Nav: Home

Study finds Ebola treatment ZMapp holds promise, although results not definitive

October 12, 2016

A clinical trial to evaluate the experimental Ebola treatment ZMapp found it to be safe and well-tolerated; however, because of the waning Ebola epidemic, the study enrolled too few people to determine definitively whether it is a better treatment for Ebola virus disease (EVD) than the best available standard of care alone. The findings from the randomized, controlled trial known as PREVAIL II appear in the October 13th issue of The New England Journal of Medicine. Initial trial findings were reported in February 2016, at the Conference on Retroviruses and Opportunistic Infections in Boston.

"Although we do not have definitive evidence that ZMapp is superior to the optimized standard of care, the results of the PREVAIL II trial are promising and provide valuable scientific data," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). "Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner."

ZMapp, developed by Mapp Biopharmaceutical, Inc., based in San Diego, is composed of three different laboratory-made proteins called monoclonal antibodies. The treatment is designed to prevent the progression of EVD within the body by targeting the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as five days after experimental infection with Zaire ebolavirus.

The study launched through a collaboration between the Liberian Ministry of Health and NIAID, known as the Partnership for Research on Ebola Virus in Liberia (PREVAIL). It later expanded to include research partners within the countries of Sierra Leone and Guinea and the French medical research organization INSERM.

The study team was led by co-principal investigators Richard T. Davey, Jr., M.D., deputy clinical director of NIAID's Division of Intramural Research; Moses Massaquoi, M.D., National Chair for Case Management at the Ebola Incident Management System in Monrovia; Foday Sahr, M.D., Brigadier General and First Surgeon General of the Republic of Sierra Leone Armed Forces; and Denis Malvy, M.D., Ph.D., head of the tropical medicine division at the University Hospital of Bordeaux and permanent senior researcher at INSERM.

The trial enrolled 72 participants of any age with confirmed Ebola virus infection from March 2015 through November 2015. The participants came from Sierra Leone (54 patients), Guinea (12 patients), Liberia (five patients) and the United States (one patient, a health care worker evacuated from Sierra Leone).

The average age of the participants was 24 years, and slightly more than half were women. Investigators closed the study in January 2016 because they could not enroll additional patients, up to the targeted 200, because of the decline in the number of new Ebola cases as the outbreak diminished.

The study sought to determine if the experimental drug ZMapp plus the optimized standard of care for treating EVD--providing intravenous fluids, balancing electrolytes needed to maintain bodily functions, and maintaining healthy oxygen and blood pressure levels--was superior to the optimized standard of care alone in reducing deaths caused by EVD. All participants received the optimized standard of care, and half were randomly assigned to also receive three intravenous infusions of ZMapp administered three days apart.

Investigators compared the number of deaths in each group at 28 days after enrollment. Thirteen deaths (37 percent mortality) were reported in the group of 35 patients who received the optimized standard of care only, while eight deaths (22 percent mortality) occurred in the ZMapp group of 36 patients. One patient left treatment early and was not included in the analysis. Although the difference between the two groups translates to a 40 percent lower risk of death for those who received ZMapp, the difference did not reach statistical significance.

Should new cases of Ebola arise, Mapp Biopharmaceutical has received funding from the U.S. Biomedical Advanced Research and Development Authority to offer ZMapp to patients with confirmed EVD in the four countries where the trial occurred under an expanded access protocol (EAP). Expanded access is a U.S. regulatory mechanism that enables an investigational drug to be made available to treat a serious or life-threatening disease for which no comparable or satisfactory alternative therapy is available. The EAP was reviewed and considered safe to proceed in the United States by the U.S. Food and Drug Administration. The company will make appropriate regulatory applications on the three West African countries that participated in PREVAIL II as well.
-end-
Financial and logistic support for the trial was provided by NIAID; INSERM; the Republic of Sierra Leone Armed Forces; the Ministries of Health and U.S. Embassy staff in Liberia, Sierra Leone, and Guinea; the U.S. Centers for Disease Control and Prevention (CDC); the CDC Foundation; the U.S. Biomedical Advanced Research and Development Authority; and the U.S. Defense Threat Reduction Agency. The trial was conducted in partnership with other academic, governmental and non-governmental agencies providing research support within the West African region. Study collaborators from the United States and Canada included experts from the University of Minnesota; Leidos Biomedical Research, Inc.; Emory University Hospital; the University of Nebraska Medical Center; Boston Medical Center; and Toronto General Hospital.

NIAID conducts and supports research--at NIH, throughout the United States, and worldwide--to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH...Turning Discovery Into Health®

Reference: R Davey et al. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection. The New England Journal of Medicine DOI: 10.1056/NEJMoa1604330 (2016).

NIH/National Institute of Allergy and Infectious Diseases

Related Ebola Virus Articles:

Tulane researchers help find possible explanation for unparalleled spread of Ebola virus
The world may be closer to knowing why Ebola spreads so easily thanks to a team of researchers from Tulane University and other leading institutions who discovered a new biological activity in a small protein from the deadly virus.
New CDISC data standard aids development of therapies for Ebola virus
The Clinical Data Interchange Standards Consortium (CDISC) and the Infectious Diseases Data Observatory (IDDO) announce the availability of a new standard to assist in the collection, aggregation and analysis of Ebola virus disease (EVD) research data.
Silence is golden -- Suppressing host response to Ebola virus may help to control infection
The Ebola virus causes a severe, often fatal illness when it infects the human body.
How do Ebola virus proteins released in exosomes affect the immune system?
Cells infected by the deadly Ebola virus may release viral proteins such as VP40 packaged in exosomes, which, as new research indicates, can affect immune cells throughout the body impairing their ability to combat the infection and to seek out and destroy hidden virus.
Blood test can predict life or death outcome for patients with Ebola virus disease
Scientists have identified a 'molecular barcode' in the blood of patients with Ebola that can predict whether they are likely to survive or die from the viral infection.
NIH scientists identify early impact of Ebola virus on immune system
A new mouse model of early Ebola virus (EBOV) infection has shown National Institutes of Health (NIH) scientists and colleagues how early responses of the immune system can affect development of EBOV disease.
Could co-infection with other viruses affect the survival of those with Ebola virus?
Could co-infection with other viruses have a detrimental affect on Ebola survival, and why did some show Ebola symptoms without having the virus?
Researchers stress the need for research on Ebola virus disease in great apes
Ebola virus disease (EVD) is a threat to human health, but it also threatens the survival of African great apes.
Antimalarial being tested as possible Ebola virus drug
The National Center for Advancing Translational Sciences (NCATS) recently awarded $596,533.00 to Collaborations Pharmaceuticals, Inc.
Antibodies from Ebola survivors neutralize virus, protect against infection in lab mice
A study by scientists at the Emory Vaccine Center, in collaboration with the biotechnology company Atreca, Inc., has found that antibodies generated from the blood of survivors of Ebola virus disease can strongly neutralize the Ebola virus in the laboratory and protect mice from a lethal viral challenge.

Related Ebola Virus Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...