Developing Antiviral Treatments

 

Vaccines are not enough. We are blessed with three current Covid-19 vaccines, from Pfizer, Moderna and now Johnson & Johnson, with another to come from Novavax. But antiviral treatments will still be needed for those who contract the disease.

Vaccines will make the largest contributions to controlling this pandemic, but many people will still need treatment. That’s where new antiviral therapies come in. We have already heard of Gilead’s antiviral remdesivir and monoclonal antibodies developed by Regeneron Pharmaceuticals and Eli Lilly. These two treatments are making significant contributions today to treating those already infected with Covid-19.

But that is not enough. Allysia Finley, writing in The Wall Street Journal, reminds us that mutations in the virus are happening and more therapy tools are needed. These mutations, or variants, can deform the sites to which antibodies bind before they neutralize the virus. This means a constant battle to stay one step ahead of the virus.

Gilead says remdesivir appears effective against the new strains. It is the only FDA-approved antiviral for Covid-19, and the five-day infusion treatment is limited to hospital patients. Since antivirals are most effective early in an illness, developing outpatient treatments is essential to limiting the number of hospital admissions and increasing their effectiveness.

There are several different means to antiviral treatment. Remdesivir prevents the virus from duplicating its genetic code, like creating a paper jam in a copier machine. Scientists at the University of Texas last month published a study in the journal Molecular Cell in which they identified the key mechanism remdesivir uses to inhibit the virus’s replication. That could lead to the creation of more potent and perhaps ingestible drugs.

Oral medication you could take at home would be an important step forward. There is reason for some optimism this might happen. Merck is testing a oral compound, molnupiravir, that works by creating errors in the virus’ copying code. One advantage to that approach is that viruses don’t appear to develop resistance. Merck hopes to share early efficacy results from a late-stage trial by April.

The antidepressant fluvoxamine is also showing promise as an antiviral and anti-inflammatory drug. The Journal of the American Medical Association published a small randomized control trial which found that not one patient who received fluvoxamine within seven days of symptoms experienced clinical deterioration versus 8.3% of those who did in the placebo group. In another small, but non-randomized trial of infected horse racetrack workers in California found that none who took the drug got sicker, versus 12.5% who didn’t were hospitalized. These are encouraging early studies.

Another promising new drug is plitidepsin, which is derived from sea squirts and used to treat multiple myeloma in Europe and Australia. Scientists at UC-San Francisco found that it was 27.5 times as potent as remdesivir against the coronavirus in the lab. The drug is now being tested on a few dozen patients in Spain, and its manufacturer, PharmaMar, says it is seeking regulatory approval to launch larger trials.

Plitidepsin holds great promise also because it targets human proteins the virus needs to replicate, which means it could work against any new variants that might arise in the future. “If you’re targeting a human protein, it doesn’t matter how much the virus mutates,” said study co-author Nevan Krogan in an interview. “We’re hoping this gets approved quickly and it can be used in this world war fight against this virus.”

There is also work being done to develop drugs that can act as immune modulators, tamping down the overreactive immune response to the virus that often leads to major complications such as pneumonia. Merck has developed a novel immune modulator, which seems to reduce the risk of death or respiratory failure by 50% in hospitalized patients with moderate to severe illness. NIH is also testing investigational drugs provided by several pharmaceutical manufacturers that target different immune-system pathways, though the trial isn’t expected to be completed until later this year.

Operation Warp Speed instituted by the Trump administration helped advance approval of new therapies by coordinating more large randomized trials with drug makers and healthcare systems. The Biden administration needs to continue these cooperative arrangements to facilitate promising new therapies. This could hasten FDA approval of these new drugs. It is hoped that the acceleration of the usually laborious process of FDA approval will continue to make these new therapies available to the general public as soon as they show evidence of efficacy and safety.

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