WARRENSBURG — In August, two Ebola treatments were deemed effective enough to replace ZMapp as considered the standard for treating Ebola.
One of the treatments, REGN-EB3, was developed by Regeneron Pharmaceuticals in conjunction with Biomedical Advanced Research and Development Authority, which included Melissa Willis, who grew up on a farm outside of Warrensburg and graduated from Crest Ridge High School in 1988 and University of Central Missouri in 1992.
“I am very humbled and deeply satisfied to know that something I helped to develop has worked so well against such a deadly pathogen,” Willis said. “I hope that this story encourages all those young people in the Warrensburg area to pursue their passions and dream big. You just never know where that will take you.”
Along with REGN-EB3, a treatment developed by the National Institute of Health and licensed by Ridgeback Biotherapeutics LP in 2018, mAb-114, was also proven to be a highly successful Ebola medication.
These two treatments were tested in the PALM study along with ZMapp and remdesivir, developed by Gilead Sciences.
The study began on Nov. 20, 2018, in the Democratic Republic of the Congo as part of the emergency response to an ongoing Ebola outbreak.
Patients inflicted with the disease were enrolled in one of four Ebola Treatment Centers in Beni, Katwa, Butembo or Mangina where they were randomly provided with ZMapp, remdesivir, mAb114 or REGN-EB3 for Ebola treatment.
Willis, who worked as a section chief for antiviral therapeutics at BARDA within the Department of Health and Human Services in the federal government, was tasked with working with Regeneron to develop the Ebola medication.
“Our mission was to partner with and fund companies to develop new therapeutics against pathogens that could cause pandemics or could be used in biodefense,” Willis said.
Because Ebola is a BSL-4 pathogen, it can only be worked with in very high containment.
All of the BSL-4 high containment facilities (aside from one) in the U.S. are owned and operated by the federal government.
If a company (like Regeneron) wants to test new therapeutics or vaccines against these pathogens, they must partner with the federal government to get this work done.
“This was a unique collaboration that took place during a time of great uncertainty,” Willis said. “We knew that Ebola was spreading rapidly and that it would take just one infected person on a plane to spread it to the rest of the world.”
For the treatment, a cocktail of antibodies was developed to combine biological activities and improve efficacy/outcomes, reduce potential for escape and resistance and increase the potential utility for future outbreaks as viruses evolve.
“During the Ebola response, my team and I coordinated and funded all of the testing of the antibodies developed by Regeneron that were tested in animal models in BSL-4 facilities,” Willis said. “We also helped to develop these animal models. Regeneron did all of the work on the antibodies that could be completed outside of high containment. Then, each week my team and the Regeneron team met to review the data and finally decide on the 3 antibodies that became REGN-EB3.”
Willis said that the cooperation between BARDA and Regeneron was mutually beneficial and allowed the development of REGN-EB3 to take place.
“It really was a public-private partnership because we could not have done all the work had we not worked together,” Willis said. “The BARDA team could not have done all the work Regeneron did and Regeneron could not have tested those antibodies in BSL-4 without BARDA.”
According to the World Health Organization, the 2013 – 2016 Ebola virus pandemic in West Africa resulted in more than 28,000 cases and about 11,000 deaths throughout Guinea, Sierra Leone and Liberia.
Despite being ultimately controlled, Ebola continued to pose a high risk for causing epidemics with high mortality rates.
The Democratic Republic of Congo is currently in the midst of the world’s second largest Ebola epidemic on record, with more than 2,000 lives lost and more than 3,000 confirmed infections since the outbreak was declared on Aug. 1, 2018.
“Now we know that infection with the Ebola virus is no longer a death sentence,” Willis said. “If people get treated as soon as they are exposed or upon symptom onset, most of them can be saved. Of course, if treatment is delayed and the infection is advanced the likelihood of saving the person goes down but this is the case for most deadly infectious diseases. Early treatment is always best.”
Willis left BARDA last year and had lost track of the work that was ongoing, but when she saw the results of the trial, she was surprised at how well the antibodies worked.
“I knew from the animal models that they should work, but you never really know until you test in humans whether they will work. It was a deeply satisfying feeling to see the clinical trial results,” Willis said.