Clinical study shows drug has COVID-19 treatment potential
Drug developer Noxopharm has announced that in a study of 18 patients diagnosed with moderately severe cases of COVID-19, its candidate Veyonda was shown to protect against the progression of cytokine storm, a severe inflammatory condition associated with worsening of the disease. Graham Kelly, CEO of Noxopharm, shared the history of the drug, details of the study, and the next steps.
OSP: Could you please tell us a little bit of the history of Veyonda—discovery/development, the path of exploring its potential anti-cancer benefits, etc.?
GK: The API in Veyonda is the small molecule, idronoxil. First identified as a human metabolite of the dietary isoflavone, daidzein, in 1993, it showed in the late-1990s to have potent ability to sensitize cancer cells to standard cytotoxic chemotherapies.
From 2000 to 2009, it underwent a series of Phase I, II, and III trials in collaboration with Yale University, focusing on restoring sensitivity to carboplatin in late-stage ovarian cancer. Trialing ceased in 2009 on the back of a futility assessment in its pivotal Phase III trial.
Development restarted in 2015 when its clinical failure was recognized as being associated with the oral route of administration. The drug was reformulated as a suppository dosage form and shown to be effective in a series of Phase I and II studies from 2016 to 2021.
OSP: Please tell us how Noxopharm came to realize the candidate could be useful in treating COVID-19 (specifically, preventing cytokine storm).
GK: Idronoxil was known to have some anti-inflammatory properties that were considered contributory to its anti-cancer function. The nature of this function was studied in 2019, focusing on the likelihood that it was serving as an agonist or antagonist to the STING immuno-surveillance mechanism.
Idronoxil was confirmed as a potent inhibitor of the cGAS-STING pathway, operating via a novel mechanism. At that time, excessive STING activity was being implicated in the development of the cytokine storm leading on to septic shock, leading the company to consider testing Veyonda as a preventative of septic shock; that consideration coincided with the realization in early 2020 that much of the death in COVID-19 patients was associated with septic shock.
OSP: Could you please provide a little more detail about the study and the 18-patient cohort from which you gathered this potentially hopeful data?
GK: The NOXCOVID study is a pilot study being conducted in three European hospitals and involves 40 patients hospitalized with moderately severe ARDS requiring supplementary oxygen. The patients meet categories 3 and 4 on the WHO COVID-19 scale.
The primary endpoints were safety and efficacy (clinical response and blood biomarkers of disease severity). The first 24 patients were in the dose-response arm (Veyonda dosages 400 mg – 1800 mg) and the last 16 patients in the dose-expansion (1800 mg) arm. The interim reported to date is on the first 18 patients.
OSP: Could you provide a little more detail about what you’re expecting (hoping) to happen after the final data review, consulting with regulators and business dev team, etc.?
GK: While the next steps will depend on the final report, a major area of interest will be on the ability of Veyonda to block blood levels of the various biomarkers now linked to COVID-19 severity. The ability to block elevation of a range of cytokines and other markers would distinguish Veyonda as a potential means of preventing COVID-19 patients from progressing from requiring minimal health care to intensive care.
Following the review of data, a larger controlled trial is an obvious next step, in consultation with regulators and sources of non-dilutive funding.
OSP: Do you have anything else to share about Veyonda?
GK: Veyonda is being developed primarily as an anti-cancer agent, with its oncolytic and immunostimulatory actions being used to enhance the effectiveness of standard anti-cancer therapies such as cytotoxic chemotherapy, radiotherapy, and checkpoint inhibitor therapy.