COVID-19 Drug Discovery for Early Treatment Lacking, But Needed

COVID-19 drug discovery efforts for early treatment of the virus in mild to moderate cases of the virus have been lacking even though successes now could mitigate the impact future outbreaks have on communities, according to NIAID Director Anthony Fauci, MD, and colleagues.

“Immediate benefits of treatments include improvement of patient outcomes and prevention of hospitalizations,” Fauci et al. wrote in a new JAMA Network Open viewpoint article.

“Longer-term benefits may include prevention of the chronic sequelae of infection as well as prevention of transmission by shortening the period of infectiousness. Outpatient treatments for COVID-19, coupled with an effective vaccine, would have significant implications for the ability to end this pandemic,” they continued. 
Just 20 percent of asymptomatic COVID-19 patients will progress to severe or critical disease. But patients who experience mild to moderate symptoms can experience prolonged course of recovery, including fatigue, cognitive impairment, and cardiopulmonary dysfunction. 

While treatment options for patients who are hospitalized with COVID-19 are widely available, there is a noteworthy absence of treatments proven to be effective for patients with early or mild infection, the experts from NIAID said. 

From drug discovery to clinical trials, the challenge of early treatment options must be addressed by both pharmaceutical companies and scientists, they urged. 

Currently, corticosteroids are the choice of treatment for critically ill COVID-19 patients. 

In mid-June, Oxford University released preliminary data from clinical trial, RECOVERY, which found that a commonly used steroid, dexamethasone, improved survival in hospitalized COVID-19 patients. 

At the time, dexamethasone was the first drug to be shown to improve survival in COVID-19 patients.

Then at the beginning of October, the New England Journal of Medicine (NEJM) released positive Phase 3 trial results for Gilead’s remdesivir, which showed that the antiviral was effective in reducing time to recovery in adults hospitalized with COVID-19. 

These results led to the FDA approval of remdesivir as the first COVID-19 treatment at the end of October.

The drug is now widely available in hospitals and other healthcare settings across the country and it is capable of providing acute care comparable to inpatient hospital care, according to FDA. 

“Both remdesivir and dexamethasone have been endorsed globally by multiple COVID-19 treatment guideline committees and have led to improvements in patient outcomes among those requiring hospitalization,” researchers highlighted. 

But these treatments have not been proven effective for individuals experiencing mild to moderate COVID-19.

For example, remdesivir is not suitable for an ambulatory setting because it requires daily infusions for up to 10 days. Meanwhile, dexamethasone has not been tested in early disease stages, but it could worsen clinical outcomes. 

However, Fauci and his colleagues identifies a few promising treatments for early COVID-19 coming down the pipeline.

Early-phase clinical trials of Eli Lilly & Company’s antibody, LY-CoV555, and Regeneron’s antibody, REGN-COV2, have shown promising results that suggest monoclonal antibodies may be effective in improving clinical outcomes in patients with early COVID-19. 

In mid-October, Regeneron announced that REGN-COV2 reduced viral load and alleviated symptoms in non-hospitalized coronavirus patients in a Phase 1/2/3 clinical trial. 

Specifically, the antibody reduced viral load through Day 7 in patients without an antibody presence (seronegative). 

And just last week, FDA recently issued an emergency use authorization for Eli Lilly’s LY-CoV555 for use in mild to moderate coronavirus in adults and pediatric patients.

The emergency use authorization allows healthcare providers to administer a single-dose of LY-CoV555 in infected patients 12 years of age or older as long as they weigh at least 88 pounds and to patients who are at risk for severe COVID-19 or hospitalization.

 These are both promising treatments for patients in the early stages of disease progression but de novo drug design approaches are still needed to refine current treatment methods and develop new drugs that can be administered in a less burdensome manner.

“Preventing hospitalizations and the chronic sequelae of COVID-19 will not only save lives, but also will help restore medical systems and other institutions that are overburdened by the effects of the pandemic,” Fauci et al. said.

“Effective, early treatments will also mitigate gaps left by previous and current prevention strategies and curtail forward transmission. These efforts deserve the full support of the medical community and the public,” they concluded.