- The first oral antiviral treatment available for people with COVID-19 has just received approval for use by the UK government.
- Many drug companies have other drug candidates in development with the hope that they might help reduce hospitalizations and transmission.
- Pfizer published an article demonstrating that its drug candidate is safe and has antiviral effects on SARS-CoV-2.
Although scientists have developed vaccines to help protect people against COVID-19 in record time during the pandemic, the development of an antiviral that targets SARS-CoV-2 – which is the virus that causes COVID -19 – turned out to be more complex.
Many antivirals are in development. Ridgeback Biotherapeutics and Merck Sharp & Dohme Just Received Approval For Their Oral Antiviral Molnupiravir For Use In COVID-19 Patients In The UK
The decision came following the results of a phase 3 clinical trial that demonstrated a 50% reduction in the risk of death or hospitalization compared to placebo. Merck is closely followed by Roche / Atea and Pfizer, which have their own drug candidates in Phase 2 and 3 trials.
Some jurisdictions have high hopes for the development of antivirals to combat hospitalization rates. In fact, the UK government recently announced that it has ordered 730,000 doses of COVID-19 antivirals.
Although most orders were for molnupiravir, a quarter of a million were for Pfizer’s drug candidate PF-07321332 and the HIV antiretroviral drug ritonavir. This despite the fact that the pharmaceutical company did not publish any clinical trial data for the candidate drug at the time.
Now Pfizer has released details of a Phase 1 clinical and preclinical trial. The results show that its drug candidate is safe for humans at concentrations effective against SARS-CoV-2 in laboratory tests. This is true both when the drug is used alone and when combined with ritonavir.
Dr. Adam Bailey, assistant professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison, explained the rationale behind this drug duo at Medical News Today.
“They are both protease inhibitors. Drug cocktails that have the same target can often be an effective way to reduce the likelihood of [resistant] mutations arise. Instead of hitting a single mutation that confers resistance to one drug, the virus must acquire two or more different mutations to generate resistance to both drugs simultaneously. “
Pfizer started his business by reviewing drugs he developed in preclinical trials during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak caused by the SARS-CoV-1 coronavirus.
The researchers found that one of the drugs they had developed for intravenous use, which is currently in separate clinical trials, was effective against SARS-CoV-2.
Pfizer then designed its oral drug candidate to inhibit a specific protease used by SARS-CoV-2 and named this new drug candidate PF-07321332.
Protease inhibitors work by preventing viral replication. Inhibition of viral replication should slow or stop the infection. By administering PF-07321332 with the existing Pfizer protease inhibitor, ritonavir, researchers expect the second drug to help slow the metabolism, or breakdown, of PF-07321332. This means that the medicine has to stay active in the body for a longer time.
In a series of experiments described in the journal Science, the researchers showed that the drug exhibited antiviral activity in the epithelial cells of the lungs and lowered the viral load in mice.
In a small trial of 18 healthy adults, researchers at Pfizer then tested the safety of 150 milligrams (mg) and 250 mg of PF-07321332 taken twice daily with and without 100 mg of ritonavir. They found the drug to be safe and well tolerated with and without ritonavir.
The company is currently conducting Phase 2 and 3 trials to determine whether or not the drug is effective in COVID-19 patients at risk for standard and severe illness. They also want to understand whether or not this prevents transmission of the disease among close contacts of people with COVID-19.
A challenge for the next phase of the trials might be to demonstrate the drug’s effectiveness against COVID-19, as symptoms often appear after peak viral replication.
This caused problems when investigating the effectiveness of remdesivir against COVID-19 in clinical trials, said Dr Bailey MNT. People are given remdesivir intravenously, while they can take Pfizer’s drug candidate by mouth. This gives hope that it could be given earlier or to people at high risk as a preventive measure.
“People often show minimal symptoms when SARS-CoV-2 reaches peak replication; the time during which antivirals would be most effective […]. This is true for most viral infections, but if given as soon as a person becomes symptomatic, or as prophylaxis after high risk exposure, they can still be effective, like oseltamivir for influenza infection. .
Despite these potential challenges, developments at Pfizer and Ridgeback Biotherapeutics and Merck Sharpe & Dohne are attractive prospects. That’s according to Professor Monica Gandhi, professor of medicine at the University of California at San Francisco (UCSF) and director of the UCSF-Gladstone Center for AIDS Research.
She said MNT: “This first oral protease inhibitor of its kind for SARS-CoV-2 is a very exciting development. COVID-19 is unlikely to be eliminated, but will become endemic, making tools for its continued control paramount. Vaccines are the mainstay of prevention, but treatment will be necessary for those who refuse vaccination or for those with moderate infections from the vaccine. “
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