Peer reviewed publication of phase III clinical trials on novel nitric oxide nasal spray for COVID-19 in Lancet journal

Nitric oxide is a naturally occurring molecule known to have antimicrobial properties, including a direct effect on SARS-CoV-2, the virus that causes COVID-19, and its variants. The study is titled, “SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomised trial.”

When beginning NONS treatment within three days of a positive COVID-19 test, viral load was reduced by approximately 94% within 24 hours of treatment and by 99% within 48 hours in participants at higher risk of disease progression, including older and unvaccinated patients. The study was carried out during the delta and omicron surges, suggesting that the treatment may be effective against variants of concern.

Study details: A randomized, double-blind, placebo-controlled study at 20 clinical sites across India evaluated 306 participants who had mild COVID-19 symptoms, confirmed with PCR test for SARS-CoV-2. Participants were enrolled in the study regardless of vaccination status (approximately 46% of participants were vaccinated).Participants were randomly assigned to self-administer either two sprays of NONS per nostril six times a day over a seven-day treatment period or saline spray (active placebo) in the same administration schedule. All participants had access to standard supportive care. A subgroup of particular interest was participants (n=218) with a high risk of disease progression, including non-vaccinated participants or those at least 45 years of age and/or with co-morbidities. Importantly, 58% of participants were enrolled during the second COVID-19 wave in India, in which the delta variant was predominant, and 42% during the third wave, in which the omicron and delta variants were predominant.

In the high-risk participants, NONS reduced the SARS-CoV-2 log viral load in COVID-19 patients by 93.7% within 24 hours of treatment and by 99% in 48 hours, compared baseline. At 48 hours of treatment, the reduction in viral RNA load was more than seven times greater in the NONS group compared to active placebo (P < 0.05). The average change from baseline in log viral RNA load through the entire length of treatment was statistically superior with NONS compared to placebo. Similar results were observed in vaccinated and unvaccinated populations. The median time to a negative a PCR test in the treatment group was three days vs. seven days after treatment initiation in the placebo group (P < 0.05).

Clinically, more patients receiving NONS (94%) were asymptomatic with no detectable SARS-CoV-2 RNA, based on the investigators’ WHO Clinical Progression Scale score improvement (two or more point reduction to a zero scale score), approximately one week after treatment compared to active placebo (81%; Day 16 treatment difference 12·6%, P < 0.05).

NONS was well tolerated, with no reports of moderate, severe, or serious adverse events. The most common side effect was nasal discomfort (reported by five participants in the NONS group and two in the placebo group).

The findings strongly mirror the reduction of viral load in an earlier Phase II trial (95% in 24 hours and 99% in 72 hours), conducted in the UK in March 2021 and published in the Journal of Infection.

Glenmark launched NONS under the brand name FabiSpray in February 2022, after receiving manufacturing and marketing approval from the Drugs Controller General of India (DCGI) as part of the accelerated approval process. NONS has already received a CE mark in Europe, which is an equivalent of marketing authorization in case of a Medical Device. By virtue of the CE mark, SaNOtize has permission to launch NONS in the EU. NONS is also approved and being sold in Singapore, Hong Kong, Israel, Thailand, Indonesia and Bahrain, under the name enovid™ or VirX™. Outside of India, NONS has also been approved globally for protection against viruses, including SARS COV-2.

See- J Infect. 2021 Aug; 83(2): 237–279.Published online 2021 May 13. doi: 10.1016/j.jinf.2021.05.009.PMCID: PMC8117664 PMID: 33992687 "Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection".;Stephen Winchester, Sarah John, Kashif Jabbar,and Isaac John.

See-"SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial";-Monika Tandon, Wen Wu, Keith Moore,Stephen Winchester,Yuan-Po Tu, Christopher Miller.et al. Open Access Published:July 12, 2022DOI:https://doi.org/10.1016/j.lansea.2022.100036.