Eli Lilly and : Highly Touted Monoclonal Antibody Therapies Sit Unused in Hospitals

By Sarah Toy, Joseph Walker and Melanie Evans

Doses of monoclonal antibodies -- Covid-19 therapies authorized for emergency use last month -- are sitting unused in hospital pharmacies, even as cases surge across the country.

Hospitals say the rollout of the therapies has been stunted by a lukewarm response from infectious-disease specialists, who say they want more clinical trial data before using them on a regular basis. Medical centers are also grappling with a lack of awareness and interest from both the primary-care doctors who would normally prescribe the drug and patients who are offered it. And some places are dealing with a shortage of space and staff to administer the therapies.

When monoclonal antibody therapies from Eli Lilly & Co. and Regeneron Pharmaceuticals Inc. were approved for emergency use in November, health agencies were worried there wouldn't be enough supply to meet demand. Now, health-care providers are administering just 20% of the doses they receive each week, according to officials with Operation Warp Speed, the federal initiative to support development of new drugs, vaccines and diagnostics for Covid-19.

Monoclonal antibodies, which are also used to treat other diseases, work by taking a page from the body's own natural antibody defenses, targeting specific spots on intruding pathogens. Eli Lilly's bamlanivimab and Regeneron's casirivimab and imdevimab cocktail target the SARS-CoV-2 spike protein and are injected intravenously. Early trial data of the therapies found they could reduce hospitalization or emergency visits among high-risk patients.

"Physicians are not ordering the drug," said Michael Ison, an infectious-disease physician at Northwestern Memorial Hospital who is helping lead the monoclonal-antibody rollout there and in the wider Northwestern Medicine health system, which includes 10 hospitals across the Chicago area and northern Illinois.

Demand from doctors in the Northwestern system has been relatively low and many patients aren't all that interested, he said. Although several hospitals have set up spaces for the infusions and have made arrangements for staff to deliver them, some physicians just aren't comfortable with prescribing the therapy because it is so new and it is hard to discern which patients will benefit from it, Dr. Ison said.

The monoclonal antibody treatments from Eli Lilly and Regeneron were approved by the U.S. Food and Drug Administration for use in patients with mild or moderate Covid-19 who are at high risk of progressing to severe symptoms or hospitalization. The FDA has a specific definition of what high risk means, which includes people who are 65 years of age or older, or people who are considered obese, with a body-mass index of 35 or more. The therapies are supposed to be administered as soon as possible after a patient receives a positive test result, within 10 days of the onset of symptoms.

But sussing out who would benefit and when isn't easy, doctors say. And patients sometimes recover on their own within a couple of days, which renders the therapy moot. Often, patients with mild symptoms refuse the therapy after being offered it, doctors say.

"A significant number of patients have declined it," said Emily Rubin, a pulmonary and critical-care physician who has been helping lead the monoclonal antibody rollout at Massachusetts General Hospital in Boston.

MGH has received about 275 doses of Eli Lilly's bamlanivimab, but only 10% of that has been administered so far, she said. The hospital also received a small supply of Regeneron's product, but that hasn't been used at all, she said.

Some patients who meet the high-risk criteria have mild or moderate symptoms that are improving, so they aren't interested in coming in for an infusion, Dr. Rubin noted. Others aren't able to spare the two hours required for administration and monitoring. Still others are told of the benefits of the drug according to trial data and decide the benefit is too dubious.

A recently published interim analysis of Regeneron's cocktail found that it could reduce viral load in some patients, and an interim analysis of bamlanivimab found that five out of 309 patients who received the therapy required a visit to the emergency department or hospitalization, compared with nine out of 143 of the placebo population.

But some infectious-disease physicians aren't convinced, saying more data are needed.

"To be really certain about the results, you need greater numbers," said Rajesh Gandhi, an infectious-disease physician at MGH and a member of the Covid-19 treatment guidelines panels at the National Institutes of Health and the Infectious Diseases Society of America.

The NIH has said there are insufficient data to recommend for or against the use of the Eli Lilly and Regeneron treatments. Neither should be considered the standard of care for treatment of patients with Covid-19, NIH said. The IDSA also recommends against the routine use of bamlanivimab.

The need for more data doesn't mean people shouldn't be treated now, said Rich O'Neal, Regeneron's vice president of market access. "It's going to be really challenging if we continue to wait too long for information and data to continue to decrease the impact of the crisis."

"The emergency-use authorization is based on a standard of data which is different than the normal drug approval. We fully acknowledge that," said Daniel Skovronsky, Eli Lilly's chief scientific officer. "On the other hand, we're excited about the potential that we've seen in our clinical trials: particularly, we saw reduced hospitalizations and emergency-room visits. Although it was a small trial, Regeneron had almost the exact same kind of impact -- a different molecule but the same mechanism."

UW Medicine, which has four hospitals, largely isn't using the monoclonal antibody therapies, said Shireesha Dhanireddy, an infectious-disease doctor at the Seattle-based system.

Although the hospital system has made a few, limited requests for some of Washington state's supply of Eli Lilly's monoclonal antibody drug bamlanivimab, UW Medicine isn't routinely using it, she said, after deciding the benefits were too uncertain and administering the drugs would add additional strain on health-care workers.

Administering bamlanivimab is time-intensive, she said, and staff have been urgently needed to care for rising numbers of Covid-19 patients.

UW Medicine in late November and early December also needed staff to complete plans to vaccinate its employees for the novel coronavirus, an effort that is now under way, Dr. Dhanireddy said.

In contrast, health-care system Northwell Health in New York is moving ahead with its monoclonal-antibody rollout, setting up five sites where it can administer the intravenous drugs. Some are located in tents that were used as overflow units during the Covid-19 surge in New York City in the spring, said Warren Licht, vice president of ambulatory operations at Northwell who has been leading the effort. One is located in the emergency room of Northwell's Cohen Children's Medical Center, he said.

He said Northwell hopes to open more sites and is planning for more emergency-room locations. He is also hoping to include Northwell's skilled-nursing facilities in the rollout and to set up a program for home infusions.

States are beginning to expand the availability of infusions outside of the hospital, including in nursing homes and outpatient infusion clinics, and offering to administer the drugs in patients' homes, said Janet Woodcock, head of drug evaluation and research at the FDA who is on leave to work with Operation Warp Speed.

In the future, doctors' offices could also start offering to provide the treatment, which may be particularly helpful in rural areas where there aren't many nearby health facilities, she said.

Write to Sarah Toy at [e-mail], Joseph Walker at [e-mail] and Melanie Evans at [e-mail]

(END) Dow Jones Newswires

12-27-20 1157ET