USAMRIID photo

John Dye, viral immunology branch chief, works in the laboratory at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick. Dye is the leader of a team that conducted a study with nonhuman primates involving the drug ZMapp, an experimental treatment for Ebola patients.

Nearly a year after the first multi-drug Ebola trial began in the Democratic Republic of Congo, the World Health Organization announced that only two of the four drugs would continue to be tested.

The reason: Two of the treatments had more efficacy than the others. But while only two were continuing in the trial — mAb114, developed by the National Institute of Allergy and Infectious Diseases, and REGN-EB3, created by the pharmaceutical company Regeneron — all four drugs have a connection to Frederick.

The four therapies were created with help from the U.S. Army’s Medical Research Institute of Infectious Diseases. Depending on the treatment, USAMRIID staff may have helped do in vitro testing with cultures, and then live animals. Or it might have helped develop some of the antibodies, said John Dye, chief of viral immunity at USAMRIID.

Although not all four drugs will continue to be part of the study, Dye said all of them had some efficacy.

“So it’s a win-win-win-win,” he said.

Available data from the trial is preliminary and limited, but it showed a 53 percent mortality rate for those treated with Gilead’s remdesivir, a 49 percent mortality rate for Mapp Biopharmaceutical’s ZMapp, a 34 percent mortality rate for those treated with NIAID’s mAb114 and a 29 percent mortality rate for those who received REGN-EB3, according to Helen Branswell’s reporting in STAT.

The overall mortality rate for Ebola is 67 percent, according to the STAT article.

Gilead’s remdesivir was tested at USAMRIID. Mapp Biopharmaceutical’s ZMapp is made up of three antibodies, one of which was created at USAMRIID, Dye said.

Despite not continuing in the second branch of the trial, Gilead is continuing to study remdesivir’s use for Ebola treatment, according to a statement from the company.

“We believe remdesivir may still have benefit for future outbreaks of Ebola, depending on the viral strain, the severity of disease progression and the potential for both single agent and combination treatment approaches,” according to the statement.

One of the studies will look at the drug in male Ebola survivors to prevent future transmission. Another early study is looking at the drug’s effects against other viruses.

Remdesivir and ZMapp were used to help treat those infected with Ebola in the 2014 outbreak.

USAMRIID also tested mAb114. For that drug, USAMRIID did in vitro testing, meaning that researchers there tested the drug in a culture. To see if the drug worked, researchers looked to see if it reduced the amount of virus in infected cells.

USAMRIID also did mAb114 testing in animal models, typically mice, guinea pigs and then primates. Products are often tested multiple times at USAMRIID, Dye said.

“Ebola is a rare and deadly disease, which is why it is important to develop safe and effective countermeasures that can improve patients’ chances of survival. ... NIAID scientists collaborated with USAMRIID staff, who played a pivotal role and advanced the research leading to the development of the investigational treatment mAb114,” according to an emailed statement from NIAID.

For Regeneron’s REGN-EB3, USAMRIID helped develop antibodies used in the drug, although none were created at USAMRIID. It also performed testing, which was completed around 2017-2018, Dye said.

Regeneron is “very happy, proud” to see the efficacy of REGN-EB3, said Christos Kyratsous, vice president of research, infectious diseases and viral vector technologies. The company plans to send more of the drug to the Democratic Republic of Congo for the extended trial.

USAMRIID is one of the few laboratories with biosafety level 4 laboratories, the containment level required to test Ebola treatments, which is why its partnership can be critical to Ebola research, Kyratsous said.

USAMRIID is not currently working on any of the drugs as they have moved past the point where USAMRIID would be involved. Unrelated, USAMRIID is currently working to regain its ability to do research in its biosafety level 3 and 4 labs after receiving a cease and desist letter from the Centers for Disease Control and Prevention.

USAMRIID helped with each of the treatments because of its mission to protect military personnel, especially those who might go into areas where an outbreak occurs.

“And we’re just really pleased that the work that we’re doing here has a more global impact in that it’s able to help in an outbreak situation like this that is totally unrelated to the military,” Dye said.

The Ebola drugs have been a long time coming, Dye said, as proper research, development and testing takes several years.

“And I would say that it justifies the years of research that we have spent, and it solidifies the importance of our role as an institute in not only the military community but the global community, and to have a product that you have evaluated, developed and tested actually making a difference in the real world, it creates a feeling inside of you that it’s hard to explain,” Dye said. “It really makes you feel very justified and worthwhile about what you’re doing.”

Follow Heather Mongilio on Twitter:

@HMongilio.

Heather Mongilio is the health and Fort Detrick reporter for the Frederick News-Post. She can be reached at hmongilio@newspost.com.

(6) comments

public-redux

In “Outbreak”, the movie with Dustin Hoffman about an ebola-ish virus,there is a brief scene in Frederick. Hoffman’s character and his wife are getting a divorce and their Frederick house is for sale. There is an ‘Ausherman” sign on the front lawn. Nice touch!

gabrielshorn2013

Yes, however the scene showing the helicopter swooping in over the Ft. Detrick gate arch was faked. That location doesn't exist on base.

public-redux

Ah, good catch.



There is a scene in a West Wing episode that shows the yellow arch bridge on I-70 between Frederick and Hagerstown as being en route to Camp David. While one could go to CD that way, I doubt that is the usual approach.

threecents

I hope the FNP does a follow-on article on USAMRIID contributions to the Ebola vaccine that has limited the spread of the current epidemic and the challenges involved in getting the vaccine where it needs to be. And perhaps there could be a series of articles on the many people from Fort Detrick who went to Africa to help contain Ebola outbreaks.

lynnemezzo

Agreed! There were many who participated in the early Ebola research, as well as research into the numerous hemorrhagic fevers from Africa, i.e. Marburg, Riff Valley fever, etc.

gabrielshorn2013

That's great news for USAMRIID. Was the CDC's "cease and desist" letter lifted?

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