Back in December, the big worry about two newly approved treatments for early COVID-19 was that demand would far outstrip supply.
After all, some famous men had taken monoclonal antibodies after they were infected in the fall — some of them before the drugs received emergency-use authorization — and became highly visible converts.
Former President Donald Trump called a drug made by Regeneron a “cure.” (He was also given other treatments that may have helped him recover.) Ben Carson, former secretary of Housing and Urban Development, was convinced the Regeneron combo of two antibodies saved his life. Former New Jersey Gov. Chris Christie announced that he got a drug made by Eli Lilly & Co. Trump’s personal attorney Rudy Giuliani said he felt better immediately after an infusion of the Regeneron cocktail.
Now, a different problem has emerged. While more than 640,000 doses of the drugs had been shipped to hospitals and a few other providers by Jan. 6, only about a quarter have been used, according to the Department of Health and Human Services. Even as record numbers of Americans contracted the virus, supply of these drugs — the only treatments available for high-risk, newly diagnosed people who do not yet need hospitalization — has, in fact, far outstripped demand.
“It’s just being way underutilized everywhere,” said Gerard Criner, chair of thoracic medicine and surgery and director of the Temple Lung Center.
HHS and the Department of Defense have purchased 4.5 million treatment courses from Regeneron and Eli Lilly. The drugs are free to patients, who must be 65 and older or have medical conditions such as obesity or kidney disease that put them at risk for severe coronavirus.
As with vaccines, logistics are an issue
The reasons that area doctors gave for unexpectedly low use of monoclonal antibodies — poor federal planning for the logistics of giving the drugs, a reliance on hospital workers already pushed to the limit by caring for COVID-19 patients and giving colleagues vaccines, inadequate information for patients and primary-care doctors — sound familiar to anyone who’s been following the troubled vaccine rollout.
Criner doesn’t think the government bought too much of the drugs. “I think there’s been no thought process in any detail about how to get these to patients,” he said. Overburdened hospitals, he added, are “probably the last place” that should be asked to do more now.
Both treatments, which have long, tongue-twisting names we will use only once here, received emergency authorization from the Food and Drug Administration in November. The Regeneron cocktail is a combination of casirivimab and imdevimab. The Lilly drug is bamlanivimab.
When a virus invades our bodies, antibodies are our natural first line of defense. Because most people have not previously been exposed to the new coronavirus, it can take a while to ramp up antibody production. This can be particularly true of older and less healthy people with impaired immune systems. Monoclonal antibodies, which are made in laboratories, are a way to boost the natural response and potentially fight off the virus before it does serious damage.
According to phase 2 clinical trial data, 3% of high-risk patients treated with the Lilly drug needed hospitalization or emergency-room visits compared with 10% who got a placebo. The FDA said that 3% of similarly high-risk patients needed hospitalization or ER visits after treatment with the Regeneron cocktail compared with 9% of the placebo group.
A National Institutes of Health treatment guidelines panel decided there was insufficient evidence to recommend for or against the Lilly antibody. The Infectious Diseases Society of America concluded it was not for routine use but was a “reasonable treatment option” when a patient puts “high value on the uncertain benefits and a low value on uncertain adverse events.” People who get the drugs can have allergic reactions. Some have also reported nausea and other symptoms.
Some doctors, though, said the treatments are worth trying at a time when so many are dying. “We think it’s a promising drug,” said Ryan Bariola, an infectious-diseases doctor at University of Pittsburgh Medical Center (UPMC).
Racing to meet a short deadline
While monoclonal antibodies are used to treat cancer and autoimmune disorders, they’re new for infectious disease, and they come with new challenges. For one thing, they’re not given as a shot or a pill. They require an hour of intravenous treatment followed by an hour of observation. You can’t exactly welcome people with active COVID-19 into infusion suites that cater to patients with compromised immune systems. This means hospitals, which have so far gotten most doses, have had to set up special treatment areas or relegate COVID-19 treatment to hours when uninfected patients won’t be around.
The drugs also need to be given early, ideally very soon after a patient tests positive. Anyone who needs hospitalization or extra oxygen is disqualified. So, someone who waits to get a test until they have symptoms and then waits several days for results may miss the window. And, of course, some people don’t bother with tests at all until they’re too sick.
Plus, doctors and patients need to know the drugs exist, so that they can suggest the treatment. “Everybody has the mind-set that there are no treatments. That also includes physicians,” said Martin Topiel, chair of infectious disease for Virtua Health. “We really haven’t changed the culture and the mind-set on that.”
After Kathy Lefczik, a 62-year-old Maple Shade woman, tested positive on Jan. 15, her Virtua doctor suggested that she get monoclonal antibody treatment. She has diabetes and high blood pressure, risk factors that made her eligible for the drug. She had eaten with a friend — inside without a mask — the previous Saturday. The next day, the friend, who is older and has chronic lung problems, had symptoms. The day after that, Lefczik had a headache, cough, runny nose, fatigue, and muscle aches. “Because of my underlying problems, I was very afraid,” she said.
On Jan. 17, before her infusion of the Lilly drug at Virtua Willingboro Hospital, Lefczik learned that her friend had been hospitalized. Lefczik whiled away the infusion and observation time by playing games on her phone. “The next day, on Monday, I woke up, and I felt like a whole new person,” she said. By Tuesday, she had a lingering cough and some stuffiness, but the fatigue was gone. “I honestly feel fine,” she said.
It all seemed simple to her, but area doctors said keeping everyone safe is not easy.
Because of the logistical challenges, it took Temple five weeks to create a monoclonal antibody infusion area for COVID-19 patients in its COVID-19 building, Criner said. It can handle 12 patients a day but is so far infusing only two or three. Penn Medicine created a dedicated infusion center that could treat 16 coronavirus patients a day. It has treated up to 10, for a total of 70, said Pablo Tebas, an infectious-diseases doctor. Virtua could treat 20 patients a day in Willingboro. On a good day, it treats 10, Topiel said. Virtua is also giving the drug at emergency departments and managed to give 240 doses in six weeks. Topiel thinks the system could treat three times as many people if everyone who is eligible got it.
In Western Pennsylvania, UPMC, which has received about 2,000 doses, now has 15 infusion centers able to give the drugs. It has given 350 to 400 doses, including about 30 in UPMC nursing homes, Bariola said.
Some hospitals also have clinical trials available for people who don’t qualify under the emergency authorization.
To speed use, the federal government has set up three infusion centers of its own in hard-hit Arizona, California, and Nevada. It also created an online treatment locator for patients.
One promising approach is an HHS-supported program at Penn that uses home infusion nurses to give monoclonal antibodies to infected nursing home patients. The drug is perfect for long-term care residents, said Nina O’Connor, chief of palliative care at Penn Medicine, who is running the pilot. They are tested frequently, so infections are identified quickly. Because of age and other infirmities, most residents qualify for the treatment.
While nursing homes can give intravenous medicines, Penn decided to use outsiders because facility staff already are stretched too thin. “Providing the staff to do the infusion makes a big difference,” O’Connor said.
So far, Penn Home Infusion Therapy has treated residents of 29 long-term care facilities in the region.
Damian Dodge, project manager for the home infusion therapy team, said it can be tough to finish all the paperwork within the short time window, especially if a family member has to be involved because a patient has dementia or if a facility has a large outbreak. His team did 25 infusions in one day at one facility. The pilot has used 275 of its 500 doses.
The most important question is how well the drugs work. Doctors said it’s too soon to tell. They can say that patients are having very few problems with the infusions, and there’s anecdotal evidence that patients are benefiting.
“I’ve seen people get better in 24 hours,” Tebas said.
Topiel said none of Virtua’s treated patients have been hospitalized. He thinks it’s important to offer average patients the same treatments as prominent politicians got.
“Like many of these therapies to treat COVID, we need more data and more information,” he said. “... On the other hand, this is the only thing we have in the armamentarium for outpatients.”