Ebola virus disease – Democratic Republic of the Congo :: Ebola treatments approved for compassionate use in current outbreak :: Consultation on Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola virus disease

 
Milestones :: Perspectives

 
EBOLA/EVD  [to 9 Jun 2018]
http://www.who.int/ebola/en/

Disease outbreak news
6 June 2018
Ebola virus disease – Democratic Republic of the Congo
[Excerpt]
Since the last Disease Outbreak News on 30 May 2018, two additional cases have been laboratory confirmed for Ebola virus disease (EVD) in the Democratic Republic of the Congo; both cases were reported from Iboko Health Zone. Recently available information has enabled the classification of some cases to be updated1 .
…Since the launch of the vaccination intervention on 21 May, a total of 1199 people have been vaccinated in Wangata (577), Iboko (323) and Bikoro (299). Populations eligible for ring vaccination are front-line health professionals, people who have been exposed to confirmed EVD cases (contacts) and contacts of contacts…

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WHO: Ebola treatments approved for compassionate use in current outbreak
6 June 2018
On 4 June, an ethics committee in the Democratic Republic of the Congo (DRC) approved the use of five investigational therapeutics to treat Ebola, under the framework of compassionate use/expanded access. This is the first time such treatments are available in the midst of an Ebola outbreak.
Clinicians working in the treatment centres will make decisions on which drug to use as deemed helpful for their patients, and appropriate for the setting. The treatments can be used as long as informed consent is obtained from patients and protocols are followed, with close monitoring and reporting of any adverse events.
Four of the five approved drugs are currently in the country. They are Zmapp, GS-5734, REGN monoclonal antibody combination, and mAb114.

Consultation on Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola virus disease – Notes for the Record
Undated
[Excerpt]
A group of independent scientific experts convened by the WHO for the purpose of evaluating
investigational therapeutics for Ebola virus disease (EVD) during the current outbreak, 17 May 2018
Experts:
Dr. Edward Cox (Chair), Dr. Annick Antierens , Dr. Sina Bavari, Dr Gail Carson, Dr. Marco Cavaleri, Dr. Rick Davey, Dr. Robert Fowler, Prof. Stephan Guenther, Prof. Stuart Nichol, Dr. Tim O’Dempsey, Prof. Ross Upshur, Prof. Jean-Jacques Muyembe* , Prof. Steve Ahuka Mundeke*, Dr. Daniel Bausch* (*Unable to attend but reviewed the statement prior to its finalization)

There are many pathogens for which no proven effective intervention exists. For some pathogens there may be interventions that have shown promising safety and efficacy in the laboratory and in relevant animal models but that have not yet been evaluated for safety and efficacy in humans. Under normal circumstances, such interventions undergo testing in clinical trials that are capable of generating reliable evidence about safety and efficacy. However, in the context of an outbreak characterized by high mortality, it can be ethically appropriate to offer individual patients investigational interventions on an emergency basis outside clinical trials.

The WHO developed an ethical framework known as Monitored Emergency Use of Unregistered Interventions (MEURI1.) which established the following criteria to be met for access to investigational therapeutics for individual patients outside of clinical trials:
1) no proven effective treatment exists;
2) it is not possible to initiate clinical studies immediately;
3) data providing preliminary support of the intervention’s efficacy and safety are available, at least from laboratory or animal studies, and use of the intervention outside clinical trials has been suggested by an appropriately qualified scientific advisory committee on the basis of a favourable risk–benefit analysis;
4) the relevant country authorities, as well as an appropriately qualified ethics committee, have
approved such use;
5) adequate resources are available to ensure that risks can be minimized;
6) the patient’s informed consent is obtained; and
7) the emergency use of the intervention is monitored and the results are documented and shared in a timely manner with the wider medical and scientific community.

…A concise summary of key points from the expert panel’s deliberations include the points listed below. The panel noted that the available evidence for these investigational therapies was, in general, well below the usual level evidence for formulating recommendations. Panel members were free to express their viewpoints and contrary views were listened to respectfully.

:: ZMapp (a monoclonal antibody cocktail) – The available data, including the data from a
randomized controlled trial of ZMapp in patients with EVD, provide the highest quality data for
the use of ZMapp under MEURI, where the panel assessed that the benefits outweigh the risks.

:: Remdesivir (GS-5734) (an antiviral drug) – The available data support use under MEURI, however there should be concerted efforts made to study Remdesivir in appropriate clinical trials to assess its benefits and risks for treatment of patients with EVD.

:: REGN3470-3471-3479 (a monoclonal antibody cocktail) – The data were found to be very promising and support use under MEURI in settings where ZMapp or Remdisivir are not
available. However, there should be concerted efforts to study REGN3470-3471-3479 in
appropriate clinical trials.

:: Favipiravir (an antiviral drug) – The experts discussed the available data2 for Favipiravir and noted considerable uncertainty as to whether it provides benefits for patients with EVD. It is important to conduct appropriate clinical trials to establish whether it provides benefits to
patients or not. MEURI of Favipiravir may be considered in select circumstances where use of
ZMapp or Remdesivir or REGN 3470-3471-3479 are not available. Its use is complicated by
dosing selection3 for treatment of EVD.

:: Review of mAb 114 (a monoclonal antibody) – mAb114 is currently in very early stages of
development. The limited early data look potentially promising but more data are needed from
clinical trials before recommending its use for MEURI.
:: The panel affirmed the importance of moving to appropriate clinical trials as soon as possible. WHO is currently developing clinical trial designs to evaluate one, two or more candidate investigational therapeutics and assess which are beneficial to patients with EVD. WHO and partners are in active communication with product manufacturers as well as with the national authorities to expedite preparedness for clinical trials…

2 In total more than 200 EVD patients have been treated with Favipiravir, most at the JIKI doses. Designs included historical controls, and retrospective observational studies.
3 The required dosing regimen is uncertain following publications indicating plasma concentrations being low in the JIKI trial. Therefore, further dose ranging studies should be performed to assess concentrations and tolerance at higher doses.