Seattle-area residents Ferguson Neale and Pam Pruitt are just two of more than 40 million Americans who came down with COVID-19 since the start of the pandemic. But they are hoping to make a difference.
This summer, shortly after receiving word they had tested positive, they each agreed to join a clinical trial at Fred Hutchinson Cancer Research Center for an experimental drug to knock down the virus that causes COVID-19. Each of them recovered after a mild illness.
Their willingness to be poked and prodded might help lead to a treatment that could keep COVID-19 patients out of the hospital with a simple injection — instead of an intravenous drip — of laboratory-manufactured immune proteins called monoclonal antibodies.
“It was the easiest experience,” said Neale, a 59-year-old computer systems consultant who lives with his family on Mercer Island. “They are whompin’ shots, but the only pain I felt was exposing my backside to three or four people.”
You read it right: He received an injection in each cheek of the gluteus maximus, that thick muscle better known as your butt.
It is the whole point of the trial — to see if injections of antibodies, already okayed by emergency use authorization to treat early COVID-19 cases via IV drip, can be just as effective if delivered by syringe into the fleshiest part of the shoulder or the larger muscles of the buttocks.
As a practical matter for treatment of COVID-19, this could be very important.
While IV drips of the antibody drug known as sotrovimab are now used to treat mild-to-moderate COVID-19 in high-risk patients, the number of medical facilities set up to deliver infusions of any kind is limited in a health care system already under enormous strain because of the pandemic.
“Typically, the places set up to deliver intravenous drugs are chemotherapy centers, where people are being treated for cancer and are immune-compromised. The last thing you want to do is bring in people with active COVID,” said Fred Hutch physician-scientist Dr. Adrienne Shapiro.
She is a principal investigator in the trial at the COVID-19 Clinical Research Center, or CCRC, which was set up to test treatments safely at a specialized facility, isolated from other areas of the Hutch’s South Lake Union campus.
“The real impetus is to give people treatments that can keep them out of the hospital, and to give them in less-restrictive settings,” Shapiro said. “It’s a major access issue, and an injectable treatment would be a huge convenience.”
Neale said that his bout with COVID-19 reminded him of how it feels flying a red-eye across the country.
“For the first week, it was as if every morning started like I’d just gotten off the plane,” he said. It took a full month for him to feel fully recovered, back to his routines of swimming and bicycling.
Coincidentally, both Neale and Pruitt, 69, of Mill Creek, were early breakthrough cases. These are people who contracted symptomatic COVID-19 despite being fully vaccinated against it. The two are among 17 CCRC participants in the study, known as COMET-TAIL, which is sponsored by sotrovimab developer Vir Biotechnology, in collaboration with pharmaceuticals maker GlaxoSmithKline.
The injectable antibody trial began shortly after another Vir study that used IV infusion, COMET-ICE, was stopped early because sotrovimab was quickly found to be very effective. It had shown a 79% reduction in hospitalizations or death for those who received the IV drug compared to those receiving a placebo. The CCRC was a participating site in that study as well, enrolling 13 participants.
Update: Shapiro is the corresponding author of a paper published on Oct. 27, 2021, by the New England Journal of Medicine reporting on the results of the COMET-ICE trial, which are summarized in this Fred Hutch press release about the article.
Unlike COMET-ICE, the newer COMET-TAIL study has no placebo arm. Every participant received a shot in the buttocks or shoulder or was randomly assigned to receive the active drug in an IV infusion.
Participants assigned to the injection were randomly chosen to receive either the full dose in two shots (one in each cheek), or a half dose with a single shot in the butt or two shots in the arm. Each injection is completed in about five seconds. Because an intravenous drip requires the active antibodies be mixed with about a quarter cup of saline solution, it takes about 15 minutes to deliver the IV infusion, plus a half hour of observation afterward.
Shots require much less liquid to deliver the same dosage of antibodies as the IVs. In fact, the shot uses about the same volume of fluid as there is ink in a ballpoint pen, Shapiro said.
Because antibodies are natural occupants of our bloodstreams, Shapiro explained that participants feel no sting or pain during infusions or injections. Nor does the small amount of fluid cause swelling in the fleshy, muscled target sites.
“It’s going to a very forgiving space,” she said. “There is room for the fluid to go in.”
Pruitt, a retired auditor, a local newspaper columnist and former five-term mayor of Mill Creek, was assigned to receive the intravenous dose, part of the group of study participants who serve as experimental controls. Their rate of protection from serious COVID-19 disease will be compared with those who were assigned the shots.
Pruitt has type 2 diabetes and thus is at higher risk for more serious COVID-19. It did not matter to her how the drugs were administered.
“I am fully grateful to have gotten both the vaccine and the antibodies,” she said. “It kept me out of the hospital, and it kept me out of the morgue.”
In July, Pruitt experienced fever, chills and nausea, and thought at first it was some sort of foodborne illness. Through routine contact tracing, she was referred as a potential clinical trial candidate to Fred Hutch, and just three days later she received her antibodies as part of the trial.
“Getting the infusion was so easy, I had to complain I didn’t even get a bruise,” she said. “How can I run around town being a martyr for science when I didn’t even have a bruise?”
Although Pruitt lost her senses of taste and smell, they came back within a few weeks and today she feels almost fully recovered. She still experiences some fatigue and brain fog. “This could have gone bad very quickly,” she said.
In addition to receiving the antibodies at Fred Hutch, Pruitt, Ferguson and other participants in the trial regularly return for checkups and to have their blood tested to measure their immune responses to the treatments. Pruitt said she has been back seven times since the July 14 infusion and will continue to report in through the end of December.
Meanwhile, CCRC is also hosting clinical trials of molnupiravir, an experimental antiviral drug designed to take the edge off early COVID-19 infections with a five-day course of pills. If it works, it could become for COVID-19 what the drug Tamiflu is for influenza — an intervention that can be taken at home and potentially take days off the recovery time.
Based on results of earlier, smaller trials, the White House has signed a contract with molnupiravir developer Merck to supply 1.7 million courses of the drug should it eventually receive emergency use authorization or approval by the Food and Drug Administration. The company is investing its own money to scale up production of molnupiravir and, according to its press release, “expects to have more than 10 million courses of therapy available by the end of 2021.” All that depends on the findings of the current Phase 3 clinical trial, known as MOVe-OUT.
Fred Hutch physician-scientist Dr. Elizabeth Duke is the principal investigator at the CCRC site for that trial. The study is designed to enroll 1,550 recently infected, nonhospitalized participants worldwide. Each must have at least one risk factor associated with a poor outcome for COVID-19 including diabetes, heart disease or active cancer. So far, eight of the 20 slots allotted for the trial at the CCRC have been filled.
Duke said the research into oral antiviral drugs like molnupiravir is driven by the vision that patients might be able to access the pills quickly after testing positive for the virus, perhaps at the same clinics that provide tests.
“The earlier you treat a viral infection, the better the outcome you generally have,” she said.
Molnupiravir is designed to be incorporated into the genome of RNA viruses, increasing the frequency of mutations during replication and ultimately killing the virus. What excites researchers like Duke is that the drug appears to be “pan-active” — working against a variety of RNA viruses. That means, potentially, that this drug or a similar one might be effective against a range of serious respiratory viruses such as influenza, parainfluenza and respiratory syncytial virus, or RSV.
The notion that antiviral drugs can be mustered to block future pandemics has caught the attention of the Biden administration, which in June announced plans to invest $3 billion from the pandemic-related American Rescue Plan to speed the discovery, development and manufacturing of COVID-19 treatments. In addition to evaluating 19 potential antiviral medications, it will allocate up to $1.2 billion to support Antiviral Drug Discovery Centers, or AViDDS, groups of biomedical research organizations whose goal is to develop new antiviral medications that might fend off the next pandemic.
Dr. Rachel Bender Ignacio, who is medical director for both the CCRC at Fred Hutch and director of the University of Washington’s AIDS Clinical Trials Unit at Harborview Medical Center, said the global interest in pandemic drug development will provide opportunities to researchers in both academic and industry settings.
She said that while drug companies have the resources to get new drugs into the marketplace quickly, academic researchers may be best suited to try out new ideas.
“The Hutch could be one of these centers for looking new antivirals,” she said. “We should be looking at investigator-initiated ideas.
“If these antiviral agents are successful, they will not only help people feel better faster, but it could shorten isolation and quarantine periods. Household contacts might be able to return to work once treated, and high-risk people will be able to avoid hospitalization,” Bender Ignacio said.
Sabin Russell is a former staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and he wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT and a freelance writer for the New York Times and Health Affairs.
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