WHO recommends two mAbs in fight against Ebola

By Rachel Arthur

- Last updated on GMT


Related tags Ebola Monoclonal antibodies WHO World health organization

The World Health Organization (WHO) has published its first guidelines for Ebola virus disease therapeutics, issuing ‘strong recommendations’ for the use of two monoclonal antibodies.

The two monoclonal antibody treatments, mAb114 (Ansuvimab; Ebanga) and REGN-EB3 (Inmazeb), were selected by the WHO following systematic review and meta-analysis of randomized clinical trials, with the organization highlighting ‘clear benefits’ from the therapeutics.

In 2019, Inmazeb became the first ebola virus treatment approved by the FDA. Ansuvimab / Ebanga received FDA approval in 2020.

“Advances in supportive care and therapeutics over the past decade have revolutionized the treatment of Ebola. Ebola virus disease used to be perceived as a near certain killer. However, that is no longer the case,” ​said Dr Robert Fowler, University of Toronto, Canada and co-chair of the guideline development group. 

“Provision of best supportive medical care to patients, combined with monoclonal antibody treatment—MAb114 or REGN-EB3—now leads to recovery for the vast majority of people.”

The mAbs can be used for all patients confirmed positive for Ebola virus disease, including older people, pregnant and breastfeeding women, children and newborns born to mothers with confirmed Ebola within the first seven days after birth.

Patients should receive recommended neutralizing monoclonal antibodies as soon as possible after laboratory confirmation of diagnosis.

mAb114 is a single monoclonal neutralizing antibody which binds to a conserved epitope within the glycoprotein subunit 1 (GP1) within the receptor binding domain (RBD). It was derived from memory B cells from a recovered EVD patient from the 1995 EVD outbreak in Kikwit, Democratic Republic of the Congo, approximately 11 years after infection. mAb114 exerts antiviral effects by binding and neutralizing virus particles present in circulation, thus inhibiting cell entry.

REGN-EB3 is a cocktail of three antibodies: atoltivimab, odesivimab and maftivimab, selected from a pool of antibodies generated in genetically engineered mice exposed to EBOV. The three antibodies bind to non-overlapping epitopes on the Ebola glycoprotein; atoltivimab binds the GP1 head, odesivimab targets the outer glycan cap, and maftivimab targets the conserved GP2 fusion loop. REGN-EB3 exerts antiviral effects by binding and neutralizing virus particles present in circulation, thus inhibiting cell entry. Activation of effector functions through antibodydependent cellular cytotoxicity, antibody-dependent cellular phagocytosis and antibody-dependent complement deposition are also implicated in activity of REGN-EB3.

The WHO is now calling on the global community to increase access to the two monoclonal antibodies. It notes access to both treatments remains challenging, especially in resource-poor areas.

The WHO pledges to support countries, manufacturers and partners to improve access to these treatments, and to support national and global efforts to increase affordability of biotherapeutics.

It invites manufacturers of therapeutics against Ebola to share their drugs for evaluation by the WHO Prequalification Unit, a crucial step to improve drug access for communities and countries affected by Ebola.

“We have seen incredible advances in both the quality and safety of clinical care during Ebola outbreaks,”​ said Dr Janet Diaz, lead of the clinical management unit in WHO’s Health Emergencies program.

“Doing the basics well, including early diagnosis, providing optimized supportive care with the evaluation of new therapeutics under clinical trials, has transformed what is possible during Ebola outbreaks. This is what has led to development of a new standard of care for patients. However, timely access to these lifesaving interventions has to be a priority.”

The guidance includes recommendations on therapeutics that should not​ be used to treat patients: these include ZMapp and remdesivir.

The recommendations in the latest guidance only apply to Ebola virus disease caused by Ebola virus (EBOV; Zaire ebolavirus). The WHO says there remains a need further research and evaluation of clinical interventions.

Ebola is a severe and often fatal illness caused by the Ebola virus. Previous Ebola outbreaks and responses have shown that early diagnosis and treatment with optimized supportive care —with fluid and electrolyte repletion and treatment of symptoms—significantly improve survival.

Developed according to WHO standards and methods for guidelines, and published in English​ and French, the guidelines will support health care providers caring for patients with Ebola, and policymakers involved in outbreak preparedness and response. The clinical trials were conducted during Ebola outbreaks, with the largest trial conducted in the Democratic Republic of the Congo.

The new guidance complements clinical care guidance that outlines the optimized supportive care Ebola patients should receive, from the relevant tests to administer, to managing pain, nutrition and co-infections, and other approaches that put the patient on the best path to recovery.

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