With a positive test, a monster headache and fever of 101 degrees, Joanne Gieselman said “sure” when offered the chance to participate in a trial of an experimental treatment for COVID-19, the illness caused by the coronavirus. The 63-year old Redmond woman wasn’t sick enough to need hospitalization — yet — but her age and some pulmonary scarring from childhood raised her anxiety and risk levels.
“I do know people who died of this,” she said. “I was afraid this wicked virus could cause a very adverse reaction if it went into my lungs.”
So Gieselman spent an hour in a bed at EvergreenHealth’s Redmond emergency department in late August hooked up to an IV drip that contained either a placebo or an infusion of monoclonal antibodies — a promising therapy with the potential to both prevent infection and treat disease.
While the “warp speed” dash to develop a vaccine against the coronavirus gets most of the world’s attention, monoclonals are the focus of another scientific race that could help bring the pandemic under control. Many experts hope antibody drugs will serve as a bridge until vaccines are widely available — which is not likely to be before next spring or summer.
“If they are successful, monoclonal antibodies are really going to revolutionize treatment for COVID-19,” said Dr. Larry Corey, former director of the Fred Hutchinson Cancer Research Center and co-leader of a national network coordinating clinical trials on vaccines and antibodies.
The drugs are designed to mimic the body’s natural immune response on an industrial scale by delivering doses of mass-produced antibodies. Multiple trials are underway across the country and in Washington state, including the one Gieselman volunteered for. With government support, pharmaceutical companies are gearing up to begin manufacturing even before the final results are in.
Preliminary data released Sept. 16 shows lower viral levels and reduced hospitalization rates in patients who got a monoclonal antibody developed by Eli Lilly and Vancouver, B.C.-based AbCellera — and reportedly isolated from the blood of one of the first people in the Seattle area to recover from the virus. That’s also the antibody being studied at EvergreenHealth.
If the trials pan out, researchers say the drugs could offer instant protection for vulnerable groups like health care workers and nursing home residents. Monoclonal antibodies could also provide a desperately needed treatment option, including for people who don’t respond well to vaccines because of age or compromised immune systems and those who choose not to get vaccinated — which a new survey suggests could be nearly half of all Americans.
Microsoft co-founder Bill Gates calls the drugs a “wild card” that could dramatically cut the death rate. The Bill & Melinda Gates Foundation is funding a project to catalog and compare hundreds of unique antibodies from labs around the globe. The foundation has also reached an agreement to reserve manufacturing capacity to produce the complex and costly drugs for low-income countries.
“I think of vaccines and monoclonal antibodies as being really complementary to each other,” said Dr. Shelly Karuna, of “The Hutch,” who was part of a stampede of scientists who quickly pivoted to searching for and evaluating antibodies against the new virus.
Vaccines work by teaching the immune system to produce antibodies that attack a pathogen — a process that can take weeks and require multiple shots. Monoclonal antibodies skip the instruction step and deliver a ready-made immune arsenal composed of identical, manufactured antibodies selected for maximum potency against the novel coronavirus. Protection is temporary — lasting perhaps a few weeks to a few months — but instantaneous.
“You could sweep in and treat everybody in a nursing home,” Corey said.
In fact, nursing homes and assisted living centers are the setting for one of Lilly’s double-blind, controlled trials. When a resident or staff member tests positive for the virus, researchers rush in with mobile labs and administer the antibodies — or placebo — to other residents and staff to see if the treatment can fend off infection and prevent the disease from spreading.
EvergreenHealth’s Kirkland hospital was initially at the epicenter of the U.S. outbreak with the first recorded patient death and a deluge of cases from nearby Life Care Center nursing home. Now that hospitalizations have become less common in Washington, the health system was eager to take part in a separate Lilly trial to see if monoclonal antibody treatment can reduce viral loads and the severity of disease in newly infected people with mild to moderate symptoms — like Gieselman, who got her infusion two days after her initial diagnosis.
“These are folks who are just coming in,” said Anhaita Jamula, director of research for the network that includes clinics, hospitals and urgent care centers across King and Snohomish counties. “They are feeling sick, but they are not sick enough to get admitted to the hospital.”
Currently, there’s no medication to help patients like that, Jamula pointed out. The two drugs approved for COVID-19 — the antiviral remdesivir and the steroid dexamethasone — have so far only been shown to make a difference for hospitalized patients.
Harborview Medical Center and Providence Regional Medical Center Everett are both participating in trails of a two-antibody cocktail developed by Regeneron Pharmaceuticals, a New York biotech company. The Harborview experiment is focused on people who have been exposed to a family member with the virus but who aren’t yet infected themselves, Karuna explained.
The Everett hospital is involved in three antibody studies, including the same preventive trial as the Harborview site. “That’s the study I’m really excited about,” said Dr. George Diaz, chief of infectious disease for the Everett facility. “We are trying to interrupt disease transmission in the community.”
Monoclonal antibodies could be more effective than another experimental treatment called convalescent plasma, Diaz said. The latter is simply a transfusion of blood plasma from a person who recovered from the disease — so each treatment requires a separate donor. And while plasma contains a hodgepodge of antibodies and other molecules, monoclonal antibody drugs contain standard dosages proven in the lab to neutralize the virus.
As the only companies with ongoing, late-stage trials, Lilly and Regeneron are the clear front-runners in the monoclonal antibody race. But that doesn’t mean their products are the best, said Marion Pepper, an immunologist at the University of Washington who’s spent the past six months laboriously mining blood samples from 15 volunteers who had COVID-19 to understand the immune response and identify the most powerful antibodies.
“We have the tools and the techniques to find these needles in a haystack,” she said.
Pepper and her colleagues have zeroed in on several promising candidates, focusing on more mature antibody-producing cells that develop a month or more after infection and produce antibodies more precisely tailored to disable the spike protein the novel coronavirus uses to infect human cells.
“There are other antibodies that are way further ahead than ours, but we think ours might have better quality,” Pepper said. “We have a whole panel of antibodies that we know are capable of neutralizing the virus in lab culture assays, and now we’re trying to figure out what to do with them.”
She’s talking with multiple companies about how to proceed. A mix of antibodies that target different parts of the virus could be even more powerful than single monoclonals and harder for the virus to escape from even if it mutates, Pepper said.
More than 50 monoclonal antibody therapies are in development against the coronavirus, according to a recent report from two leading nonprofits, which also warned that without steps to reduce or share the costs, the drugs could be out of reach for people in the world’s poorest countries.
Seven out of the top 10 best-selling drugs globally are monoclonal antibodies — including Humira for rheumatoid arthritis and Crohn’s disease and Keytruda for melanoma and other types of cancer — and they’re all expensive.
The median cost for a year of treatment ranges from $15,000 to more than $140,000, according to the report by the International AIDS Vaccine Initiative and the British philanthropy Wellcome.
The Gates-funded Coronavirus Immunotherapy Consortium is building a library of COVID-19 monoclonals and comparing them side by side on a wide range of metrics. Companies and research labs have offered up 100 antibodies so far, and another 100 are expected, said director Erica Saphire, of the La Jolla Institute for Immunology.
“It’s going to be the largest, deepest, broadest database of how antibodies perform against the [novel] coronavirus,” Saphire said. The Gates Foundation is looking for the most potent candidates and combinations, along with those that can be easily and more cheaply produced. They’re also interested in drugs that can be formulated for delivery via injection or pill, rather than infusion.
“Their mandate to me was to look among all the different antibodies going forward and figure out which … can be used to save lives in low-income countries,” Saphire said.
It’s not clear how soon monoclonal antibody treatments could be available. Lilly and Regeneron hope to have results within the next few months, and the federal Operation Warp Speed initiative has vowed to support advance manufacture so if the trials are successful, “hundreds of thousands of doses” will be ready for deployment by this fall and winter.
Gieselman’s not sure if she will ever know what was in the dose she received — drug or placebo — let alone whether the infusion might have prevented a more severe illness. Her fever started dropping about four days after her diagnosis, but then she was slammed by several days of crushing fatigue. Nearly a month later, her only lingering symptom is a diminished sense of smell.
Her husband, who almost certainly picked up the virus from her, had a much rougher time, with more respiratory distress. Because he was out of town when he got sick, he couldn’t participate in the trial.
“That makes me wonder whether I did get the antibodies,” Gieselman said.
Either way, she’s glad she was able to contribute to the research effort.
“That’s why I was willing to be a part of this,” she said. “I thought it’s possible it could help me, but it’s also going to help others.”
(For information on the Harborview trial, call 206-773-7129; for the Providence Everett trials, call 844-552-2734. Information on the EvergreenHealth trial is available by calling 425-650-0019, or going to evergreenhealth.com/blaze-study.)
This story has been updated to correct the last name of Dr. Shelly Karuna of the Fred Hutchinson Cancer Research Center.