“There is a big need for a drug in outpatients. If you could treat them and keep them out of hospitals, that would be important and play a big role in getting us through this pandemic,” Romark Laboratories LC’s CEO, Marc Ayers, told BioWorld.
As yet, those kinds of treatments have been elusive. However, Ayers said the initial results from Romark’s phase III study of NT-300 (nitazoxanide extended release) vs. placebo in treating outpatients with mild or moderate COVID-19, especially in the secondary endpoint, are encouraging enough to seek an EUA.
The median time to sustained response, the primary endpoint, was about 13 days, similar to NT-300-treated subjects treated with placebo. A predefined subgroup of patients with mild disease demonstrated a median time to sustained response was reduced by 3.1 days with NT-300, a viral replication inhibitor, vs. placebo.
In a secondary endpoint analysis, NT-300 was tabbed with an 85% reduction in progression to severe illness, which generally requires hospitalization, with only one subject moving on to severe COVID-19.
In the predefined subgroup at high risk of severe illness according to CDC criteria, 5.6% of the placebo-treated subjects experienced severe illness compared to 0.9% of the NT-300-treated subjects.
With those positive data in hand, Tampa, Fla.-based Romark said it plans to seek an emergency use authorization (EUA) from the FDA.
“The numbers are also very comparable to the numbers we’ve seen for monoclonal antibodies with an EUA,” Ayers said, adding that NT-300 has an advantage by virtue of its oral administration. Ayers also said the company is supplying the FDA with the information it needs but there is no specific timetable for further action that has been announced.
The phase III study started in August and wrapped up in February. There were 1,092 participants in the randomized, parallel assignment, triple masked study. Male and female participants least 12 years of age had to show clinical signs and/or symptom that were consistent with worsening or stable mild or moderate COVID-19, including at least two respiratory symptom domains. They received two 300-mg nitazoxanide tablets or placebo twice a day for five days.
In April 2020, Romark said it planned to start two trials for prevention of COVID-19 and other viral respiratory illnesses in high-risk populations, including elderly residents of long-term care facilities and health care workers. In both studies, participants were to receive either NT-300 or placebo for six weeks, with the primary endpoint being the rate of COVID-19 illness for NT-300 vs. placebo.
Nitazoxanide was initially being developed by Romark to treat intestinal protozoan infections caused by Cryptosporidium parvum and Giardia lamblia but was found in preclinical studies to inhibit maturation of the SARS-CoV-2 spike protein.
“When COVID-19 came, it was then obvious and we saw an opportunity,” Ayers said. “We found in the lab that the product was effective very quickly and saw opportunity to do the development.” Romark then went directly into its phase III study.
Others are developing outpatient COVID-19 therapies. In July, AI Therapeutics Inc., of Guilford, Conn., began a randomized, double-blind, placebo-controlled study of up to 142 outpatients treated with LAM-002A to reduce viral load. LAM-002A is a PIKfyve kinase inhibitor that has demonstrated potent in vitro antiviral activity against several isolates of SARS-CoV-2, the virus responsible for COVID-193,4. Indeed, several studies now have shown that LAM-002A interferes with the entry and trafficking of the SARS-CoV-2 virus in cells. In July, AI Therapeutics, Yale University and the Quantitative Biosciences Institute at the University of California, San Francisco, began a phase II study of LAM-002A, with a primary efficacy endpoint being reduction of viral load in those with confirmed infection. Additional efficacy measures include death, hospitalization and oxygen saturation.
In October, a phase I collaboration of Niagen (nicotinamide riboside) by Chromadex Corp. and Scandibio Therapeutics AB showed a 29% reduction in recovery time in 100 outpatients who received standard of care and nutritional protocol that included the agent, reducing average recovery time to 6.6 days vs. 9.3 days for placebo.
A study of Reeqonus (favipiravir; Avigan) for outpatients with mild to moderate COVID-19 continues in North America by Fujifilm Holdings Corp.