Australia-based drug development company Noxopharm has started its Noxocovid clinical program with a planned Phase I trial in Europe. The effort is geared toward gathering safety data and proof-of-principle regarding the use of Veyonda, a drug currently used to block cGAS-STING signaling.
The purpose of the trial is to determine Veyonda’s potential use as a treatment for cytokine storm and septic shock, both of which have emerged as significant causes of morbidities and death in COVID-19 patients.
A cytokine storm involves an over-abundance in the blood of multiple proteins known as pro-inflammatory cytokines. Inhibiting single cytokine members of that storm has to date not proved effective in preventing COVID-19 deaths.
Noxopharm CEO Graham Kelly told Outsourcing-Pharma that treatment of cytokine storm has proven a formidable challenge in the battle against COVID-19.
“Just as in diseases like rheumatoid arthritis, a cytokine storm involves out-of-control levels of multiple cytokines,” he said. “In the case of COVID-19, about six cytokines have been identified as being prominent players; we only have current drugs for two of those cytokines.”
Kelly added that both drugs used for cytokine storms have been tried on COVID-19 patients—unfortunately, with no reported benefit.
“The challenge therefore appears to be the need to block the production of a wide range of cytokines,” he explained.
According to Noxopharm, a more feasible approach may be to ‘go further upstream’ to target the cytokine storm at its source (likely the cGAS-STING pathway) is becoming increasingly seen as that headwater.
Septic shock, another condition common in COVID-19 patients, also occurs in patients suffering from a range of other conditions, Kelly told us.
“Any virus (or bacteria) is capable of inducing septic shock; most deaths from seasonal influenza outbreaks are due to septic shock,” he commented. “In the case of COVID-19 patients, the cytokine storm occurs in those patients who develop severe lung inflammation; this lowers their ability to absorb oxygen, with the resulting hypoxia causing damage to major organs such as the heart, liver, kidneys and brain.”
“This extensive damage is what triggers an over-exuberant inflammatory response = cytokine storm,” Kelly explained.
Noxopharm announced in April that laboratory studies revealed one of the mechanisms of action of idronoxil, the active ingredient in Veyonda, is to block the cGAS-STING signaling pathway, including the overexuberant STING and cytokine response to the sort of hypoxic tissue damage associated with low body oxygen levels in COVID-19 patients suffering severe respiratory distress.
Certain cancers (such as prostate cancer and colorectal have been associated with ‘bad’ inflammation and anti-inflammatory drugs (like prednisone) have been shown to be helpful in the treatment of those cancers. According to Noxopharm, encouraging clinical results using Veyonda in end-stage prostate cancer moved researchers to explore if this could be aid COVID-19 patients as an active inhibitor of the STING pathway.
Kelly told us the company is eager to test Veyonda’s effectiveness in treating COVID-19 patients, and protecting against cytokine storm and septic shock.
“The purpose of this Phase I study is to test this theory in a clinical setting as quickly and as cost-effectively as we can,” he said. “While Veyonda is first and foremost an anti-cancer drug, a successful treatment of septic shock represents both an enormous commercial opportunity and a pressing humanitarian need that we cannot ignore.”