The spread of the omicron variant and growing evidence that it can break through all existing coronavirus vaccines has turned the spotlight onto the second line of defense – coronavirus medicines.
The new thrust comes as the medical community has come to realize that the virus can’t be dealt with solely through vaccination and prevention: Effective medicines for patients at risk of serious illness will be crucial.
The first shipment to Israel of tens of thousands of Paxlovid, Pfizer’s new oral medicine for the virus, is expected to arrive this week, after it was approved last week by the U.S. Food and Drug Administration, and by Israel's Health Ministry on Sunday.
The pill is meant for people age 12 and up who are at risk of serious illness due to preexisting conditions like diabetes or obesity. In clinical trials, it was almost 90 percent effective at preventing hospitalizations, serious illness and death among high-risk patients.
The drug’s approval is an important bit of good news after a long period during which the options for treating patients were extremely limited. By preventing serious illness, it should reduce the burden on the hospitals. Nevertheless, Paxlovid is akin to a life raft with limited capacity in the face of what is expected to become a mass infection.
The biggest weakness of Paxlovid and other new drugs is that they are effective only if given during a narrow window of time – a few days after symptoms appear. This creates significant logistical difficulties, since it requires a rapid response from everyone in the diagnostic and treatment chain. Israel’s healthcare system must be able to test people promptly, provide results quickly, determine which patients need the drug and then get it to them.
There’s also another challenge, namely persuading people to take a new drug, often in addition to other drugs they are taking for preexisting conditions, at a time when their symptoms are still mild, or even nonexistent, and they feel fairly good.
This was exemplified by Israel’s effort to treat high-risk patients with Regeneron, a monoclonal antibody that must be given intravenously within 72 hours of diagnosis.
The drug has proven effective at dramatically reducing the risk of serious illness and death in patients infected with the delta variant. Yet to the astonishment of many medical professionals, demand for the drug has been very low. Since health maintenance organizations began offering it to patients three months ago, 40 percent of at-risk patients (715 out of 1,834) have refused to take it.
When these problems are coupled with a fast-spreading pandemic, hopes that drugs will act as a powerful tool capable of compensating for the vaccines’ weakness may well prove overblown. Their contribution to the battle against the virus could even prove marginal.
Moreover, Regeneron has essentially been removed from the picture after two New York hospitals reported over the weekend that it isn’t effective against omicron, due to a mutation in the specific area of the virus’ protein shell that the drug attacks. A drug by the pharmaceutical company Eli Lilly that operates similarly has also been proven ineffective against omicron.
Another drug, made by GSK and Vir Biotechnology and called Vir-7831, is effective against omicron even though it’s also a monoclonal antibody, because it attacks a different part of the protein shell. But it still isn’t available in Israel.
Israel’s healthcare system is pinning its hopes on two new drugs that only just received approval – Paxlovid and a drug developed by Merck called Molnupiravir. The latter reportedly reduces hospitalizations and deaths among high-risk patients if given early in the disease’s progression. The FDA approved it for people with mild to moderate symptoms who are at risk of becoming seriously ill.
Israel has a purchasing agreement with Merck, known as MSD in Israel, so it is assured a supply of the drug. Sources in the healthcare system said an initial shipment of thousands of tablets is expected to arrive in another two weeks.
Unlike monoclonal antibodies, the new drugs don’t attack the protein shell. Instead, they disrupt the virus’ ability to replicate, each in a different way. Plaxlovid is a protease inhibitor, which means it attacks the enzyme protease, which is crucial to the replication process.
Molnupiravir is based on a small molecule whose presence in the host cell disrupts the replication process by essentially planting a typo in the replicating instructions. As a result, the new virus will be flawed and incapable of replicating itself.
Despite both drugs’ effectiveness it’s not clear that they will cause a real revolution in dealing with the pandemic.
“The new drugs are important news, but they have to come with a paradigm shift that’s critical in any antiviral treatment, including against the coronavirus –namely treatment at an early stage,” said Prof. Oren Tsimhoni, head of the infectious disease department at Kaplan Medical Center in Rehovot and a member of the government’s expert advisory panel on the virus. All the studies have shown that treatment “in the very first days after infection” is essential, he said.
Dr. Yasmin Maor, head of the infectious disease department at Wolfson Medical Center in Holon and another member of the panel, added, “What makes using these drugs very difficult is that they’re based on very early treatment and the window of opportunity is very short. Even Pfizer’s new drug has to be given within five days of when symptoms appear, and three days is much better.”
Prof. Dana Wolf, head of the clinical virology department at Hadassah Hospital, Ein Karem in Jerusalem, said this was true of all viral diseases, “and especially respiratory diseases. The earlier the treatment is, the better.”
“Consequently, I don’t think these drugs have the power to stop the pandemic,” she warned. “They could reduce hospitalization rates, complications, deterioration and death among patients in risk groups. But this is not a substitute for vaccination in any way.”
In light of patients’ reluctance to take Regeneron, medical professionals see a benefit in that the new drugs can be taken orally rather than intravenously or through an injection. But Maor said a campaign to educate the public would also be critical.
“The patients who refused to take Regeneron refused because they felt fine,” she explained. “But a week later, when their condition deteriorated, the drug was no longer relevant.”
And even if patients agree to take the drugs, challenges remain. Because these medications have only received emergency approval, patients will have to sign a consent form to take them and will also need follow-up monitoring.
In addition, the drugs have to be taken many times a day. Treatment with Molnupiravir, for instance, involves taking eight pills a day for five days. Treatment with Plaxovid requires six pills a day for five days.
People in high-risk groups, like the elderly or those with preexisting conditions, usually already take a large number of medications, and they are likely to be fearful about adding a new drug to the list that could disrupt their treatment regimen.
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“Plaxovid is more effective at treating the virus, about 90 percent,” Maor noted. “But it also has a lot of interactions with other drugs.”
Moreover, she said, “We still don’t know if we can give it to pregnant women. And even if the drugs are marvelous, we won’t be able to give them to everyone. Therefore, the wider a variety we have, the more the drugs will be able to complement each other.”
If the window of opportunity for drug treatment is missed, it increases the risk of serious illness and hospitalization. And once that point is reached, experts said, there’s no way to turn back the clock and prevent it. Instead, the emphasis shifts to trying to treat the symptoms.
“The moment the drugs become irrelevant and the patient’s condition deteriorates and he’s hospitalized in moderate condition, the medicinal tools become much more limited and treatment with antiviral medications is generally less effective,” Wolf said. “We’re left with steroids that regulate the uncontrolled inflammatory response and anti-clotting drugs, which work better in the later stage of the illness.”
Another antiviral drug, Remdesivir, is currently being given to hospitalized coronavirus patients with limited success. “We don’t have much to offer hospitalized patients,” Maor acknowledged. “Only steroids, anti-clotting drugs and Remdesivir, which helps a little bit.”