02:45 - Source: CNN
Covid-19 deaths remain high as vaccine optimism grows

Editor’s Note: Kent Sepkowitz is a CNN medical analyst and a physician and infection control expert at Memorial Sloan Kettering Cancer Center in New York. The views expressed in this commentary are his own. View more opinion at CNN.

CNN  — 

Hydroxychloroquine is back! And this time it has brought not only hot-aired discussion but space aliens and demon sperm!

Yes, it’s true, the supposed miracle cure for Covid-19 that is really no cure at all, is all over the news again, thanks to President Donald Trump and a group of true believers, who are re-upping their endorsement of its all-around wonderfulness.

Though distracting, the attention hydroxychloroquine is drawing raises a different but very important issue: whatever happened to the relentless US search for a Covid-19 cure?

Kent Sepkowitz

Right now, we have three sort-of therapies for people with active infection, each with substantial limitations. Remdesivir is a new, expensive antiviral drug with modest benefit that must be given intravenously and is in short supply.

Dexamethasone is a potent corticosteroid that has been around for decades. It is cheap and effective if you are quite ill, but not proven useful for mild or moderate disease.

The third entry, convalescent plasma, has been around even longer. A version of it was given during the 1918 Spanish Flu pandemic. It is cheap and available but requires a human source and must be given intravenously. Optimal use of these three therapies, including administering two or even all three together, has not been determined.

Only one of these drugs, Remdesivir, has an emergency use authorization from the US Food and Drug Administration, allowing it to be used in persons with “severe disease.” Current evidence has not established that it gives patients a survival advantage, although those who do survive recover faster.

It turns out that while we have all been buzzing about hydroxychloroquine and the tantalizing race for a someday vaccine, too often we have been dismissive of the actual, not hypothetical, good thing in front of us – direct treatment of the infection – like an old high school friend you wish had never called.

Sure, the vaccine race is a great story, full of high-tech science, international intrigue and lots of money. Naked DNA and viral vectors and spike proteins are all very cool sounding for sure – but this doesn’t mean vaccines will solve the Covid-19 pandemic any time soon.

Maybe, with luck, in a few months we will have a probably-not-unsafe vaccine that shows some evidence of benefit for an uncertain duration in some patients. Maybe it will be made in China or Russia or some other country with which we have relationship issues.

The FDA has tried, haltingly, to generate enthusiasm for its therapeutics program by rebranding it with a new acronym. The Corona Treatment Acceleration Program, or CTAP, has a dashboard (last updated on June 30) that lists more than 510 therapies in planning stages, more than 230 trials reviewed and considered by FDA to be “safe to proceed” forward, two treatments that have received authorization for emergency use (including the now rescinded authorization for hydroxychloroquine) and zero approved agents.

For me, the explanation for the paucity of treatments currently under study is demonstrated in the second figure on the FDA website titled “type of Covid-19 treatment being studied.”

Of the trials considered safe enough to proceed, more than 70 are immunomodulator and about 20 are highest tech cell and gene therapies. Neutralizing antibodies – scientifically akin to convalescent plasma – account for about 30 other trials.

The smallest group under development is antivirals, which happen to be the one proven effective way to treat viral infections. We have effective antivirals for many diseases including herpes (simplex and zoster), HIV, hepatitis B and hepatitis C.

These medications have saved lives and reduced transmission of infection. Yet a look at the 298 active US interventional trials listed on clinicaltrials.gov demonstrates a pronounced lack of antivirals under study.

The antivirals tested thus far are retreads, developed for other diseases. This makes sense: reaching for already developed medications is the first order of business in an emergency. These include lopinavir-ritonavir (Kaletra™), a drug approved for HIV infection that was ineffective for Covid-19, oseltamivir, an influenza medication that similarly fell short against Covid-19 and remdesivir itself, which was developed to treat Ebola.

Still under study are favipiravir, approved in Japan for influenza years ago, though little used, which is currently in Phase 2 trials in the US for Covid-19 infection and LAM-002A, previously tried in lymphoma treatment, which may interfere with viral attachment and be useful in early Covid-19. A few others also are getting a look.

Certainly, the time required to develop drugs is famously long and expensive. But then, so is development of a vaccine.

So why the slow roll? Granted, few of the deaths in Covid-19 infection are directly from viral invasion. Covid-19 kills by provoking overwhelming inflammation that damages heart, lung, brain and blood vessels. Inflamed blood vessels promote clotting.

One might argue that treatment to blunt the downstream effect of the virus, rather than the virus itself, may be appropriate.

Indeed a government-industry partnership called ACTIV (Accelerating Covid-19 Therapeutic Interventions and Vaccines) has prioritized reduction of inflammation and of clotting, as well as synthetic products that mimic the effect of convalescent plasma.

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I imagine this approach is less due to scientists’ views on the cause of death and more due to the notion that one drug for one disease really doesn’t cut the mustard anymore, at least from a commercial perspective.

The larger interest is to develop “platforms” for broader discovery, such as playing with the immune system, where insights from Covid-19 may have applicability to additional diseases, including cancer or arthritis.

This is a great long-term business strategy but wrong-headed in the midst of a crisis. When the house is burning down, you want the best firehose, not a disruptive technology that promises a new way to separate water into component molecules that can to be sent to a repository 600 miles away at the speed of light, reconstituted and dispersed over the flames.

The latter approach, if successful, may change society as we know it; but the former will keep people from burning to death.

With more than 4.5 million cases of Covid-19 in the US and more than 150,000 deaths in just seven months, it is time for the brilliant dreamers who lead our science labs to do the seemingly impossible: change course and begin to think small.