There are currently zero authorized or approved preventative COVID therapies in the U.S. but Canadian biotech SaNOtize wants to change that, charting plans to move a nasal spray into a phase 3 study as soon as October.
It’s a deviation for the company that until now has been developing the nitric oxide nasal spray (NONS) as an early antiviral treatment, primarily assessing a reduction in viral load and testing time. But the takeaway from the company’s July 18 meeting with regulators was that those two markers wouldn’t be sufficient primary endpoints in a phase 3 treatment trial over a reduction in hospitalization or deaths. The problem—as has been exhibited by other potential COVID treatments—is that those latter data are difficult to accrue as much of the population has either vaccine-induced or natural immunity to the virus.
As a result, the company is pivoting, exploring the use of the spray as a preventative treatment, which, if successful, would be pursued as a direct over-the-counter med.
“There is no monograph right now for OTC antivirals—it doesn’t exist,” SaNOtize CEO Gilly Regev, Ph.D., said in an interview. “So it's a little bit of paving your own path, like we always need to do with nitric oxide. So it doesn't scare us.”
But Regev says the need to switch gears highlights a potential blind spot in regulators' gauge of valuable new treatments. That is to say, viral load may be worth paying more attention to as a marker of transmission.
“There needs to be a rethinking of regulators today of what's a reasonable primary endpoint that could allow people to get approval and early treatment because they are dismissing reduction of viral load,” she said. “Reduction of viral load means you will [test] negative, you can go back to work earlier."
Phase 3 data from SaNOtize’s ongoing trial in India published in the Lancet found that among treated patients, viral load dropped 93.7% within 24 hours and 99% within two days. That correlated with a median time to a negative PCR test of three days following treatment compared to seven days for the placebo group. The results were similar regardless of vaccination status or circulating variant. SaNOtize is pursuing authorization or approval as an early treatment in other regions, including Europe.
Past research has hinted at a possible relationship between viral load and infectiousness, although the jury remains out on a direct correlation. A study by German researchers in May 2021 of presymptomatic, asymptomatic, and mildly symptomatic COVID cases during the B.1.1.7 wave found that while viral load couldn’t be directly translated to transmission probability, "it is likely that the rapid spread of the B.1.1.7 variant is partly attributable to higher viral load in these cases.” The FDA would not comment on its discussions with SaNOtize or whether it was working with federal stakeholders to further study the relationship between viral load and infectiousness.
SaNOtize's plan now will be to launch a phase 3 trial in the U.S. sometime in October, either by initiating a brand-new study or expanding a trial already ongoing in Canada. But since the company will need enough participants to adequately assess the spray’s prevention abilities, the trial will likely be large and thus, costly. To pay for this, the company is currently in advanced talks with a number of global pharmaceutical companies interested in partnering up and is submitting a funding request to the U.S. Department of Defense.
Although using viral load data is off the table for the company’s phase 3 plans in the U.S., Regev said the FDA meeting was still helpful.
“There were a lot of people on that meeting, and they were super helpful with just guiding us of what the FDA would like to see,” she said. “We want to make sure that if we do a study, we follow their guidelines so we can eventually get approval.”