Monoclonal antibodies could fill treatment gap until vaccines arrive, but at a cost

SEATTLE – 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. She wasn't sick enough to need hospitalization — yet — but her age, 63, and some pulmonary scarring from childhood raised her anxiety and risk levels.

"I do know people who died of this," she said.

So she spent an hour 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 gets most of the 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. With government support, pharmaceutical companies are gearing up to begin manufacturing even before the final results are in.

Preliminary data show 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, 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. Monoclonal antibodies skip the instruction step and deliver a ready-made immune arsenal composed of identical, manufactured antibodies selected for maximum potency. 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.

Currently, there's no medication to help people who are sick but not sick enough to be admitted to the hospital like that, said Anhaita Jamula, director of research for the network. 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.

Monoclonal antibodies could be more effective than another experimental treatment called convalescent plasma, said Dr. George Diaz, chief of infectious disease for the Everett facility. 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.

More than 50 monoclonal antibody therapies are in development against the coronavirus, said a recent report from two leading nonprofits.

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.