New Covid antivirals pills are needed

Even as omicron infection rates plummet, preparations must be made for whatever Covid-19 throws at us next. The best-case scenario is that we live with an endemic virus that causes only mild infections in most people who are vaccinated. But the possibility remains that new variants will arise.
A good way to prepare for any eventuality is to develop new antivirals — ones that can be used more easily than the two existing Covid pills. A new wave of pills advancing into human studies this year could help build out the medicine cabinet. Pardes Biosciences, a two-year-old biotech firm that went public in December, became the latest company to unveil early data for what it hopes will be a better drug.
The antivirals already in use — Pfizer’s Paxlovid and Merck’s molnupiravir — were authorised late last year with much fanfare. Their arrival promised a world in which people newly diagnosed with Covid could be handed a pill pack that would protect them from serious illness.
In practice, though, their use is more complicated. Molnupiravir carries safety concerns in certain populations and has proved only modestly effective. It’s widely available, yet few doctors seem to be prescribing it. In a recent update on Covid-19 medicine allocations, Derek Eisnor of BARDA (the Biomedical Advanced Research and Development Authority) noted that pharmacies are becoming overstocked. European regulators, meanwhile, are skeptical of its benefits and might not approve it use.
Pfizer’s Paxlovid has its own limitations. It combines a new antiviral for Sars-CoV-2 with an older HIV medicine called ritonavir, which boosts its efficacy. The drug is very good at keeping at-risk people out of the hospital, but
ritonavir can interact with many commonly prescribed medications. So doctors and pharmacists need to be careful in handing it out, which makes it less of an easy fix for early infections than some had hoped.
Pardes’s early data suggest that its pill, dubbed PBI-0451, won’t interact with other drugs. And because it works differently from molnupiravir, it should be safer for the broader population. Like Paxlovid, the Pardes pill blocks Covid’s so-called main protease, an enzyme that snips apart viral polyproteins into functional pieces. Because this target enzyme doesn’t resemble any produced by the human body, there’s little risk of dangerous side effects.
The enzyme also looks strikingly similar across various coronaviruses, so any pills developed for Covid-19 will have a decent chance of working in a future pandemic caused by any member of the coronavirus family.
The not-so-good news from the studies so far is that the Pardes pill seems less potent than the Paxlovid-ritonavir combination. But Brian Kearney, Pardes’s chief development officer, says Paxlovid-level viral suppression might not be necessary, and the company is still exploring higher doses. Pardes will publicise more data on the drug at a conference in late March.
Several other companies are racing with Pardes to create a new easy-to-use Covid antiviral. Earlier this month, Shionogi offered promising early data on its own main protease inhibitor, which it is moving into late-stage studies in Japan. This pill, called S-217622, did about as well as Paxlovid in lowering Covid patients’ viral load. But the antiviral does seem to have the potential to interact with other drugs, Jefferies analyst Dennis Ding said in a note to investors.
Japanese regulators are considering whether to authorise the Shionogi pill, and the company is looking for partners to market it globally.
Meanwhile, Enanta Pharmaceuticals’ main protease inhibitor EDP-235 is about to undergo trials, and Novartis says it is on track to put another such pill into human trials this year.

—Bloomberg