Ebola virus overview
Ebola is a viral haemorrhagic fever caused by ebolaviruses., Ebola virus is a member of the Filovirdae family of viruses and was first identified in 1976 in the Democratic Republic of the Congo (DRC).
Several outbreaks have since been reported from Central and Western Africa with the largest occurring in March 2014.
The disease primarily spreads through direct contact with body fluids such as sweat, blood, faeces, vomit, saliva, genital secretions and breast milk of infected patients. It is also transmitted through the use of non-sterile injections.
There is no evidence for airborne transmission of the disease in humans.
Symptoms of Ebola
The common symptoms of Ebola are fever, fatigue, sore throat and severe headache. It also causes nausea, diarrhoea, rash and in some cases internal and external bleeding.
The incubation period ranges from two to 21 days and human transmission is possible after an infected person develops symptoms.
Ebola virus outbreak: 2014-2016
A potential outbreak was first noticed in Guinea in February 2014 and it spread rapidly to neighbouring countries. The outbreak was declared an international public health emergency by the United Nations (UN) in August that year.
Control and containment measures
The public health authorities and governmental agencies took an array of steps to restrict the spread of the disease during the 2014-2016 Ebola outbreak. It included rapid isolation, setting up Ebola Treatment Units (ETUs) for treating patients and screening efforts to identify people exposed to the disease.
The Island clinic in Liberian capital Monrovia offered treatment to 120 patients during the first phase, while additional centres were subsequently built to increase the capacity.
The government also took initiatives to hire new personnel and train teams for burials. Several campaigns were started to deliver Ebola-related messages via television and radio.
The authorities focused on increasing capacities and contact tracing to identify hotspots and identify new cases in the second phase. Steps were also taken to strengthen community engagement to educate communities on the disease.
The primary objective during the third phase was to break the disease chain as well as address the consequences of residual Ebola risks.
The outbreak was contained by mid-2015 by implementing aggressive isolation measures and border controls. More than 28,000 infections were confirmed in the epidemic with Guinea, Liberia and Sierra Leone reporting the maximum number of cases.
A total of 11,323 people died during the outbreak. Liberia confirmed 4,809 fatalities, the most by any country. The Liberian Government ordered the cremation of all those who died of Ebola to minimise transmission risks.
Ebola virus outbreak: 2018–Present
The DRC reported a new Ebola outbreak in the province of North Kivu in 2018. The outbreak reported 3,457 cases and 2,277 fatalities by 14 April 2020.
Control and containment measures
The lessons learnt from previous outbreaks helped during the 2018 epidemic. DRC used the Ebola treatment centres to provide treatment to the patients. Some confirmed cases were enrolled into compassionate use programme.
The 2018 outbreak also saw increased use of community engagement and contact tracing activities in addition to screening at all major transportation points of entry.
Further, the World Health Organization (WHO) and the DRC started using recombinant Vesicular Stomatitis Virus–Zaire Ebola virus (rVSV-ZEBOV) as an investigational vaccine to control the outbreak.
Ebola versus COVID-19: Disease and outbreak comparison
A study of the Ebola and COVID-19 diseases indicate that the latter is more easily communicable but involves a lesser risk of death.
The first case was reported from a village in Guinea in December 2013 during the 2014 outbreak. The officials were notified in January 2014 and two months later the outbreak was declared an epidemic.
The outbreak reached Liberia and Sierra Leonne in July that year, prompting the WHO to declare a Public Health Emergency of International Concern (PHEIC) a month later.
The WHO lifted the PHEIC status in March 2016.
Ebola’s mortality rate stood at around 40%. Majority of Ebola cases were identified in Western Africa, with at least two outbreaks reaching epidemic proportions.
The first case of atypical pneumonia was reported by Chinese state media on 31 December 2019. The virus was named SARS-CoV-2 and the disease was named COVID-19 on 11 February 2020.
The WHO declared COVID-19 as a pandemic on 11 March 2020.
The mortality rate for COVID-19 is around 1%-3%. The outbreak reached pandemic levels in three months and affected 185 countries.
Pharmaceutical industry response to Ebola
More than 80 vaccine candidates entered developmental phase since the beginning of the Ebola outbreak. The developers included Moderna, GlaxoSmithKline (GSK) and Merck. A majority of the candidates, however, did not enter the clinical phase.
Merck subsequently developed an efficacious vaccine for Ebola, which has received approval in multiple regions.
Merck’s Ervebo was the first Ebola vaccine to secure approval in the US and European Union (EU). The live-attenuated, recombinant viral vaccine was approved for use to prevent the disease caused by Zaire Ebolavirus in individuals 18 years of age and older in 2019.
The duration of protection provided by the vaccine is not known and it is not effective against other species of Ebola virus.
Johnson & Johnson’s Ad26.ZEBOV (VAC-52150) is approved in the EU. The candidate is a combination of two viral-vector vaccines.
Ad5-EBOV is a recombinant defective human adenovirus type 5 vector-based vaccine developed by CanSino Biologics. It was approved in China in 2017.
GSK developed the cAd3-EBO vaccine, which entered Phase II testing in 2015. It is based on a non-replicative Chimpanzee adenovirus expressing glycoprotein of the Ebola Zaire strain (ChAd3-EBO-Z). The license for the vaccine was transferred to the Sabin Vaccine Institute in 2019, which is evaluating the vaccine in a number of clinical trials.
The enthusiasm towards developing therapies for Ebola was strong initially with more than 200 therapies being developed. These included small molecules, therapeutic antibodies and combination of antibody treatments.
REGN-EB3 developed by Regeneron Pharmaceuticals is a fixed-dose combination of the three monoclonal antibodies atoltivimab, maftivimab, and odesivimab against the Zaire Ebola virus glycoprotein. It was approved by the US Food and Drug Administration (FDA) in October 2020.
mAb114 (ansuvimab) targets the receptor binding domain of Ebola virus glycoprotein. It was developed by Ridgeback Biotherapeutics in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center.
The therapeutic is a monoclonal antibody that was obtained from a human survivor of the 1995 Ebola outbreak in the Democratic Republic of Congo. It was approved by the FDA in December 2020.
Gilead Sciences’ remdesivir is a nucleotide analogue, which targets viral polymerases but its development for Ebola has been discontinued.
Mapp Biopharmaceutical’s ZMapp is a fixed-dose combination of the three monoclonal antibodies cosfroviximab, larcaviximab, and porgaviximab. It entered Phase III trials, but it was found to be less efficacious.
Future of Ebola virus management and considerations for pharmaceutical development
The Ebola virus outbreaks have been sporadic despite its severity. There are also very few patients requiring Ebola treatment, accordingly enrolments in clinical trials dried up.
The financial opportunities remain low as the disease is not considered a public threat at the moment. Routine and widespread Ebola vaccination programmes are also unlikely, as the disease incidence remains low.
Further, the cost savings associated with routine inoculations will be low, due to intermittent outbreaks. Any future development must be driven by governmental or academic institutions due to low interest.
Lessons learned and implications for COVID-19
Rapid Response Ability
The development of prophylactic and therapeutic interventions started soon after the Ebola outbreak. It demonstrated the pharmaceutical and drug development industry’s ability to respond to such health crises.
The momentum weakened after the outbreaks were contained and due to difficulties in finding enough participants in clinical trials. It also highlighted that the industry should not lose enthusiasm until effective agents are found.
A similar and a more robust response was seen during the COVID-19 pandemic. Hundreds of agents entered developmental phase within two months of the virus’ discovery.
The drug development industry adopted drug repurposing strategy in a bid to expedite time to market of the agents during the Ebola outbreak. It involved marketed or in pipeline drugs being tested for treating Ebola. Some examples of such drugs are brincidofovir and imatinib. Brincidofovir was originally being developed for multiple viral infections, while the latter was approved as a treatment for several types of cancer.
Similar strategies were adopted during the COVID-19 pandemic. One such drug, remdesivir, which was once investigated for treating Ebola, was widely used to treat COVID-19 across several countries.
Antibodies as therapies
One of the most promising therapies for Ebola was a combination of three antibodies underlining the potentiality of such therapies for treating infectious diseases.
Antibodies obtained from COVID-19 recovered patients were used to fuel the development of therapeutics during the coronavirus pandemic.
Focus on profitability
More than 200 vaccine and therapeutic agents entered development for Ebola. The development, however, stagnated due to difficulties in running clinical trials among other reasons. The sporadic incidence rate and the presence of an approved vaccine further diminished the prospects of subsequent development.
The COVID-19 therapeutic development programmes will not face the same challenges, as the pandemic continues to ravage the world. The developers are also expected to leverage the financial opportunities, given that the world may require necessary interventions for several years.
The interest, however, is likely to decline when a number of safe and effective vaccines and therapeutics reach the market.