COVID-19 hospitalizations totaled around 40,000 and deaths were over 400 per day as of Feb. 10. (Case numbers are unreliable because testing has decreased and also, so many positives go unreported.) Thus, we still need treatments.
Paxlovid is quite effective, but it has a significant disadvantage: It has potentially dangerous drug-drug interactions with a long list of commonly prescribed drugs that physicians and patients are loath to discontinue during Paxlovid's five-day course. And it is not recommended for patients with severe kidney or liver disease.
Fortunately, there's a new kid on the therapeutics block: a drug called pegylated interferon lambda, or PEG-lambda, that performed well in a late-stage (Phase 3) clinical trial, the results of which were published on Feb. 9. ("Pegylated" refers to a chain of polyethylene glycol attached to the interferon molecule to lengthen its half-life in the blood.)
In a cohort of mostly vaccinated patients, 931 patients received a single subcutaneous (under the skin) injection of PEG-lambda, and 1,018 were given a placebo injection.
-- Patients who received the drug within seven days of showing symptoms were 51% less likely to be hospitalized or to need an extended visit to an emergency room compared with those given a placebo.
-- People given PEG-lambda within three days of the onset of symptoms had a 58% lower risk.
-- Vaccinated patients who were treated with PEG-lambda in the study experienced a 51% reduction in hospitalizations relative to the placebo.
-- In unvaccinated patients treated within the first three days of symptom onset, there was an 89% reduction compared with the placebo.
In summary, both components of the primary endpoints of the trial — COVID-related hospitalizations and emergency department stays of longer than six hours — were significantly lower in patients who got the drug.
Interferons are chemicals that are part of the innate immune response, the body's first line of defense against viral infections. Alpha interferons have been used for decades to treat certain cancers and viral diseases, but only sparingly because of severe side effects, including flu-like symptoms and depression. However, lambda interferon binds preferentially to receptors on cells that line the liver, lungs, airways, and gut, but not other parts of the body, which reduces side effects.
A critical finding in the study was that the patients who received the PEG-lambda experienced no more side effects than those who received a placebo. Another plus is that the drug targets a part of the virus that doesn't mutate, so it's likely to protect against and treat even new variants of SARS-CoV-2.
The news is not all good, however. For reasons that have not been made public, the Food and Drug Administration determined that the study was not adequate for Emergency Use Authorization, let alone full approval, and regulators want additional data. Executives from Eiger BioPharmaceuticals Inc., the manufacturer of the drug, intimated that "part of the problem seemed to be that the clinical trial did not include an American site, but rather only sites in Brazil and Canada, and that it was initiated and run by academic researchers, rather than the company itself."
I spent 15 years at the FDA in several positions -- as a medical reviewer, special assistant to the head of the agency, and founding director of the Office of Biotechnology. Along the way, I reviewed alpha interferons. Although I have only seen the publicly available data on PEG-lambda to treat COVID, I believe the Phase 3 study reported in the New England Journal of Medicine was of sufficiently high quality to warrant at the very least an emergency use authorization and, quite possibly, an accelerated approval. The latter is granted, subject to a subsequent confirmatory clinical trial, when there is an unmet medical need. In the case of PEG-lambda and COVID, that need is having a treatment in reserve in case the SARS-CoV-2 virus evolves to become highly resistant to the protection afforded by existing vaccines.
The decision by the FDA appears to be overly conservative, although obstructionist might be a better term. The result will be that many COVID patients who can't or won't take Paxlovid will needlessly end up in the hospital or the morgue.
Henry I. Miller, a physician and molecular biologist, is the Glenn Swogger distinguished fellow at the American Council on Science and Health. He was the founding director of the FDA's Office of Biotechnology.