The findings of a recent Phase IIa clinical trial suggest that OP-101, a hydroxyl-polyamidoamine dendrimer–N-acetyl cysteine conjugate, may have potential for treating systemic hyperinflammation in severe COVID-19.

A single intravenous infusion of the anti-inflammatory compound was well tolerated and reduced the risk of death or mechanical ventilation at 30 and 60 days after treatment when compared to placebo. OP-101 treatment, which targets activated macrophages, was associated with decreased serum concentrations of proinflammatory markers as well as markers of neurological injury (neurofilament light chain and glial fibrillary acidic protein). The drug may have the potential to treat systemic inflammation and brain injury in patients with severe COVID-19 and significantly reduce their chances of death.

The results of the trial were published in Science Translational Medicine in the article, “Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a Phase IIa clinical trial.

In the randomized, double-blind, placebo-controlled, adaptive Phase IIa trial, 24 patients classified as having severe COVID-19 across five clinical sites in the United States were randomized to receive a single intravenous dose of placebo (n = 7 patients) or OP-101 at 2 (n = 6), 4 (n = 6), or 8 mg/kg (n = 5 patients). All patients received standard of care, including corticosteroids.

“OP-101 is a novel nanotherapeutic compound that specifically targets activated macrophages and microglia, the primary immune cell in the brain,” said Aaron M. Gusdon, MD, assistant professor in the Vivian L. Smith department of neurosurgery with McGovern Medical School at UTHealth Houston. “Due to its excellent safety profile, we were excited to offer this therapy to these critically ill patients at Memorial Hermann Hospital.”

Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity in COVID-19. OP-101 was found to be better than a placebo at decreasing inflammatory markers, as well as better at reducing markers of neurological injury, including neurofilament light chain and glial fibrillary acidic protein.

Additionally, risk for the composite outcome of mechanical ventilation or death at 30 or 60 days after treatment was 71% for patients receiving the placebo, but just 18% for patients in the pooled OP-101 treatment arms. At 60 days after treatment, 3 of 7 patients given placebo and 14 of 17 patients treated with OP-101 survived.

The data shows that OP-101 was well tolerated in the critically ill patient population and could serve as an effective treatment for patients hospitalized with COVID-19.

“Although this was a small-dose escalation trial, there was clearly a strong signal toward benefit at both acute and chronic timepoint,” Gusdon said. “The possibility that this therapy could also benefit patients with other diseases that lead to systemic inflammatory responses, including various forms of brain injury, is extremely exciting.”