26 October 2020 - - US-based biotechnology start-up ANA Therapeutics has begun a multicenter, Phase 2/3 clinical trial to evaluate the safety and efficacy of its proprietary, oral niclosamide (ANA001) formulation for the treatment of patients with moderate COVID-19 disease, the company said.

The trial is the first in the US to test the potential of niclosamide, a drug with a long history of use in treating tapeworm, for COVID-19, the disease caused by SARS-CoV-2.

Niclosamide, which is not currently available in the US, has been used for more than 50 years to treat millions of people worldwide, with its primary indication being the treatment of tapeworm infections.

The drug recently emerged as a promising candidate for treating SARS-CoV-2.

In pre-clinical research by an independent academic group published in Antimicrobial Agents and Chemotherapy, niclosamide inhibited viral replication in vitro and was more potent than remdesivir in the same assay.

The mechanism of action for niclosamide's inhibition of SARS-CoV-2 is believed to be through SKP2-inhibition.

In a preprint, an independent academic group reported niclosamide prevents SARS-CoV-2 replication via SKP2-inhibition.

The same group previously reported in Nature Communications that niclosamide prevents the replication of Middle East respiratory syndrome (MERS-CoV), a coronavirus closely related to SARS-CoV-2, by the same mechanism.

In addition to its antiviral properties, niclosamide has shown anti-inflammatory activity through NF-κB and STAT3, transcription factors that induce the expression of molecules that drive inflammation. 

In vitro experiments reported in Cancer Research and ACS Medicinal Chemistry Letters, respectively, demonstrated that niclosamide inhibited both NF-κB and STAT3 transcription.

The Phase 2/3 trial is a randomized, placebo-controlled study that will be conducted in two parts at a total of 20 clinical sites in the US In both study parts, hospitalized patients with moderate COVID-19 (patients not requiring ventilators) will be administered a seven-day course of niclosamide capsules in addition to standard of care.

The primary objective of the first part of the trial is assess safety and tolerability; secondary objectives include measurement of efficacy (median time to discharge) and pharmacokinetics.

The trial's second part will enroll several hundred patients, with the primary objectives of assessing niclosamide's efficacy (median time to hospital discharge), safety and tolerability. Secondary objectives relate to clinical improvement and the need and duration for rescue therapy.

ANA Therapeutics is a Silicon Valley-based biotech start-up developing a proprietary niclosamide formulation as a widely accessible antiviral treatment for patients with COVID-19. ANA Therapeutics is the first Y Combinator portfolio company to initiate a Phase 2 clinical trial.