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• Posted February 9, 2023

New Injected Drug May Prevent Severe COVID

A single injection of an experimental biologic drug may cut in half your risk of hospitalization from COVID-19 infection, new clinical trial results show.

Pegylated lambda interferon (PEG-lambda) proved effective against all COVID-19 variants encountered in this international study, including Omicron, according to findings reported Feb. 9 in the New England Journal of Medicine.

"During the study, multiple waves of variants worked through the populations in Brazil and Canada, and lambda showed efficacy against all of them,"said senior researcher Dr. Jeffrey Glenn. He is a professor of medicine, microbiology and immunology with the Stanford University School of Medicine, in California.

And the earlier patients received PEG-lambda, the better they fared, the researchers found.

Unvaccinated patients who received the drug within the first three days of symptom onset had an 89% reduced risk of hospitalization, compared to placebo, the results showed.

The results are "very exciting, because we need as many treatment modalities as we can,"said Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases.

PEG-lambda is a synthetic version of lambda interferon, a naturally occurring protein secreted by cells that sense they've been invaded by a virus.

The protein interferes with the virus' ability to replicate within cells, inhibiting the germ's spread. It also signals to neighboring cells that a virus has invaded the body, prompting a chain-reaction immune response.

"It's a natural, broad spectrum antiviral. It's the body's first line of defense against viruses,"said Glenn, who is on the board of directors and holds an equity stake in the company investigating PEG-lambda, Eiger Biopharmaceuticals.

Research into PEG-lambda has mainly focused on treatment of viral hepatitis, but early in the pandemic Glenn and his colleagues found that it was potent against lab samples of COVID-19.

That prompted this clinical trial, which involved nearly 2,000 newly infected COVID-19 patients treated at 12 sites in Brazil and five sites in Canada between June 2021 and February 2022.

Within seven days of symptom onset, patients were randomly assigned to receive either a single injection of PEG-lambda or a placebo.

Less than 3% of patients who received PEG-lambda were hospitalized, compared with nearly 6% of those who got a placebo injection. That represents a 51% reduced risk of hospitalization for those getting the drug.

The results were even better when patients got the drug within three days -- 1.9% of PEG-lambda patients wound up in the hospital compared with 3.1% of the placebo group, a relative risk reduction of 58%.

PEG-lambda also appears to be safe for patients, Glenn added.

"They couldn't tell who was on the drug and who was on placebo,"Glenn said. "The side effects were the same."

Safety is a concern when testing interferon drugs, because they are known to create a dangerous or even deadly "cytokine storm"of inflammation in the body, Glenn said.

For example, a closely related substance called alfa-interferon is used to treat hepatitis C and cancer, but it has proven toxic to numerous organ systems because receptors for it abound throughout the body, the researchers said in background notes.

But lamba interferon receptors are found mainly in the lining of the lung, airways, intestines and liver, Glenn said. It doesn't cause a major immune reaction in other types of tissue, including muscle tissue or immune cells.

"That's why you can get the same desired antiviral effect, but it's much better tolerated,"Glenn said. "And, of course, the fact that we give it just once makes it even easier."

If approved as a treatment against COVID, PEG-lambda will provide an option for people who can't take Paxlovid, Schaffner said.

Paxlovid contains an agent that increases drug activity, and that component opens up the possibility for dangerous drug interactions.

"There are some patients for whom Paxlovid is not indicated because there may be drug/drug interactions with other medications that they take, so this will provide another comparably effective early treatment for people who are infected,"Schaffner said.

Glenn is hopeful that PEG-lambda will be granted an emergency use authorization by the U.S. Food and Drug Administration, or at least be considered for expedited approval.

"Had this been approved and available for use at the beginning of the pandemic, we could have saved millions of lives. We still can save millions of lives, but it has to get some kind of authorization by health authorities,"Glenn said.

"My parents had COVID and I couldn't get them a shot of lambda,"he added. "Fortunately, we had Paxlovid, but I hope that situation will change."

Glenn said he's advocating for a future trial that would test PEG-lambda in any patient presenting at a hospital or medical clinic with a respiratory infection.

Such a trial could firm up the drug's effectiveness against COVID-19, and also see if it works against influenza or RSV (respiratory syncytial virus), he said.

"You know, that's your tripledemic right there,"Glenn said. "Lambda has fantastic potential for a broad spectrum of therapeutics to counter a respiratory pandemic or other respiratory diseases."

Glenn doesn't think the drug will be expensive, noting that it can be stored in regular refrigerators rather than the ultra-cold freezers needed for COVID-19 vaccines.

But Schaffner noted that PEG-lambda's effectiveness has been demonstrated at the same time that the federal government is calling an end to pandemic emergency declarations.

At some point this year, many people will be expected to pick up some or all of the cost for their COVID treatment, depending on their insurance status.

"Here we are talking about reducing the support for, among other things, the early treatment of people with COVID, and here's a new treatment that's just come along,"Schaffner said. "Will some people simply be excluded from these benefits because they lack medical insurance or have co-pays and deductibles that they cannot meet?"

More information

The U.S. Centers for Disease Control and Prevention has more about COVID-19 treatments.

SOURCES: Jeffrey Glenn, MD, PhD, professor, medicine, microbiology and immunology, Stanford University School of Medicine, Stanford, Calif.; William Schaffner, MD, medical director, National Foundation for Infectious Diseases; New England Journal of Medicine, Feb. 9, 2023