EBO-PEP 2026

The challenge

Before they are diagnosed and isolated, patients with Bundibugyo virus (BDBV) infections are likely to come into contact with various healthcare workers, household members, and others. These individuals may have been exposed to BDBV and are therefore at increased risk of BDBV infection and disease. 

Post-exposure prophylaxis (PEP) can protect these individuals. During the virus’s incubation period, which can last up to three weeks, antivirals, monoclonal antibodies and/or vaccines could be given to boost host defences and prevent the virus from gaining a foothold. PEP has been shown to be highly effective at preventing HIV and other viral infections, and was deployed during earlier Zaire ebolavirus outbreaks, when no cases occurred in PEP-treated individuals.

Options for PEP are limited for BDBV, but some evidence suggests that direct-acting broad-spectrum antivirals may inhibit the virus.

The project

The EBO-PEP 2026 project is organising a randomised controlled trial to assess the potential benefits of obeldesivir-based post-exposure prophylaxis for close contacts of BVBD patients. Obeldesivir, a derivative of remdesivir, is a promising option for PEP, as it has shown good activity in preclinical studies. Unlike remdesivir, it is an oral drug, making it easier to deliver in challenging outbreak contexts.

The BDBV-focused project builds on the existing Global Health EDCTP3-funded EBO-PEP project, which aims to evaluate PEP for other forms of Ebola infection. It was mobilised to launch research during a Zaire ebolavirus outbreak in the DRC in late 2025, but the outbreak was contained so quickly that no data could be collected. However, the infrastructure, partnerships and community engagement developed for this outbreak have facilitated a rapid pivot to a BDBV research project.

The main BDBV trial will take place in the DRC and be integrated within the national disease control response, with close collaboration with the Ministry of Health and humanitarian actors. Almost 1,000 close contacts of BDBV patients will be randomised to receive either obeldesivir or a placebo, administered daily for 10 days under direct observation. Participants will be monitored for signs of infection and regularly tested for BDBV infection. 

Children are at high risk of severe disease, with mortality rates higher than 80% seen in previous Ebola outbreaks. Pregnant women are also at particular risk of severe disease and adverse pregnancy outcomes. A placebo-controlled trial is not considered ethical in these groups. Instead, they will be recruited into a complementary cohort study and provided with remdesivir as PEP. This will provide data on the safety, effectiveness, and feasibility of PEP in these groups, as well as information on the natural history of infection and host responses. 

EBO-PEP 2026 is one of four projects funded through an emergency call for proposals launched in response to the Bundibugyo Ebola outbreak in the Democratic Republic of the Congo (DRC) and Uganda in 2026.

Impact

The EBO-PEP 2026 project will generate vital data on the potential benefits of BDBV PEP. It will:

• Show whether obeldesivir can prevent infection or reduce the severity of symptoms when given to close contacts of BDBV patients.
• Reveal whether PEP is acceptable and can feasibly be delivered in outbreak contexts.
• Provide data on the costs and cost-effectiveness of obeldesivir-based PEP.

If shown to be effective, obeldesivir and remdesivir are readily available therapeutics that could be rapidly deployed in PEP programmes to reduce the risk of severe disease in groups at high risk of acquiring BDBV infections.