A number of pre-existing medicines already approved for treating non-Ebola diseases were considered early in the epidemic response for re-purposing to treat Ebola because they had demonstrated efficacy against the virus in in vitro. The advantage of considering re-purposing of drugs is that these were readily available, and their safety was known.
A clinical trial of the drug favipiravir (Toyama, Japan), started in Guinea in late 2014 under the auspices of INSERM, MSF and the Guinean government. Initial results suggested that the product might have some activity against the virus in the early stages of infection and this warranted further research. One other re-purposed drug, interferons, has been assessed in Phase II trial in Guinea. Due to risks of symptom exacerbation, enrollment was limited to patients with recent symptom onset.
Other products specifically developed for Ebola are still in development, including the monoclonal antibody cocktail ZMapp (Leafbio, USA) and monoclonal antibody cocktail MIL 77 (MabWorks, China). ZMapp was tested in small Phase I clinical trials in the UK and US and is currently being tested in Sierra Leone. MIL 77 is prescribed to Ebola patients under compassionate use. An investigational New Drug (IND) application for a Phase I trial of this drug was filed in China.
The scientific community is also testing in non-human primates a wide range of other drugs that have been proposed as potential therapies and will be taking the most promising into early phase clinical trials.
Blood and blood products
Convalescent whole blood donated by Ebola recovered patients has been administered in Sierra Leone in a trial run by the government since late 2014. The trial is currently not enrolling. A trial of convalescent plasma began in Liberia at the same time – under the auspices of ClinicalRM (a clinical research organization) with the US government and the Bill and Melinda Gates Foundation, but was discontinued due to lack of Ebola cases. Guinea is currently running a plasma trial through a partnership with institutes in Belgium, the UK, France and MSF.
Phase II/III trials of convalescent whole blood are currently on hold in Sierra Leone to accommodate a Phase II/III convalescent plasma trial. So far, about 150 patients have been transfused in Sierra Leone and Guinea.
Data from these trials are currently being analysed for evidence of efficacy and standards are being developed.