As Coronavirus continues to spread across the globe, Rachel Howard explores what pharma is doing to advance research into the virus, considering lessons learned from previous public health emergencies of international concern.
Biologics are big business in Rheumatoid Arthritis (RA), with the first wave of TNF inhibitors Remicade (infliximab), Enbrel (etanercept) and Humira (adalimumab) all having achieved blockbuster sales since their launches in the early 2000s.
Over the last month, our newsfeeds have increasingly been dominated by updates on the novel coronavirus (COVID-19) outbreak. Believed to have originated in a live animal market in the Chinese city of Wuhan, at the time of publishing COVID-19 has registered over 75,000 confirmed cases and 2000 deaths, with 29 countries and territories affected. nCoV is in the same family as SARS (Severe Acute Respiratory Syndrome), another strain of coronavirus identified in 2003. While nCoV looks likely to have a lower fatality rate, it has spread much more quickly, with the number of reported cases already having rapidly overtaken SARS and continuing to grow by the day. All indications suggest the virus is highly contagious – including, critically, at the stage before an individual displays any symptoms of infection.
This outbreak was declared as a public health emergency of international concern (PHEIC) by the World Health Organization (WHO) on 30th January 2020, making it the sixth such emergency since the International Health Regulations came into force in 2005:
Declaring an outbreak as a PHEIC, in addition to placing immediate recommendations on response and containment, is a way of stressing the urgent need for the international co-ordination of research and development (R&D) efforts. This includes active participation in increasing knowledge of the virus and disease and advancing research – including in the important area of therapeutics and vaccines. This article explores what pharma is doing to lead that charge, considering lessons learned from previous PHEICs, each of which exposed new inadequacies in global epidemic preparedness.
Lessons from Ebola: off to a slow start
A Canadian laboratory had been working on an Ebola vaccine (rVSV-ZEBOV) for years, but with no real drive for development until the spiralling West African outbreak in 2014 generated urgent calls for containment. The lab offered to donate the still experimental vaccine, but it became clear a partnering pharmaceutical company with more experience was needed to support the vaccine’s development, which is how Merck got involved. A clinical trial program was rapidly initiated, and despite the extreme logistical challenges of implementation, the speed at which the trials progressed was unprecedented.
Fast-forward a few years to the 2018 outbreak in the Democratic Republic of the Congo, where Merck’s Ebola vaccine was offered under a compassionate use protocol. In late 2019, the vaccine, now called Ervebo, was granted EMA and FDA approval. Getting Ervebo to market has been widely hailed as a phenomenal achievement on the part of all organisations involved, given the criticism pharmaceutical companies have traditionally come under for neglecting infectious diseases in low-income regions due to lack of incentives from global market forces alone.
Merck has not been alone among pharma giants contributing to the fight against Ebola: J&J also has an Ebola vaccine candidate in its pipeline, and a number of investigational therapeutics were offered in the latest outbreak. Results from a multi-drug trial in which two of four candidates (Regeneron’s REGN-EB3 and the US National Institute of Allergy and Infectious Diseases’ mAb114) showed particular promise (with a 90% survival rate among those who received either drug shortly after infection), suggest further progress in the control of this disease, previously recorded as having mortality rates of up to 90%.
Lessons from Zika: the challenge of sustaining momentum
Zika virus, a mosquito-transmitted disease first identified in 1947, hit the headlines hard in early 2015, when Brazil reported a large outbreak of rash illness, and later an association with microcephaly. As outbreaks and evidence of transmission started to be reported in other countries and regions, pressure mounted to put countermeasures in place.
The race to find effective diagnostics and vaccines got underway more swiftly this time. The Biomedical Advanced Research and Development Authority (BARDA), an office of the US Department of Health & Human Services, was a key player in forming public-private partnerships to incentivise development. BARDA funding was directed toward a number of industry partners, such as a contract with InBios to develop a diagnostic test, cleared by the FDA in June 2019, and a contract with Takeda to develop a vaccine, which entered phase 1 clinical trials in November 2017 and received FDA Fast Track designation in January 2018.
However, the development of an effective Zika vaccine has been more challenging than first expected – Sanofi Pasteur had also been developing a Zika vaccine but dropped out of the process in 2017 when scientists found it was taking longer than predicted.
An inherent challenge of drug development in response to epidemics such as Zika is maintaining the urgency when outbreaks subside and collapse. The immediate need (and potential for profit) is no longer there once the threat wanes and coverage of the outbreak fades from the public eye. Investors in particular are quick to lose interest. Nevertheless, public health experts emphasise the necessity of continued development to protect against future outbreaks, and stress that vaccines are still required. Ensuring alignment of incentives across stakeholders throughout the development process is critical to maintain progress.
The response to nCoV (so far): speed is of the essence
The first difference from the prior outbreaks mentioned above is the sheer speed at which the nCoV story has progressed. With the virus originating in a densely populated area and major transportation hub, unlike Ebola and Zika it has taken weeks, rather than months, to identify and characterise, despite the fact that its strain has never been seen before.
The positives – effective leveraging of artificial intelligence (AI) to track transmissions and predict potential new cases, plus a commitment to open sharing of information across the global health community – have been marred by widespread “fake news”, misinformation, lack of transparency and reports of xenophobia, as borders are locked down and quarantines are imposed.
However, on a scientific front, early signs suggest that the life sciences industry and the global health community are better prepared than ever to accelerate development of new therapeutics and vaccines. This is the first major test for the Coalition for Epidemic Preparedness Innovations (CEPI), a public-private coalition that was set up in 2017 with the aim of “derailing epidemics by speeding up the development of vaccines”. CEPI has already initiated three programs to develop vaccines against this new strain, partnering with biotechs Inovio and Moderna, as well as the University of Queensland, with technological support from GSK. J&J is also working on a vaccine, as are a number of other biotechs, domestic Chinese pharma companies and academic organisations.
However, as with the Ebola and Zika outbreaks, whether any of these vaccine candidates will be deployed in time to make a difference and successfully curtail the devastation of this outbreak is another question. Even with the accelerated development timeline, J&J do not expect their vaccine to be ready for testing in humans for at least eight months, which may already be too late.
The other pharmaceutical front of defence is therapeutics, and again major pharma companies have been quick to step forward and throw their hats into the ring; Gilead is currently working with Chinese health authorities to test their experimental antiviral drug remidesivir, while AbbVie reports promising results from a mixture of its HIV medication Kaletra in combination with Roche / Chugai’s Tamiflu.
The markets have reacted and biotech stocks are surging on these announcements, but at this stage it is hard to predict how this will play out. Will nCoV be a flash in the pan that fizzles out fairly quickly, like MERS (Middle East Respiratory Syndrome), another coronavirus that caused concern in 2014 but never reached PHEIC stage, or will it become a catastrophic pandemic (an epidemic of global proportions)?
Cynical commentators suggest that pharma has been more ready to get involved in developing vaccines and therapeutics for nCoV because it poses a more direct threat to mature markets with economies who can afford to pay for prevention and treatment. They also argue that those of us outside of China would be better off worrying about the flu, which continues to kill hundreds of thousands every year despite the widespread availability of influenza vaccines. But others see alarming warning signs, pointing to nCoV’s highly transmissible nature and the soaring caseloads to date.
For now, only one thing is for sure – a multi-disciplinary response, involving close collaboration between both public and private stakeholders, and taking heed of the challenges encountered in previous epidemics, will be essential to maximise our chances of tackling the virus successfully.
Research Partnership has specific experience conducting strategic engagements for companies developing global health vaccines and therapeutics in response to infectious disease outbreaks.