A short three months ago I wrote a blog about R&D leads in treating Ebola virus disease (EVD) with vaccines and therapeutics included in the Ebola pipeline.  The piece was sceptical about what could be achieved in the pace of product development, clinical trials and commercialization solutions for the emergency in West Africa.

Three months later, like many others, I am amazed by the response time by industry and coordinated action of governments, funders and implementors in accelerating R&D across interventions. Over this time period, EVD has also arrived on shores outside of the African continent in Spain, UK, France, Norway, Germany and USA. What I had considered early and unproven leads in August have now progressed rapidly to provide non-human primate data, first-in-man data and parallel planning for phase III trials, at-scale production, policy directives to deploy and supply financing.

EVD Vaccines

The World Health Organization and partners announced on Oct 23, their earliest timeline yet, hopes of introducing a brand new EVD vaccine to the field at scale by Q1 2015. Two candidates are currently in Phase I trials (GSK ChAD3 and New Link rVSV) and as many as five more vaccine candidates may enter Phase I trials in January 2015. Depending on the Ph I results returning in December, one or both of the leading vaccine candidates will be scaled up to Phase III trials in West Africa in January 2015. The clinical trials are now being designed with care among expert stakeholder groups. It is proposed that the large cohort trials will start with 20,000 health workers in Liberia and potentially 8,000 more in Sierra Leone. The positive externalities would be that beneficial outcomes are proved, the highest-risk group of people would be the first to gain protection. At the high-level meeting on Ebola vaccines, industry manufacturers pledged to increase capacity for production so supply constraints in the worst-case outbreak scenario can be reduced.

EVD Drugs

WHO technical consensus on whole blood therapies and convalescent blood serums are a priority for suffering patients. However, due to limited supply of blood, infrastructure for blood screening, processing and administration from surviving EVD patients and difficulty in logistics, this currently cannot be deployed as a wide-scale solution. There is support for the clinical trials of small molecule drugs (antivirals) that can be quickly and affordably produced without manufacturing constraints. In addition, the RNA and monoclonal Ab approaches will also commence efficacy trials, but face additional implementation hurdles such as complex manufacturing and high cost of goods to produce, thus resulting in constrained supply.

EVD Diagnostics

Diagnosing EVD in a person infected for only a few days is difficult, because the early symptoms, such as fever, are nonspecific to the disease and could be another infectious disease (malaria, typhoid, lassa fever, etc.). The US CDC recommends ELISA testing, PCR and virus isolation to identify EVD patients from other diseases. However, these tests currently require laboratory work and diagnosis and cannot be deployed at first-screening point of care.

The WHO is working with the Foundation for Innovative New Diagnostics (FIND), a public-private product development partnership, to check technical feasibility and closest match to target product profile for an EVD diagnostic to be developed. Multiple molecular and antigen detection technologies are being tracked by the diagnostics consortium with the following plan for commercialization:

Q1 2015: Validation phase

Q2 2015: Field trials conducted

It is important to concurrently accelerate the diagnostics work with high sensitivity and specificity to EVD at the same time as vaccine development. One of the common side effects of vaccines is the slight fever post-immunization and the initiation of the host immune response in reaction to the attenuated virus. Diagnostics will help distinguish if the fever is a normal side effect or presence of EVD itself.

Continuous Tracking the Call to Action

As the EVD outbreak continues to drain health resources in West Africa, other health indicators in the region are falling – for example, with the general population being too scared to visit hospitals, expectant mothers, patients with malaria, lassa fever and other health issues are not being appropriately treated. As the health indicators fall and business climate is hampered, West African countries start the spiral of downward economic impact, which is felt across the continent.

The R&D efforts have been accelerated by the global community, but the on-the-ground management of containment and control goes on day by day. Some may say the global community should have had these antidotes prepared since EVD was identified in 1976, others will see the accelerated development speed as a sign of further global collaboration. What lessons does this teach us about controlling other infectious diseases? That investments in basic research is important and that we cannot start from ground zero in outbreak situations? That, if there is political will, R&D for diseases of the poor can be accelerated across all areas? Perhaps in a World Bank proposed Emergency Fund? Overall, investments in health systems need to be higher on the global health agenda, since countries are better protected against any emerging threat if they have a strong defence.

Many questions, and answers are probably all of the above.

Julia Fan Li

Welcome to the Polar Continental Shelf Program

This post isn’t so much about biotech or even health as it is research overall, but stick with me, as I introduce a research base very few ever think of…

There have been recent highlights of the importance of the changes in the Arctic, monitoring of climate change, discovery of natural resources, territorial disputes over tiny islands and the tensions of economic development and environmental stewardship.

Daily transactions, policy briefs and international cooperation agreements are discussed, negotiated and approved with the help of essential research that builds the evidence for key decisions.  Where do the data come from? Who collects them? What organizations help enable research to be conducted in extreme conditions of isolation, cold weather and remote infrastructure?

I had the opportunity to find out during my inaugural visit to Resolute Bay in Nunavut, Canada, on the tip of the mythical Northwest Passage – home of the Polar Continental Shelf Program. The PCSP is located in the high-Arctic and coordinates field logistics in support of advancing scientific knowledge. It operates adjacent to the Inuit village of Resolute Bay. The PCSP was established in 1958 by the government of Canada and has built up a logistics support network that stretches approximately 2,160 km from Alaska to Greenland, and from the Arctic Circle to the geographic North Pole.  The PCSP also serves a secondary purpose as an Arctic base to support management of Canada’s lands and natural resources and contributes to the exercise of Canadian arctic sovereignty.

Arriving at Resolute Bay from the majestic Canadian ice-breaker the Louis S. St. Laurent (LSSL) via helicopter (as there is no port), it took several minutes for the reality of being in the Arctic Circle to sink in. The landscape was flat and barren, unlike the lush green forests and Rocky Mountains of the Canadian ‘south’.  The first room of the PCSP looks like a replica of an elementary school’s cloak room, with pegs and benches for personnel to de-layer from their coats, gloves, hats and other winter gear. Past two additional sets of doors, one enters the warm and welcoming 100-person cafeteria room, where copies of Nature can be found on the information table, next to Polar Bear warning brochures (yes, even the scientific journals make it to the land of the polar bears).

Each year, PCSP is the landing base/home for 1000+ scientists who conduct more than 165 research projects at more than 60 field camps across the Canadian Arctic.  Researchers rely on PCSP for equipment, logistics and knowledge of safety and cultural aspects of working in the extreme environment. PCSP arranges air and overland transportation, radio communications and navigation and global positioning.  It is able to coordinate and arrange research camps to share in logistics synergies and mitigate the risks and dangers of working in isolation in the high arctic. PCSP delivers about $10 million worth of logistical services to science projects ranging from anthropology to zoology. The transportation costs are immense and the terrain treacherous – the costs of disarray are high. PCSP acts as an Arctic liaison between Canadian Arctic residents and the incoming scientists, providing advice on permitting, licensing and environmental assessment process that makes the science possible. In practical terms, PCSP also provides accommodation, daily catering, internet and working space. Specialty laboratory extensions include a walk-in freezer, fume hoods, compressed-air supply and a water purification system. There may not be rows upon rows of drug development or green biotech happening in the Arctic, but the one can feel the air of insatiable curiosity to know more about the edges of our world.

Resolute is one of the globe’s coldest inhabited places, with an average yearly temperature of -16.4˚C. My visit to PCSP came at the close of the 2013 ‘summer’ research season, as the Resolute Bay base had ushered all the scientists home and completed Operation Nanook for the Canadian military. We were the last large visiting party for the lean staff of PCSP to manage. Tim McCagherty and Glen Parsons were the PSCP managers on duty and shared with us the important work of the base. Even at the end of the 2013 season, the two men talked with energy, enthusiasm and gusto about the need to understand the North and to achieve that understanding with respect and safety.

The PCSP team welcomed the 2010 Canadian government investment of $11 million to refurbish the PCSP, doubling the number of beds available and adding leisure areas and an exercise room. The staff reminded us that for scientists engaged in short intense periods of research, it is important they have a comfortable start and end to their projects. Conducting frontier research in Canada’s remote Arctic is not without its dangers – the nexus community has suffered losses in 2011 with the crash of a Boeing 737 and recently in September 2013 with the loss of a Canadian coast guard helicopter.

I came away from PCSP with a new appreciation of frontier research. With the development issues of the Arctic coming to the fore with climate change, it is important to know where our research comes from and the support network that it takes to obtain data and evidence.  Government investment in basic science is not only about the principle investigators, but also the community of hard-working personnel who support frontier research.

Julia Fan Li

Source: They Go to Die

Over the past one year, I have completed a series of blog posts on this platform relating to tuberculosis – a (mostly) curable infectious disease that still claims approximately 1.8 million lives per annum.  The articles have focused on how ‘push’ and ‘pull’ incentives can accelerate research and development for new TB vaccines, TB drugs, TB diagnostics and improved TB care delivery methods to those living at the lowest rungs of the global economic ladder.  A conference was hosted to bring together strands of innovation, access and investment from across disciplines to overcome financial, political and systemic barriers of fighting tuberculosis effectively.

But there is one area where articles and conferences sometimes fail – at storytelling.  Researchers are often encouraged to share their findings through publications and data, but as good as aggregate data are at providing resounding proof, they also bury the underlying human stories and emotions that connect us all.  On September 14, 2011, in the midst of my TB innovation research at Cambridge University, I came across a twitter message that asked me to check out a trailer for a small documentary.  The trailer for the film, “They Go to Die” was hosted on Kickstarter – a crowdsourcing funding platform for creative projects.  I was intrigued.  For 4 minutes and 42 seconds, I sat transfixed to my computer screen; the trailer blew me away. Another TB researcher across the Atlantic at Yale University had taken a video camera and followed the lives of 4 miners affected with TB back home from the mines of South Africa.  The researcher needed $13,000 to finish his documentary.  I gladly contributed to my first crowd-source funding project that day.

Approximately 18 months later, on March 22, I sat in the auditorium of the London School of Hygiene and Tropical Medicine and watched along with 120 others, the London screening of They Go to Die.  The screening was hosted by RESULTS UK and Medsin UK and included an update by the filmmaker/epidemiologist behind the project, Jonathan Smith, on the events that have occurred since he first started the project.  Out of the four men featured in the documentary, only one, Mr. Mkoko remains alive today. Mr. and Mrs Mkoko addressed the International AIDS Conference last year on the power of the family unit in combating tuberculosis (Mr Mkoko’s children often gave him hourly reminders about his regimented pill-taking to fight HIV and MDR-TB co-infection).  Also last year, building on over a century’s worth of research into tuberculosis in the mining industry, a “Declaration on TB in the Mining Industry” was signed by 15 Heads of State from southern African countries.

What is research if research doesn’t help drive positive change? That’s the message that lingers with me from the documentary.  When we work in our worlds of drug discovery and development, we are very much upstream from the end patients we aim to help. A waterfall of decisions are made on clinical data points – some decisions affecting R&D programs, some affecting national policies and some in the way sectors operate. Perhaps sometimes we need creative mediums such as film to tell the stories of our data collected and to keep driving toward positive change for those that can be helped by our research, our actions and our united voices.

Julia Fan Li