New Drug Investigation in the Treatment of Ebola

Joey Spada, Mercer University College of Pharmacy

The ebola outbreak has resulted in more than 28,000 confirmed cases of ebola virus disease (EVD) and more than 11,000 deaths. [1]   Poor healthcare infrastructures and a lack of therapeutic agents and vaccines have been stated to play significant roles in the magnitude and spread of the outbreak. [2]  ZMapp is an available treatment that mixes three monoclonal antibodies directed against the surface glycoprotein of ebola virus (EBOV).  

A Randomized, Controlled Trial of ZMapp for Ebola Virus [2]
Design Randomized, controlled; N= 72
Objective To determine whether the addition of ZMapp to the current standard of care for EBOV improved patient outcomes
Study Groups Current standard of care (n= 36); ZMapp + current standard of care (n= 36)
Methods Patients of any age who had positive test results for EBOV on a PCR assay were included.  Randomization was stratified according to PCR cycle-threshold value (<22 cycles vs >22 cycles) and location (Liberia and Sierra Leone vs Guinea vs the United States), resulting in 6 strata.  ZMapp treatment was generally begun within 12-24 hours after randomization and consisted of three separate IV infusions of ZMapp (50mg/kg of body weight), administered every third day (patients received at total of nine injections over the entire course of treatment).
Duration March 2015 – December 2015
Primary Outcome Measure 28-day mortality
Baseline Characteristics All patients Current standard of care alone Current standard of care plus ZMapp
Mean age, yrs ± SD 26.1 ± 17.4 27.9 ±16.4 24.3 ± 18.3
Age < 18 yrs, n (%) 23 (32) 8 (22) 15 (42)
Female, n (%) 40 (56) 17 (47) 23 (64)
Black, n (%) 60/61 (98) 31/32 (97) 29/29 (100)
Work involving contact with persons with EVD, n (%) 5 (7) 5 (14) 0
First onset of disease, mean days ± SD 4.2 ± 2.7 4.4 ± 2.9 3.9 ± 2.5
Days since first seen by clinician, mean days ± SD 1.8 ± 1.6 1.9 ± 1.6 1.8 ± 1.5
RT-PCR cycle-threshold value, mean days ± SD 23.9 ± 5.3 23.8 ± 5.4 24.1 ±  5.3
RT-PCR cycle-threshold value <22, n (%) 30 (42) 15 (42) 15 (42)
Favipiravir use, n 12 5 7
Results Current Standard of Care Alone Current Standard of Care plus ZMapp
Patients alive, n 22 28
Patients who died, n 13 8
Patients lost to follow-up, n 1 0
28-day mortality, % 37 22
Adverse Events Common Adverse Events: fever (14% with first infusion) and hypotension (11% with first infusion)
Serious Adverse Events: None
Percentage that Discontinued due to Adverse Events: 9%
Study Author Conclusions ZMapp plus the standard of care was suggested to be superior to the current standard of care alone even though the prespecified probability for superiority of 97.5% was not met.

 

The 2014-2016 Ebola outbreak in West Africa has dominated recent news cycles.  The lack of therapeutic agents and vaccines with proven efficacy against EVD has contributed to the magnitude of the ebola epidemic.  Even though the results did not meet the prespecified probability significance threshold, this trial suggested that ZMapp + current standard of care may prove to be beneficial moving forward in ebola treatment; however, further research is needed to draw more conclusive results.  

References:

  1.  Ebola data and statistics: situation summary. Geneva: World Health Organization, January 20, 2016 (http://apps.who.int/ gho/data/view.ebola-sitrep.ebola-summary -20160120?lang=en).
  1.  A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection. N Engl J Med. 2016;375(15):1448-1456.

 

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