– NT-300 reduced progression to severe COVID-19 disease by 85%
– Romark is working with FDA and plans to seek Emergency Use Authorization in the U.S.
TAMPA, Fla. – April 14, 2021 – Romark announced today initial results of a Phase 3 clinical trial of its investigational new drug candidate NT-300 (nitazoxanide extended-release tablets, 300 mg) versus placebo as a treatment for mild or moderate COVID-19. Based on the findings, Romark is working with the U.S. Food and Drug Administration (FDA) and plans to seek Emergency Use Authorization (EUA).
In the analysis of the primary endpoint, median time to sustained response (a measure of recovery time) was similar for subjects treated with NT-300 compared with placebo (approximately 13 days). In the pre-defined subgroup of patients with mild disease, median time to sustained response was reduced by 3.1 days with NT-300 (10.3 days, n=116) versus placebo (13.4 days, n=129).
In the analysis of the key secondary endpoint, treatment with NT-300 was associated with an 85% (0.5% of NT-300-treated patients vs. 3.6% of patients treated with placebo) reduction in the progression to severe illness (shortness of breath at rest with SpO2 ≤93% on room air or PaO2/FiO2<300). Only one person treated with NT-300 progressed to severe COVID-19 disease. In the pre-defined subgroup at high risk of severe illness according to CDC criteria, 7/126 (5.6%) of placebo-treated subjects experienced severe illness compared to 1/112 (0.9%) of NT-300-treated subjects.
“Given the enormous toll of the COVID-19 pandemic and the continued public health risk, we are pleased that these clinical trial results show a compelling reduction in progression to severe COVID-19 with early NT-300 treatment,” said Jean-François Rossignol, M.D., Ph.D., Chief Medical and Scientific Officer of Romark. “Along with vaccines and treatments for severe illness, oral treatments that can be administered outside of a hospital setting to effectively reduce disease progression are urgently needed. Our results compare favorably with therapeutics that have been granted Emergency Use Authorization for use in a hospital setting in patients at high risk of developing serious COVID-19.”
The multicenter, randomized, double-blind trial (NCT04486313) studied 1,092 people ages 12 and older with respiratory symptoms consistent with COVID-19. Participants were enrolled at outpatient centers across the United States within 72 hours of symptom onset and treated either with two NT-300 tablets or placebo twice daily for five days. Efficacy analyses focused on the 379 participants who had laboratory-confirmed SARS-CoV-2 infection at baseline.
NT-300 was well tolerated. The only adverse event occurring in more than 2% of subjects was diarrhea (3.4% in the NT-300 group vs. 2.2% in the placebo group). There were no significant differences in adverse events between the two treatment groups.
Full findings from the study will be submitted for publication in a peer-reviewed journal. Results from an additional clinical trial for the prevention of COVID-19 and other viral respiratory illnesses in high-risk populations, including healthcare workers, are expected by the middle of the year.
Nitazoxanide, the active ingredient of NT-300, was originally developed for treating intestinal protozoan infections caused by Cryptosporidium parvum and Giardia lamblia. Laboratory studies demonstrating broad-spectrum antiviral activity led to the development of nitazoxanide as a broad-spectrum, host-directed antiviral drug.
In cell cultures, the active ingredient in NT-300, nitazoxanide, inhibits maturation of the SARS-CoV-2 spike protein, which in turn blocks SARS-CoV-2 syncytia formation. Nitazoxanide has also been shown to inhibit replication of SARS, MERS and other coronaviruses as well as influenza viruses, rhinoviruses, parainfluenza viruses, RSV and other respiratory viruses in cell culture studies.1-4 The broad-spectrum antiviral activity of nitazoxanide is attributed to its interference with human cellular pathways that the virus exploits to replicate, rather than to a virus-targeted mechanism.2,4
Laboratory studies to evaluate the potential for resistance of influenza A virus to tizoxanide, the active circulating metabolite of nitazoxanide, have been unable to select for resistant viruses, suggesting a low potential for viral resistance. Other studies have shown tizoxanide suppresses secretion of pro-inflammatory cytokines that are upregulated by viral respiratory infections including IL-6.5 The antiviral and anti-cytokine activities of nitazoxanide are attributed to modulation of mitochondrial function and consequential effects on cell signaling pathways.
NT-300 (nitazoxanide extended-release tablets) is an investigational broad-spectrum antiviral drug undergoing Phase 3 clinical development for treating and preventing acute respiratory illnesses caused by a broad range of seasonal, emerging or drug-resistant respiratory viruses, including influenza viruses, rhinoviruses, other enteroviruses, coronaviruses, parainfluenza viruses, respiratory syncytial viruses (RSV), human metapneumovirus or bocavirus.
The NT-300 tablets, administered orally, are designed to deliver antiviral concentrations of drug to the respiratory tract throughout twice-daily dosing. The 600 mg dose was selected based upon a dose-range-finding clinical trial conducted in outpatients with influenza.6 To date, clinical trials of NT-300 for treatment of viral respiratory illnesses have included more than 7,000 patients. The NT-300 clinical development program has been designed to provide robust evidence of effectiveness to support use of NT-300 and to ensure maximum benefit to the very large number of patients that experience these illnesses.
Romark is a vertically-integrated, research-based pharmaceutical company focused on the discovery, development and delivery of innovative new medicines, primarily in the field of infectious diseases. Romark has operations in the United States, Puerto Rico and Europe, and it conducts research and development and commercializes its products globally.
Romark is a leader in developing new drugs for treating a broad range of seasonal, emerging and drug-resistant viral respiratory illnesses. It is also developing a new product aimed at inducing functional cure of chronic hepatitis B. Products discovered, developed and commercialized by Romark have been used to positively impact the lives of more than 400 million people worldwide.
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1. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 0:1-3.
2. Rossignol JF. Nitazoxanide: A first-in-class broad-spectrum antiviral agent. Antivir Res 2014; 110:94-103.
3. Cao J, Forrest JC, Zhang X. A screen of NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs. Antivir Res 2015; 114:1-10.
4. Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health 2016; 9:227-230.
5. Hong SK, Kim HG, Chong CS, Choi IS, Lee JB, Park SY. Nitazoxanide suppresses IL-6 production in LPS-stimulated mouse macrophages and TG-injected mice. Int Immunopharmacol 2012; 13:23-7.
6. Haffizula J, Hartman A, Hoppers M, et al. A randomized, double-blind, placebo controlled clinical trial of nitazoxanide in adults and adolescents with acute uncomplicated influenza. Lancet Infect Dis 2014; 14:609-618.