Cancer Drug Fights COVID-19 Respiratory Deaths in Hospital Trial

Miami-based Veru announced positive results from its Phase II trial of its VERU-111 compared to placebo in hospitalized patients at high risk for Acute Respiratory Distress Syndrome (ARDS) from COVID-19.

VERU-111 is an oral, first-in-class, new chemical entity. It targets, crosslinks and disrupts alpha and beta tubulin subunits of microtubules. This appears to give it both antiviral and anti-inflammatory properties.

The trial was run in five sites across the U.S. Hospitalized patients with documented evidence of COVID-19 infection who were at high risk for ARDS were enrolled. Patients received a 19 mg dose of VERU-111 or a placebo in addition to standard of care for 21 days or until they were released from the hospital. The primary efficacy endpoint was the percentage of patients alive without respiratory failure at Day 29. Respiratory failure was defined as endotracheal intubation and mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive positive pressure ventilation and/or clinical diagnosis of respiratory failure.

The drug compared to placebo had a statistically significant and clinically meaningful decrease in the proportion of patients who were treatment failures. The rate was 5.6% in the VERU-111 treatment group compared to 30% in the placebo group, which is an 81% reduction in treatment failures.

“We are very pleased with the results of our Phase II trial, which demonstrated clinically meaningful reductions in relevant endpoints, including respiratory failure, days in the ICU and on mechanical ventilation and patient mortality,” said Mitchell Steiner, chairman, president and chief executive officer of Veru. “We believe VERU-111 has significant potential in treating COVID-19, both as a broad-spectrum antiviral and an anti-inflammatory agent, helping to prevent the effects that lead to ARDS and death.”

Standard of care treatment included Gilead’s remdesivir and/or dexamethasone. The use of either of those drugs did not appear to have any significant effect on patient outcomes in the trial. There were six patients in the entire trial that didn’t receiver either remdesivir or dexamethasone, four in the VERU-111 group and two in the placebo group. In the patients that received standard of care, VERU-111 treatment decreased days in the ICU by 1.43 plus or minus 3.96 days compared to 8.83 plus or minus 13.07 days in the placebo group and days on mechanical ventilation (VERU-111 zero days compared to placebo 6 plus or minus 10.57 days). No patients in the VERU-111 group and standard of care required mechanical ventilation.

Veru has received an expedited end-of-Phase II meeting with the U.S. Food and Drug Administration (FDA) to discuss the path forward, including a Phase III clinical registration trial design for the VERU-111 COVID-19 program. Veru expects the trial design will be similar to that of the Phase II trial, but will be run in about 200 hospitalized patients.

The company thinks it has enough supply of the drug to complete the Phase III trial. Once they get the go-ahead from the FDA, they hope to start the Phase III trial in April and conclude by the fourth quarter of 2021. They’re looking for funding from The Biomedical Advanced Research and Development Authority of the U.S. Department of Health and Human Services (BARDA) and other agencies to fund the amount of commercial drug needed for the U.S. population, assuming they have positive clinical results and FDA approval. A meeting with BARDA to discuss potential grant funding for the Phase III trial and manufacturing scale-up is already planned.

The drug was originally designed to treat cancer. Microtubules, which are what VERU-111 targets, are the transportation system within cells.

“Viruses are macromolecules," Steiner told BioSpace in August. "To block replication, you have to hijack the cell replication machinery. Otherwise, the virus enters the cells, hops onto the microtubules which, like a taxicab, bring the viral RNA to the nucleus for replication, where the virions assemble into new virus particles, which hop back to the microtubules to exit the cell.”

The drug is derived from colchicine, a drug used in variety of laboratory methodologies and horticulture, as well as to treat gout, because it disrupts cell replication. In COVID-19, it blocks the ability of antigen receptors to be transported into the nucleus of a cell or out again. Basically this means it prevents viral particles from entering the cell (or getting out again). The company is otherwise developing the drug for prostate cancer, where it is in clinical trials.

Steiner, of today’s announcement, said, “We have the resources to conduct a Phase III trial without impacting our cancer drugs’ clinical development. We look forward to our upcoming discussion with FDA concerning the regulatory and clinical development steps to move VERU-111 for COVID-19 forward.”