In March 2014 the first official cases of Ebola were reported in Guinea and Liberia. Nine months on, the outbreak has escalated to the most severe in the disease’s history, claiming over 6000 deaths. Until 2014, there were just over 1000 recorded cases in forty years. It is therefore hardly surprising Ebola was off the drug industry’s radar. The current crisis in West Africa has highlighted the challenge of developing new pharmaceuticals for neglected tropical diseases.
The first known outbreak of Ebola occurred in Zaire (Democratic Republic of Congo) in 1976. Ebola causes flu-like symptoms, followed by haemorrhagic fever and multiple organ failure. Spread by contact with an infected person’s bodily fluids, health workers are particularly exposed to infection – a problem made worse as the countries affected have some of the lowest supply of doctors per 100,000 population. With the number of cases doubling rapidly, and in the absence of proven vaccines or antiviral therapies, treatment has focussed on outbreak control measures – surveillance, quarantine, safe burials, and public health education. Mortality rates in previous outbreaks were between 80 and 90%; today, with better sanitation, mortality in the current outbreak is estimated at around 40%.
The unprecedented spread of Ebola across West Africa has been exacerbated by a lack of treatments or vaccines. Drug development is a slow, expensive, bureaucratic process, often taking up to 15 years for an initial breakthrough to culminate in a product approved for human use. Huge financial investment is needed in the search for new drugs or vaccines – and most attempts do not succeed. When a product breaks through to market, it is priced to recover the losses of previous failed attempts. The ‘ideal’ drug for a pharmaceutical company to produce will regularly treat a large number of people in rich countries, where individuals have strong purchasing power or substantial health insurance. Ebola outbreaks occur intermittently, affecting a relatively small number of people in some of the world’s poorest countries. There is a lack of incentive for pharmaceutical companies to invest in products exclusively used by countries which lack the ability to pay for them. As a consequence, only 1% of the treatments developed between 1975 and 1999 were for tropical diseases.
Ebola affects the bottom billion – poor people in poor regions. Guinea spent $32 per person on healthcare in 2012, compared with $3,647 per person in the UK or $8,895 per person in USA. It is clear that without international aid, the affected nations could never afford the vaccines, should they become available. NGOs providing frontline medical assistance, such as Médecins Sans Frontières, Red Cross, and UNICEF, have seen a large surge in donations. Governments have also stepped up: USA has contributed more than $450 million to the UN’s main Ebola relief fund, and the European Commission is contributing €140M to Ebola research, matching funds from drug companies. Calls for a contingency fund to prevent other outbreaks, and long-term funding to improve health systems have been welcomed, however whether the financial commitment from governments will endure past this current outbreak remains to be seen.
Ebola vaccines are unlikely to ever make a large profit. Instead, drug companies act on political pressure and moral incentives – the social value of curtailing the epidemic is much larger than the private value of selling the vaccine. As a public awareness of the humanitarian problem grows, each pharmaceutical company is responsive to the positive publicity they could gain if their vaccine succeeds. Their reputations are also at stake, if vaccines are rushed into production which later prove to be ineffective or lead to serious adverse events.
Although initially slow to respond to the crisis, in August 2014 World Health Organisation (WHO) ordered an unprecedented acceleration of normal drug development processes. Three front runners have emerged. GSK’s vaccine is based on a chimpanzee cold virus called ChAd3. Their Phase I trial in US has reported positive preliminary results, with further trials ongoing in UK, Mali and Switzerland. Stage II and III trials will run concurrently in early 2015. Johnston and Johnston are also developing a vaccine, and Merck is a late entrant to the market, having recently acquired the licence for experimental Ebola vaccine created by smaller bio-tech firm NewLink. The companies have shown willingness to work together to find the best combination of treatments, whilst regulators are drawing up guidelines on how much data they require to approve vaccines at this accelerated speed, without compromising safety, scientific rigour or ethics. Vaccines are expected to cost around $100 per dose, funded by government agencies and NGOs.
Whether an effective Ebola vaccine is developed or not, this will almost certainly not be the last outbreak of a neglected tropical disease. Cheaper air travel means outbreaks which once remained localised can now spread across the global very quickly. Had a vaccine been available before the first few cases, the outbreak could have easily been curtailed. If or when an effective vaccine for Ebola is developed, it will likely be stockpiled in preparation for future outbreaks. But the real test is with the drug development process itself: can pharmaceutical companies and regulators work together to produce a safe, effective vaccine with record speed and efficiency? Can international aid organisations and governments develop a new finance mechanism which will better protect some of the world’s poorest people from the next infectious disease crisis? And will the current media spotlight on this humanitarian crisis mean other tropical diseases will be neglected no longer?