Interest in testing the mettle of three widely available drugs against COVID-19 gained traction Monday, led by suggestions that daily low-dose aspirin might lower the risks of complications and death from the disease.

Aspirin use was associated with a 44% reduction in the risk of being put on a mechanical ventilator, a 43% decrease in the risk of ICU admission and a 47% decrease in the risk of dying in the hospital compared to those who were not taking aspirin, researchers at the University of Maryland School of Medicine (UMSOM) said. The findings, published in Anesthesia and Analgesia, supported "cautious optimism" that the inexpensive medicine could prevent severe complications, the researchers said.

"We believe that the blood thinning effects of aspirin provides benefits for COVID-19 patients by preventing microclot formation," said study co-author Michael Mazzeffi, an associate professor of anesthesiology at the school.

The retrospective, observational cohort study looked at adult patients with COVID-19 admitted to multiple hospitals across the U.S. between March and July, controlling for both demographic factors and co-morbidities. Next, the researchers advised, "a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients." UMSOM assistant professor Jonathan Chow led the study.

Can tapeworm-fighter beat COVID?

Despite being the only household name under consideration for COVID-19 care on Monday, aspirin wasn't the only long-lived medicine in the news. Separately, Foster City, Calif.-based ANA Therapeutics Inc. began a phase II/III trial testing a its oral niclosamide formulation, ANA-001, for the treatment of patients with moderate COVID-19.

Long used in treating tapeworm infections across millions of people worldwide, niclosamide isn't currently available in the U.S. But with preclinical research suggesting it might be even more potent than remdesivir for inhibiting viral replication, ANA's team has organized a randomized, placebo-controlled study to evaluate the drug's use in addition to standard of care.

The primary objective of the first part of the trial is to assess safety and tolerability. The secondary endpoints include measurement of efficacy, such as median time to discharge and pharmacokinetics. The trial's second part will enroll several hundred patients, with the primary objectives of assessing niclosamide’s efficacy (median time to hospital discharge), safety and tolerability.

Y Combinator, the Silicon Valley-based seed funder that's backing the company, said ANA is the first of its portfolio companies to initiate a phase II trial.

A targeted therapy

Though also long-lived in the annals of medicine, sodium nitrite could be put to new use if Austin, Texas-based Nitric Oxide Innovations LLC succeeds in its work. As part of the U.S. Coronavirus Treatment Acceleration Program, the company said it has gained IND clearance to start a double-blinded, placebo-controlled phase IIb/IIIa trial of its new drug, Noviricid, a 30-mg dose of sodium nitrite in an oral lozenge.

Nitric oxide has been tested by several other companies for the treatment of COVID-19, such as Novan Inc. and Bellerophon Therapeutics LLC. But Noviricid is the first oral NO-generating drug to be specifically tested to treat African Americans diagnosed with COVID-19, the company said.

The company is aiming to enroll 840 African American COVID-19 patients, each within 72 hours of them testing positive for the infection. Furthermore, study participants will need to present with one or more co-morbidities, such as high blood pressure, chronic obstructive pulmonary disease, heart failure, diabetes or obesity.

"Everything we have learned about COVID-19 over the past 10 months reveals that diminished nitric oxide production in patients is what is thought to be responsible for the increased risk of infection and rapid disease progression," said company CEO Nathan Bryan. "This applies directly to the African American population, which often suffers from diminished nitric oxide production."

According to CDC statistics cited by the company, African Americans experience a 2.8 times higher SARS-CoV-2 infection rate, a 4.7 times higher hospitalization rate and 2.1 times higher death rate than Caucasians.

One less trial

Meanwhile, hopes that a newer medicine might provide benefits against the infection have been shelved, sending shares of Biosig Technologies Inc. (NASDAQ:BSGM) down 39.6% on Oct. 26 to close at $3.03.

Officially advanced by Biosig subsidiary Viralclear Pharmaceuticals Inc., the now-sidelined antiviral merimepodib was reported in July to have demonstrated strong activity against SARS-CoV-2 in cell cultures. However, after a safety monitoring committee determined that "an imbalance in survival rates" between the study drug and placebo arms of a phase II trial made clear the trial's primary safety endpoints wouldn't be met, Viralclear decided to quit study enrollment. Furthermore, Biosig said it would discontinue development of the drug, putting it up for sale or licensure, it said.

Merimepodib was under evaluation in combination with Veklury (remdesivir, Gilead Sciences Inc.) as a possible therapy for seriously ill patients who required high flow, high concentration oxygen to maintain adequate oxygenation.

It was unclear whether preclinical testing of merimepodib with a Sorrento Therapeutics Inc. neutralizing antibody candidate, announced earlier this month, would go forward. That study was designed to look for synergy between the experimental medicines in strengthening and accelerating viral clearance of SARS-CoV-2.

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