Scientists who’ve been reluctant to talk up any new Covid-19 treatment are suddenly using the expression “game changer” to describe the Pfizer antiviral pill Paxlovid. But the changed game will include rationing.
It’s no coincidence that it works the same way as the drugs that changed everything with the AIDS epidemic. Called protease inhibitors, they turned HIV from a death sentence to a manageable disease.
Doctors who treat Covid-19 patients are excited that Paxlovid won emergency use approval earlier this month, but ramping up supplies amid the current massive pandemic wave could unleash a rancorous ethical conflict over who should be given priority. Among those whose lives might be saved include people who are vaccinated and boosted but immune compromised, as well as people who are willfully unvaccinated. If people were mad about unvaccinated patients burdening medical staffs and taking up beds in hospitals, wait for the clamor over who gets the new pill.
In clinical trials, Paxlovid reduced risk of hospitalization by 89% when people with several risk factors were given the drug within five days of the onset of symptoms. Because it’s a pill, it doesn’t require a medical facility the way monoclonal antibodies do, and new evidence shows most of those antibody treatments won’t work against omicron in any case.
“I think it’s a game changer,” said Roger Seheult, a critical care doctor and pulmonologist in California, who talked to me this week right after finishing a shift in the ICU. But he’s wondering how the several hundred thousand doses promised by the US government will stand up to the rising wave of disease. Noting that 200,000 people are getting the virus every day, he said, “We might see a million a day once this thing hits full bore.”
He brought up Colin Powell as someone who might have been saved by Paxlovid. Powell, who died from Covid-19 last fall, had suffered from multiple myeloma — a disease that interferes with the body’s ability to make antibodies in response to infection or vaccines.
But millions of people are either immune compromised or have skipped the vaccine. Seheult said that in his hospital’s ICU, he’s also seeing a number of people with multiple health risks who have skipped the strongly recommended booster shots.
The supply problem won’t be easy to fix, said Derek Lowe, a medicinal chemist and author of Science magazine’s pharma blog In the Pipeline. The starting materials are the problem, he said. Making this kind of complex drug requires multiple steps, each one requiring different materials. “And each of those things has to be sourced — how much of it can they make really fast, and make it with sufficient purity and get it delivered,” Lowe said, adding, “You've got five, 10, a dozen, 20 different chemicals you have to worry about in the same way.”
The process often involves multiple countries. “Eventually, we're depending on other countries that still have a big, ugly, dirty, smelly fine-chemical industry,” he said.
Merck has also come up with an antiviral pill, molnupiravir, which had initially shown similarly promising results but now looks to be only around 30% effective in preventing hospitalization. The Merck drug also raised concerns that its ability to cause mutations in the virus could become a “breeding ground” for new variants.
Seheult and other doctors still see it as a backup. Paxlovid can potentially interfere with other drugs, so it might not work for patients who can’t take a break from their normal drugs for even a few days.
Paxlovid is basically two drugs. One is the actual protease inhibitor, which works by stopping a key enzyme needed for the virus to reproduce itself. Such a direct attack should work even on those with non-functional immune systems.
The other part, ritonavir, is an older HIV drug, which increases the effective dose of the antiviral part by slowing down the liver’s ability to metabolize and destroy it. That’s why it might have the unwanted side effect of causing other drugs to build up into toxic doses.
The two drugs that make up Paxlovid are similar to drugs given to HIV patients for life, but for Covid-19 the course of medication would only take five days. No safety concerns came up in the clinical trials. The need to give it within five days is a limitation, but people who know they’re at high risk could, in theory, be prepared with at-home Covid-19 tests — provided the supply of those can ramp up fast enough.
Just as HIV drugs changed the way society viewed relationships and made life for many single people less stressful, so the presence of an effective Covid drug could ease the emotional and social toll of the pandemic. The vaccines went a long way in that direction but left behind people who can’t get the full benefit because they have suppressed immune systems due to age, diseases or the need to take immune-suppressive drugs.
Should they have to compete with people who are also at risk through their choice to skip vaccines? About half of unvaccinated people say they would refuse Paxlovid, according to a recent Harris poll, but that leaves a lot of potential demand in the other half — and many others might change their minds if they thought their lives were in immediate danger.
Then there’s a whole gray zone of people who haven’t gotten around to getting boosted, despite being over 65 or having conditions such as obesity and diabetes. Only about a quarter of US adults have gotten the booster, so this group may make up the bulk of demand for Paxlovid.
It’s always possible that things won’t go as expected. Doctors thought they’d have to ration ventilators, but they learned that many patients did better with supplemental oxygen. This time around, nobody knows yet how big a hospital surge the omicron cases will cause.
Even when the supply ramps up, Lowe and other experts worry that if the drug is used too widely, it might conceivably increase the chance that the virus would develop resistance. So the medical community will have to exercise judgment in prescribing this drug for the foreseeable future. The rest of us should temper hopes for an easy cure, and get that booster shot.
Bloomberg
