Evusheld to prevent COVID-19 is available to Arizonans with weakened immune systems
The COVID-19 vaccine may be less effective in certain people with weakened immune systems, but a new treatment called Evusheld, now available in Arizona, is providing some hope for better protecting those individuals.
Ideally, an immunocompromised person who has received Evusheld and is exposed to the SARS-CoV-2 virus that causes COVID-19 will be equipped with enough defenses to keep viral invaders of most variants at bay, just like a healthy, vaccinated person would.
That's a huge step for people with weakened immune systems, such as those undergoing cancer treatment or people who have received an organ transplant. Those patients are at higher risk of having an inadequate antibody response to the COVID-19 vaccine, are more vulnerable to severe breakthrough COVID-19 infections than healthy individuals and are more likely to have spent the past two years of the pandemic isolated in their homes with little to no contact with the outside world.
The supply of Evusheld is limited across the U.S. While patients in some parts of the country have cited problems obtaining the treatment, state health officials in Arizona maintain that for now, there's an adequate supply here. However, it's unclear whether all Arizonans who would qualify for Evusheld are aware that it's available.
Joy Hoeffler, a 42-year-old Prescott resident who has a compromised immune system because of the medication she takes for a rare autoimmune disease, said she found out about Evusheld through the news and social media, not from any public health entities or medical providers.
She's been regularly checking a government website that lists facilities where Evusheld is available and it wasn't until Friday that her local hospital — Yavapai Regional Medical Center — made the list. She's expecting to get her injections there soon.
"When I saw it was up here and I could probably get a dose, I was very excited, and relieved and happy," she said.
Thirty-six hospitals and clinics in Arizona were offering AstraZeneca's Evusheld as of Monday, according to a therapeutics online locator maintained by the U.S. Department of Health and Human Services.
Among those locations are Banner Boswell Medical Center in Sun City, Hu Hu Kam Memorial Hospital in Sacaton on the Gila River Indian Reservation, the Mayo Clinic in Phoenix and Tucson Medical Center in Tucson.
Evusheld has an emergency use authorization that was approved Dec. 8 by the U.S. Food and Drug Administration. It is a monoclonal antibody treatment consisting of two drugs — tixagevimab and cilgavimab — for the prevention of COVID-19 in certain adults and pediatric individuals who are 12 years of age and older weighing at least 88 pounds.
Yet unlike other monoclonal antibody therapies, Evusheld is administered via two consecutive injections to the buttocks area (at the same appointment) rather than via an infusion into the bloodstream. FDA officials say the treatment may be effective for pre-exposure prevention for six months. It's not authorized for the treatment of COVID-19 or for post-exposure prevention.
The FDA's emergency use authorization allows for two groups of people to receive Evusheld:
- Individuals with moderate to severely compromised immune systems because of a medical condition or because of taking immunosuppressive medications or treatments who may not mount an adequate immune response to the COVID-19 vaccine.
- People who can't get the COVID-19 vaccine because of a history of severe adverse reactions to the COVID-19 vaccine and/or components of the available vaccines.
Evusheld is not a substitute for vaccination, said Qiang Chen, a professor in the School of Life Sciences and at the Biodesign Institute at Arizona State University.
Not only does vaccination induce a much broader spectrum of protection, but antibody therapeutics are so expensive that they would be logistically difficult to produce at the same scale as vaccines.
Still, Chen said, for the people Evusheld is intended to protect, the technology is effective.
“For people with compromised immune system(s) and for people who couldn't get immunization, this will be very useful,” he said.
Patients need a prescription for Evusheld
Health providers at the Mayo Clinic in Arizona are proactively screening at-risk patients and reaching out to them to schedule injections of Evusheld if they are interested, spokesperson Jim McVeigh wrote in an email.
"We’ve distributed only a small amount of doses to at-risk Mayo Clinic patients since mid-January," he wrote. "At this point we have provided it to Mayo Clinic patients who meet the FDA Emergency Use Authorization criteria, which include patients in active treatment for certain types of cancer, advanced HIV infection, some solid-organ transplants and other immunosuppressive conditions."
Officials with Banner Health, which is Arizona's largest health care delivery system, say Banner patients must meet approved criteria and have a doctor's order to receive Evusheld.
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"Like other health care organizations, Banner has a limited supply of Evusheld," Banner spokesman David Lozano wrote in an email. "We don’t actively promote this medication directly to a patient, but instead work with their physician since it does have strict criteria and requires a doctor’s order."
Patients getting the treatment at Banner locations are those who are moderately to severely immunocompromised because of a medical condition or because of immunosuppressive treatments such as cancer treatments, officials said.
Also, if a patient is not able to have a COVID-19 vaccine because of medical reasons, they may be given Evusheld instead, Lozano wrote.
At Phoenix Children's Hospital, supply is limited so Evusheld will initially be offered only to the most immunocompromised patients who are at highest risk of developing COVID-19 complications if they are exposed to the virus, even after vaccination, said infectious disease specialist Dr. Wassim Ballan.
That group of patients includes those undergoing hematology/oncology treatment and bone marrow transplants, Ballan wrote in an email. After that, it will be offered to patients who are undergoing various treatments that prohibit them from mounting a sufficient antibody response from their recommended COVID-19 vaccine.
"Clinical teams are working to identify eligible patients who are most at-risk; we will then reach out to the families of eligible patients," Ballan wrote. "We hope to administer this very soon to our most immunocompromised patients, so they can get the additional protection they need."
The federal government has been supplying Arizona with Evusheld since mid-December, according to officials with the Arizona Department of Health Services.
Supplies of Evusheld are going to Arizona health care facilities that have expressed an interest in the treatment, serve a large proportion of immunocompromised patients and have completed onboarding with a federal allocation panel, state health department spokesman Tom Herrmann wrote in an email.
The possible side effects of Evusheld include hypersensitivity reactions including anaphylaxis; bleeding at the injection site; headache; fatigue and cough. It's unclear whether Evusheld caused adverse cardiac events experienced by some of the clinical trial participants, since all had risk factors, FDA officials said.
Evusheld antibodies can prevent the COVID-19 virus from entering cells
Antibodies are proteins that are critical to helping the body fight disease. In a person whose immune system functions normally, special cells called B-cells produce antibodies that bind to the surface of the virus that causes COVID-19 and prevent it from entering cells, ASU's Chen explained.
“Basically, (the cell is) like a lock, and the spike protein of the virus is like a key, so (the virus) can open the door into the cells,” Chen said. When antibodies bind to that key, however, they change the virus’ shape and prevent it from unlocking the door.
The synthetic antibodies in Evusheld, called monoclonal antibodies, are very similar to naturally-produced antibodies. But instead of B-cells producing them, Evusheld puts them directly into the body, since an immunocompromised person’s B-cells might not work correctly or may be inhibited by certain medications.
Evusheld could mean more freedom for immunocompromised people, but it still needs further development to make it more effective, explained Chen, who has previously worked on vaccine and therapeutic developments for Ebola, Zika and other viruses.
Evusheld doesn’t provide quite as broad or adaptable a response as one produced by a non-immunocompromised person, and the technology is expensive.
When someone without a weakened immune system encounters the SARS-CoV-2 virus, they don’t just produce one or two types of antibodies. Instead, Chen said, their B-cells spit out a spectrum of antibodies in slightly different shapes.
Those differently shaped antibodies may not all be as potent as the ones in Evusheld, but some of them might come in handy against, say, a viral variant beyond delta.
While Evusheld still works against the omicron variant, it is significantly less potent than it is against the delta variant, according to data from an open-source database on variants and therapeutics provided by AstraZeneca. And a recent preprint suggests that Evusheld may not be able to neutralize BA.2, the sister variant of omicron sometimes called “stealth omicron,” which has not taken off in Arizona but has surged in other parts of the world.
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What’s more, although the antibodies in Evusheld have been designed to last a bit longer than natural antibodies, they don’t have another important feature of the naturally occurring version that has been helping us stave off variants like omicron. It’s called the effector function, and Chen and his team are trying to incorporate its benefits into Evusheld.
Antibodies are illustrated in a “Y” shape, and when scientists explain how a vaccine works, they’re usually referring to the top part of the “Y” — the portion that attaches to the spike protein of a virus, preventing it from entering cells.
But the bottom part of the “Y” serves a purpose, too: if a virus has already found its way into a cell, antibodies can essentially wave a flag that signals the infection. Those flags tell the immune system to kill infected cells and which cells are infected.
Chen explained that when scientists produce synthetic antibodies, they usually leave out the effector function because it can create unwanted effects, such as causing the synthetic antibodies to accidentally flag more of the virus into cells.
And since Evusheld is currently only considered a preventive treatment for the immunocompromised, it doesn’t need to have the effector function, which only kicks into gear after the virus has gotten into cells.
But that also means the immune response Evusheld induces is less robust than that of vaccines, and it’s not as good at clearing the virus out of infected cells as a vaccine is in a person with a typical immune system.
“There will be immunocompromised people that are infected, and they need treatment as well,” said Chen, noting that the term “immunocompromised” describes a wide range of people with different conditions, some of whom would benefit from the effector function. “In that particular case, my innovation will become important.”
'I don't think it's a panacea or hallelujah moment'
According to the federal therapeutics locator maintained by the U.S. Department of Health and Human Services, as of Monday there had been 303,408 courses or doses (one course or dose equals two injections) of Evusheld allotted nationwide, 10,560 of them in Arizona.
As of Feb. 14 the U.S. government had locked in the purchase a total of 1.7 million doses of Evusheld, according to AstraZeneca. Yet an estimated 7 million people across the U.S., or nearly 3% of the population, are immunocompromised, according to the Centers for Disease Control and Prevention.
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Using that percentage calculation, about 210,000 to 220,000 Arizonans are immunocompromised and many, like Joy Hoeffler, have been avoiding public outings and socializing for much of the pandemic. Hoeffler was a paralegal before her diagnosis of pemphigus vulgaris left her unable to work.
"I've been extremely isolated. There was a brief time when the vaccines came out before I was on very much medication that I felt safe to try to go out a little bit," said Hoeffler, who has received four doses of COVID-19 vaccine, per the CDC recommendation for people with compromised immune systems.
"But then I had to get on additional medications that suppressed my immune system more and obviously went back to isolating. It's been a very long and lonely couple of years."
Dr, Mark Ballow, a professor of pediatrics in the division of allergy and immunology at the University of South Florida, said having Evusheld available is promising, although not everyone with a compromised immune system has been able to get it.
Where Ballow lives, hospitals and clinics are giving priority to patients who have received organ transplants and those who are getting chemotherapy, which so far has left out a lot of patients who are immune deficient or who have suppressed immune systems, he said.
"It may allow them to almost normalize their life," he said of patients who receive Evusheld. "I still would not like to see patients who are immune-suppressed or patients who have immune deficiency compromise themselves in a situation where there's a large gathering and people are not cautious."
Kids under the age of 12 are not yet qualified to receive Evusheld, but there are kids in that age group who could benefit from it. Ballow, who is also consulting medical director for the national Immune Deficiency Foundation, said studies are underway to expand the age of those eligible for Evusheld to include younger children, though that process could take more than a year.
Ballow tells patients with immune deficiencies that they need to get vaccinated, and get booster doses, too, even if they get Evusheld injections.
"This is not a substitution for vaccination. Because clearly we have demonstrated, at least in patients with primary immune deficiency, that many of them can respond, even partially, to the COVID vaccine," he said.
Officials with the national Leukemia & Lymphoma Society say they are hearing from patients who are eager to get Evusheld but not able to access it for various reasons, including varied qualifying standards at health care facilities, likely because of low supply.
"There is a demand and a shortage and it's hard for people to get it. Initially like they did with other things, the federal government is distributing it to states based on population and the states distribute it to local hospitals," said California family physician Dr. Larry Saltzman, who is executive research director at the national Leukemia & Lymphoma Society and also a leukemia patient.
"There are gradations of who is at risk. That means there are hospitals and health centers that don't have access to this. Each hospital, they are locally creating what I'll call priority lists. ... They rank people by who should be put to the front of the line to get it."
Saltzman received his two injections of Evusheld about two weeks ago. Where he lives, hospitals and medical centers that do bone marrow transplants are the facilities that received the first supply.
"People who are on treatments for cancer or MS or things like that, because of the treatments, it negates the body's ability to create its own defenses," Saltzman said. "When I got the vaccine, I didn't make any antibodies."
A recent study of 1,400 patients by the Leukemia & Lymphoma Society published July 21 in the journal Cancer Cell found that about one in four blood cancer patients failed to produce detectable antibodies after COVID-19 vaccination.
Saltzman said he knows Evusheld works because of the high antibody levels in individuals who have received it.
A primary analysis from a randomized, double-blind, placebo-controlled clinical trial showed 3,441 Evusheld recipients saw a 77% reduced risk of developing COVID-19 compared to the 1,731 individuals who received a placebo, which is a statistically significant difference, according to FDA officials.
In additional analyses, the reduction in risk of developing COVID-19 was maintained for Evusheld recipients through six months, the FDA says.
Still, knowing that he's got the added protection of Evusheld has not led Saltzman to rush out and change his behavior, which has been extremely cautious throughout the pandemic. He doesn't eat indoors at restaurants, or go to shows or movies. He would not even think about flying to New York City to see a Broadway play, for example.
"I don't think it's a panacea or a hallelujah moment," said Saltzman, who had already received four doses of the COVID-19 vaccine when he got his Evusheld injections. "They call it a preventative monoclonal but quite frankly it doesn't prevent anybody from coming in contact with COVID."
Reach health care reporter Stephanie Innes at Stephanie.Innes@gannett.com or at 602-444-8369. Follow her on Twitter @stephanieinnes.
Melina Walling is a bioscience reporter who covers COVID-19, health, technology, agriculture and the environment. You can contact her via email at mwalling@gannett.com, or on Twitter @MelinaWalling.
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