to use a product that presents daily challenges in their life. For this reason, discovery of non-steroidal contraceptive drugs has long been something of a holy grail in contraceptive R&D.
Given the limited funding this space has seen historically, as well as the lack of pharmaceutical industry investment, the R&D ecosystem and available tools for early stage contraceptive drug discovery has remained unfortunately underdeveloped, despite ample opportunity to take advantage of developments in other areas of reproductive biology and new drug discovery approaches that were not available previously. Discovery of new contraceptive agents will remain elusive unless something changes to dramatically improve the state-of-the-art for contraceptive screening and pre-clinical testing, making this a field ripe for innovation.
One of the ways that the Bill & Melinda Gates Foundation funds high-risk, innovative research is through the Grand Challenges Explorations program, a unique program in which short grant applications undergo a champion-based review process focused solely on the merit of the core idea. (Read more about the Grand Challenges family of initiatives.) Through this program, we released a call for proposals in 2016 seeking projects that would bring advances in reproductive biology to bear on establishing tools for contraceptive discovery, as well as projects that would apply new drug discovery tools to the field of contraception.
In developing this, we were not interested in proposals for the development of specific contraceptive products; rather, projects had to propose development of broader approaches that could serve as the basis for a modern contraceptive drug discovery program. This decision is based on the belief that if we can establish a more robust toolset for contraceptive discovery, we can improve the probability of success for any given product development project. In other words (to borrow a saying from economics), “a rising tide lifts all boats.”
In the end, this call kick-started 13 projects that collectively represent a significant step forward in advancing non-hormonal contraceptive discovery, and which bring new concepts, approaches, and investigators to bear on some critical barriers to progress in this field.
So, what do these projects bring to the table that we can be excited about?
First and foremost, a number of these projects are looking at new ways to identify novel contraceptives, whether through the development of new biological assays for ovulation, follicle rupture, or sperm function or through the application of established model organisms where sophisticated and well-developed tools exist already, providing an opportunity to rapidly explore mechanism-of-action for active hits.
Second, application of new technologies to contraceptive R&D, as well as creative use of established tools in new ways, presents major opportunities to elevate the entire field. This can be exemplified by projects exploiting CRISPR-based gene editing, DNA-encoded compound libraries, lentiviral shRNA screening, and other tools. These technologies are accelerating progress in drug discovery for other areas, and there’s no reason to think the same can’t be true for contraceptives.
One of the major barriers to progress in the field of contraceptive discovery has been the biological complexity of critical reproductive processes and the fact that, in many cases, these have not been amenable to straightforward exploration in the laboratory. Work to address some of these technical gaps, for example by developing in vitro models of complex tissues or by establishing small animal models that may better mimic human reproductive processes, can provide opportunities to more deeply explore key mechanisms for contraception or understand likely side effects on reproductive tissues far earlier in the research process than would otherwise be possible.
While it’s encouraging to see new directions being explored in pursuit of non-hormonal contraceptive alternatives to current methods, there is clearly much more that could be done, and much more that will have to be done before we see real impact with new types of products. In many ways, this remains a nascent (and neglected) area of research, despite highly valuable investments by others, notably the U.S. National Institutes of Health, who have maintained programs in contraceptive development over many years. We’re optimistic that these types of investments in new approaches will help de-risk the field, entice others to invest, and provide much-needed momentum in an incredibly challenging area of R&D, and I’m looking forward to seeing progress as these projects mature over the next year.