In the 1995 movie “Outbreak,” doctors whip up a serum from monkey blood in just days to cure people of the fictional Motaba virus. In the more recent “Maze Runner” series, the teenaged protagonists find a cure for a zombifying virus in the blood of a companion who was immune.
Blood-plasma-based cures aren’t just the stuff of movies. There’s plenty of science to back the idea that blood products from survivors of viral diseases — containing antibodies primed against the virus — can jump-start an immune response in new patients. Most recently, the state-owned China National Biotec Group said it had successfully treated Covid-19 coronavirus patients with plasma from survivors.
“It has been something that has been tried in every type of outbreak that I can remember,” said Amesh Adalja, an emergency medicine specialist and senior scholar at the Johns Hopkins Center for Health Security.
But while the approach can work in a pinch, it has never been a long-term fix. In confronting the Covid-19 pandemic, drug makers instead are racing to produce high-tech derivatives in the form of monoclonal or polyclonal antibodies engineered to home in on pieces of the coronavirus. Scientists view them as likely to be both safer and more targeted, but they have yet to provide a Hollywood ending to any outbreak.
It takes time to engineer and purify these antibodies — and past epidemics have often waned before the drugs were ready. They also present myriad logistical hurdles: They have to be kept cold, for instance, and must be infused into patients rather than swallowed. And they’re expensive.
“Perhaps we all have grown up with movies and books and whatnot that have given us the impression that we can find solutions to these kinds of things very rapidly, but in the real world it does take some time,” said Eddie Sullivan, president, CEO, and co-founder of SAB Biotherapeutics, a company that produces therapeutic antibodies in genetically engineered cattle.
During the 2014-2016 Ebola epidemic in West Africa, a drug called ZMapp, based on a cocktail of antibodies against Ebola virus, was rushed into patients and looked promising enough to encourage the field, though the outbreak ended before the treatment was proven effective. Then last year, monoclonal antibodies made by Regeneron Pharmaceuticals and the National Institute for Allergy and Infectious Diseases may have helped control the outbreak in the Democratic Republic of the Congo, about doubling survival in Ebola patients in a landmark clinical trial.
“The success that we had with Ebola monoclonal antibodies has people thinking this is the quickest way we can get a countermeasure for Covid-19,” said Adelja.
Now two companies say they hope to have treatments for Covid-19 ready in record time.
Japan-based Takeda Pharmaceutical says its unit devoted to plasma-derived therapies could have a product ready for quick approval to fight the coronavirus. New York-based biotech Regeneron has said it can be ready to test hundreds of potential antibodies in Covid-19 patients by early summer. The company’s shares soared on the news even as the stock market as a whole tanked on pandemic fears.
Government labs are also working to develop monoclonal and polyclonal antibodies against Covid-19 disease. Biogen and Vir Biotechnology have teamed up to make their own versions, while antibody specialist AbCellera has won support from Eli Lilly to generate candidate antibodies from the blood of one of the first U.S. survivors of Covid-19.
They’ve worked “amazingly fast,” said Larry Zeitlin, one of the co-founders of ZMapp maker Mapp Biopharmaceutical.
Such announcements have given hope to a public frightened by the prospect of a pandemic that will almost certainly sicken millions and that has forced the closure of schools, businesses, and restaurants.
But they may also be giving a misleading appearance that a quick cure is just around the corner.
Zeitlin knows what it feels like to have such hopes dashed, after having watched the West African Ebola epidemic fade out before ZMapp could be properly tested, and then seeing the product completely dropped after it did not appear to help patients during the DRC epidemic.
The federal government has supported the development of antibody-based treatments through the Defense Advanced Research Projects Agency (DARPA) and NIAID, but they are still at early stages, said Zeitlin. “If we had another couple of years of some of these programs, I think we’d be better suited to benefit coronavirus patients,” he said.
In addition, what worked against Ebola isn’t necessarily going to be applicable to Covid-19. It takes time, said John Dye, chief of viral immunology at the U.S. Army Medical Research Institute of Infectious Diseases, to isolate the antibodies that are expected to best respond to the pathogen, then generate enough of them in a plant or animal to test them in people.
Generating enough to treat patients is even harder, said Zeitlin, even with speedier new platforms. “They are not going to be able to make enough antibody for a million patients,” he predicted. That means the treatments will be reserved for only the sickest of patients.
“It would be for those individuals who are most likely on a ventilator in a hospital, hooked up to an IV line to receive these treatments,” said Dye.
Antibody treatments are far more expensive than pills, although it’s too early to say what any of the potential treatments for Covid-19 would cost.
Plus, the antibody products are difficult to ship, requiring special storage and refrigeration.
“They are not pills and are not orally bioavailable,” said Zeitlin. They must be infused. Companies are working to develop injections or even dermal patches to deliver monoclonal antibodies, but that work is years away from bearing fruit.
Patients can have infusion reactions, and must be monitored. That means using hospital beds and having trained staff on hand at a time when hospitals, emergency rooms, and critical care units will be overwhelmed with coronavirus patients.
And there is some troubling evidence that antibody therapies could be counterproductive. “Sometimes antibodies can enhance infection,” Zeitlin said. It’s a well-known effect with dengue virus, and an international study published in February showed that an antibody targeted to neutralize MERS, another coronavirus, actually helped it infect cells.
The Covid-19 virus appears to cause much worse disease in the elderly, and people with underlying conditions. While older cancer patients have fared relatively well when given cancer immunotherapies, it’s not known whether stimulating the immune system will work as well against an infectious disease in older people. “The population that would be receiving any of these treatments is not the same population that will have been receiving them in Phase 1 trials,” said Dye.
New treatments are generally tested in younger, healthier people, and the people likely to receive the treatments in real life would have underlying conditions such as kidney disease, diabetes, and high blood pressure. It’s not clear how their bodies might respond to an antibody treatment.
SAB’s Sullivan, who hopes to start testing a Covid-19 product soon, said regulatory shortcuts are helping to speed up what is usually a linear, step-by-step process.
“There is a tremendous effort going on across all of the stakeholders that are involved in developing, testing, and clinical trials to try and be as efficient as possible,” Sullivan said. “Even with that, it will take some time.”
There’s no doubt that efforts to produce vaccines and drugs for Covid-19 are speeding along in record time, said Dye. But that will not translate into instant miracles.
“We are still in very early stages of understanding,” he said. “When people talk about [accelerated] timelines, it becomes very concerning to me, because science doesn’t always work on a timeline.”