A Blog by Jonathan Low


Sep 18, 2020

Experimental Eli Lilly Drug Reported To Reduce Covid Patient Virus Levels

This could be a breakthrough in reducing the severity of the virus and of the risk of patient death similar to that of Remdesivir earlier this year. JL

Gina Kolata reports in the New York Times:

The drug is a monoclonal antibody, a manufactured copy of an antibody produced by a patient who recovered from Covid-19. A single infusion markedly reduced levels of the coronavirus in newly infected patients and lowered the chances that they would need hospitalization.1.7% of those who got the drug were hospitalized, compared with 6% of those who received a placebo, a 72% reduction in risk. It might mean that patients could be made less infectious, but the (antibodies) are difficult and expensive to manufacture.
A single infusion of an experimental drug markedly reduced levels of the coronavirus in newly infected patients and lowered the chances that they would need hospitalization, the drug’s maker announced on Wednesday.
The drug is a monoclonal antibody, a manufactured copy of an antibody produced by a patient who recovered from Covid-19, the illness caused by the coronavirus. Many scientists hope that monoclonal antibodies will prove to be powerful treatments for Covid-19, but they are difficult and expensive to manufacture, and progress has been slow.
The announcement, by Eli Lilly, was not accompanied by detailed data; independent scientists have not yet reviewed the results, nor have they been published in a peer-reviewed journal. The findings are the interim results of an ongoing trial.
More than 450 newly diagnosed patients received the monoclonal antibody or a placebo infusion. Some 1.7 percent of those who got the drug were hospitalized, compared with 6 percent of those who received a placebo — a 72 percent reduction in risk, Eli Lilly reported.
Levels of the coronavirus plummeted among participants who received the drug, and their symptoms were fewer, compared with those who got the placebo.
The treatments so far shown to help coronavirus patients — the antiviral drug remdesivir and the steroid dexamethasone — are intended only for hospitalized patients. Those with mild to moderate disease have had to wait and hope for the best.Dr. Myron Cohen, director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill, said he was impressed. The clinical trial appears to be rigorous, and the results are “really compelling.”
Other companies, too, are developing monoclonal antibodies to combat the coronavirus, he noted: “This is the opening of a door.”
Dr. Rajesh T. Gandhi, an infectious disease specialist at Massachusetts General Hospital, applauded Eli Lilly for studying people with mild to moderate disease. “That’s where more than 80 percent of patients are,” he said.
Dr. Gandhi said it was encouraging that the drug seemed to have lowered amounts of the virus in the respiratory tract, and said it might mean that patients could be made less infectious. But that would be difficult to demonstrate, requiring enormous trials, he added.
While the data so far are “tantalizing,” Dr. Gandhi said, he wanted more detail and anticipated the completion of the study, which will include more patients.
Monoclonal antibodies are used to treat diseases from cancer to arthritis to eczema. But they are expensive and extremely difficult to manufacture.
To make its monoclonal antibody, researchers at Eli Lilly gathered blood plasma from people who had survived infections with the coronavirus, retrieving and testing thousands of antibodies from the plasma to find the ones that seemed most powerful.
Next the scientists determined that antibody’s genetic sequence and inserted DNA with that sequence into hamster ovary cells, turning them into tiny antibody factories. The bacteria were grown in huge stainless steel vats under aseptic conditions in a sterile room; the bacterial soup must be constantly monitored to ensure that it has not been contaminated by other microbes.
Once the vat is teeming with bacteria and brimming with antibodies, workers remove the soup and concentrate the antibodies for use as a drug. They ship the new drug to a plant for packaging and labeling, all the while maintaining aseptic conditions and keeping the antibodies chilled.
The process takes two to four months. The high cost of the monoclonal antibody results from the conditions that must be maintained to make such large quantities safely, said Andrew Adams, who is leading Lilly’s Covid-19 development work.
The study will eventually enroll 800 patients of all ages and in all risk categories at sites across the United States. So far the research has proceeded with unusual speed.
Working feverishly, researchers at Eli Lilly needed just six months from isolating the antibody to enrolling the first patients on June 17.
“It was an all-out effort,” said Dr. Daniel Skovronsky, the company’s chief scientific officer.
Eli Lilly is also testing the drug in nursing homes to see if it prevents infections in residents and staff members.
In addition to constantly measuring the amount of the coronavirus in blood, the investigators also sought to understand whether the pathogen was mutating to avoid antibodies.
They found that the virus was changing, to some extent: 8 percent of the viruses had mutated in participants getting the drug, compared with 6 percent in those receiving the placebo. (Presumably, the virus also was trying to dodge the natural antibodies that placebo patients were making on their own.)The investigators expected that their drug might produce a reduction in the amount of virus in patients’ nasal passages. They did not anticipate a sharp reduction in patients who needed hospitalization.
“This is the first time we have ever seen anything of this magnitude,” Dr. Skovronsky said.
The antibody drug did not produce significant side effects, he said. Patients received a single infusion, providing antibodies that should last about a month.
There is good news regarding a vaccine in these findings. If monoclonal antibodies had not worked, then the finding may have cast doubt on the notion that the virus could be stopped with antibodies.
On the other hand, the results — if they are proven accurate — do not guarantee that a vaccine will work. Eli Lilly’s monoclonal antibody is a temporary treatment; a vaccine is designed to elicit long-lasting natural antibodies and thus immunity.
Like other companies, Eli Lilly has been manufacturing large quantities of its drug — 100,000 doses — in the hope that it turns out to be effective.
The company will be discussing its data with the Food and Drug Administration, Dr. Skovronsky said, along with the possibility of obtaining an emergency use authorization allowing Eli Lilly to market the drug.
If the findings hold up, there will be comfort for the public in knowing there is something doctors can do to head off dire illness, Dr. Cohen said.
“For my wife and I, who are older and fatter — we are waiting for drugs like this so we can see our grandchildren,” he added.


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