The COVID-19 pandemic rages on, in spite of pronouncements to the contrary by President Biden and some media armchair experts. Total hospitalizations in the U.S. are currently around 30,000, with deaths about 400 per day. (The number of cases is unreliable because testing has decreased and, anyway, so many positives go unreported.) Thus, we still need treatments, especially for the immunocompromised, in whom vaccines are not very effective.
Only one drug, remdesivir (brand name, Veklury), has achieved full FDA approval, but its use is limited. It is for patients who are hospitalized with COVID and are on supplemental oxygen or have a high risk of serious illness. It's taken intravenously, so cannot be administered at home.
Paradoxically, a better drug called Paxlovid, which can be taken orally, has been granted only Emergency Use Authorization, not full approval, by the FDA. Paxlovid is quite effective, as shown most recently in a study published on February 13. It found that the drug “was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports [its] use to treat patients with mild COVID-19 who are at risk for severe disease.”
However, Paxlovid 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 therapeutic candidate -- 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 February 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 percent 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 percent lower risk. Vaccinated patients who were treated with PEG-lambda in the study experienced a 51% reduction in hospitalizations relative to placebo. In unvaccinated patients treated within the first three days of symptom onset, there was an 89% reduction compared to placebo.
To summarize, both of the primary endpoints of the trial -- COVID-related hospitalizations and Emergency Department stays of longer than six hours -- were lower in the interferon recipients.
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 epithelial cells in the liver, lungs, airways, and gut, not other parts of the body, and that 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 formally announced, the FDA determined that the results of the study did not warrant even Emergency Use Authorization, let alone full approval, and the regulators want additional data. As reported in the New York Times, 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. I reviewed alpha interferons, and 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, post-approval confirmatory clinical trial, when there is an unmet medical need for the drug. In the case of PEG-lambda and COVID, the need is for 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. It reminds me of a favorite cartoon of mine. Two researchers are at the lab bench and one of them, who is holding a flask containing a liquid, says to the other, “I think we've finally done it -- discovered a drug that will confer immortality. The trouble is, it will take forever to test it."
The result of the FDA's intransigence about PEG-lambda 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, MS, MD
Henry I. Miller, MS, MD, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. His research focuses on public policy toward science, technology, and medicine, encompassing a number of areas, including pharmaceutical development, genetic engineering, models for regulatory reform, precision medicine, and the emergence of new viral diseases. Dr. Miller served for fifteen years at the US Food and Drug Administration (FDA) in a number of posts, including as the founding director of the Office of Biotechnology.
