After A Year Battling COVID-19, Drug Treatments Get A Mixed Report Card

Drugs to treat COVID-19 are being fast-tracked for development, but the pace can't match the astonishing speed that gave birth to the vaccines.

But one year into the pandemic, there has been strong progress toward effective drug treatments, and the groundwork has been laid for drugs to kill the virus and arrest disease.

If you want to see a scorecard on COVID-19 drugs, you can check out two good sources. Expert panels are constantly updating treatment guidelines for both the National Institutes of Health and the Infectious Diseases Society of America.

Potential drugs are sorted into three basic categories: They work, they don't work, or there simply isn't enough information to know.

"When these panels first started, essentially all the drugs were in that category that we don't have enough information," says Raj Gandhi, an infectious diseases doctor at Massachusetts General Hospital and the Harvard Medical School, who is on both of those committees. When the first guidelines came out, that ambivalent answer "was true of just about every drug that was being talked about."

As studies have produced data, the guidelines have evolved. The panels have now concluded that some drugs should be avoided, like the antimalaria drug hydroxychloroquine, which had a strong fan base. Gandhi says it's important to know what doesn't work, so people aren't subjected to needless risks from drugs that aren't going to help them.

Many other drugs remain in the we-don't-know bucket. Those include monoclonal antibodies, even though they have been granted emergency authorization to treat people with mild to moderate infections to keep them out of the hospital.

"The early data is promising," Gandhi says, "but I think the definitive trials are ongoing, and I'm looking forward to seeing those results."

Gandhi hopes doctors who see the inconclusive recommendation will steer patients toward clinical trials whenever possible, because those studies are where the questions can be resolved.

"We need to double down on doing more of these trials and doing them even more rapidly," he says. "That's been one of the things that has advanced many fields of medicine, and it's certainly true of COVID-19."

When clinical trials aren't practical for his patients, he discusses the pluses and minuses of treatment to help them decide. Use of these drugs has been uneven, partly because they must be infused into a vein, which is a labor-intensive process.

A lot of the improvement in survival from COVID-19 is because doctors have learned a lot about how to manage the disease. Relatively simple steps, like turning patients over and providing blood thinners, have benefitted patients. New medicines, and new ways of using old drugs, are also helping.

One drug that has been found to be effective in clinical trials is remdisivir. It targets the virus and appears effective in shortening hospital stays for some of the sickest patients. It has not been shown to save lives.

Remdesivir has received full approval from the Food and Drug Administration, even though a large global study failed to find it effective and the World Health Organization recommends against its use. Medical science is all about weighting the available evidence, and different organizations don't always see eye to eye.

More impressive is the effectiveness of the steroid, dexamethasone, which helps tamp down potentially deadly immune system flare-ups.

"Dexamethasone does appear to be life saving for those sickest patients," says Dr. Francis Collins, director of the NIH, "but it's a pretty big sledgehammer in terms of what it does to the immune system. Maybe there's something a little more subtle that would be even more effective with less in the way of side-effects."

There are many studies underway right now to test about a dozen potential candidates. This is one of the most eagerly watched areas of research, both by doctors looking for better treatments and investors hoping that one of these drugs will be a real moneymaker.

The FDA has authorized one such drug for emergency use, baricitinib, when given together with remdesivir. Authorities in the United Kingdom have also given the nod to a second drug that tamps down a dangerous immune reaction, tocilizumab.

Collins hopes that scientists and drug companies will ultimately develop medicines that target the virus itself, to snuff out infection. That strategy worked for drugs targeted at HIV, making it a manageable disease. This approach will almost certainly involve multiple drugs, each targeting a different feature of the coronavirus.

Early on in the pandemic, scientists hoped they would find highly effective drugs that are already on the market for other purposes, but that doesn't look promising.

"If you really want the potent combination therapy that's incredibly effective against this coronavirus, we probably don't have that in front of us and we have to go out and find it," Collins says.

There is a substantial effort underway to develop these drugs from scratch. Some of that work was discussed in a November NIH workshop. The task involves identifying the targets to attack – ideally enzymes that are unique to coronaviruses. Once those targets are in the crosshairs, scientists examine tens of thousands of chemical compounds to see which will interfere. From there, it's still a challenge to develop a drug that will be highly effective but not too toxic.

Collins thinks that process could take three years. He would like to find drugs that target not just this coronavirus, but would work against any future coronavirus that starts spreading in people.

"You would be in a much better position to deal with whatever's coming down the road," he says. "Heck, we might even cure the common cold because a lot of those are caused by coronaviruses, too. What a nice spinoff that would be!"

In fact, that's often how research works: A blend of basic research and serendipity often open unexpected avenues for researchers to pursue. Every now and then, that pays off.

You can contact NPR Science Correspondent Richard Harris at rharris@npr.org.

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