AzurRx BioPharma Initiates Phase 2 Clinical Trial of Niclosamide for the Treatment of COVID-19 Gastrointestinal Infections

AzurRx BioPharma, Inc. recently announced it has initiated its Phase 2 RESERVOIR clinical trial of a proprietary oral formulation of micronized niclosamide (FW-1022) for the treatment of COVID-19-related gastrointestinal (GI) infections. Patient enrollment is expected to begin in April 2021 with topline data anticipated in Q1 2022.

The Phase 2 RESERVOIR clinical trial is a two-part, two-arm, placebo-controlled study examining the safety and efficacy of micronized oral niclosamide tablets, known as FW-1022, in patients with COVID-19 GI infection. The two primary objectives of this trial will be to confirm the safety of niclosamide in the treatment of patients with COVID-19 GI infection and to demonstrate efficacy in clearing the SARS-CoV-2 virus from the GI tract. The primary efficacy measure of the RESERVOIR trial is the rate of fecal SARS-CoV-2 virus clearance (rectal swab or stool sample) assessed by RT-PCR, comparing the niclosamide arm to the placebo arm for up to 6 months. These long term observation data could indicate that niclosamide treatment has the potential to improve “long haul” COVID-19 symptoms.

As previously announced, the trial will be managed by PPD, Inc., a leading global contract research organization (CRO).

“Initiation of the Phase 2 clinical trial of FW-1022 for the treatment of COVID-19 GI infection, or the RESERVOIR trial, is a significant milestone for AzurRx and an important advance in the ongoing battle to help those infected by COVID-19 to overcome the often long-lasting effects of the virus,” said James Sapirstein, Chairman, CEO and President of AzurRx BioPharma. “COVID-19 is a pernicious disease and, despite the ongoing vaccine rollout, one that continues to impact hundreds of thousands of people worldwide every day in addition to the millions who have already been infected. For many, the after-effects of COVID-19 can be as bad as the disease itself, and this includes a growing number who experience severe GI complications due to what many believe is the ability of SARS-CoV-2 to hide in reservoirs within the GI tract. We believe micronized oral niclosamide has the potential to target SARS-CoV-2 directly in the gut and, doing so, become an important addition to the armamentarium of therapeutics that will unfortunately be required by many who contract COVID-19.”

“So called ‘long haul COVID’ cases are becoming a major problem globally, and it is reasonable to expect the GI tract may serve as a silent reservoir,” added Dr. James Pennington, Chief Medical Officer of AzurRx. “We believe that niclosamide is ideally equipped to eradicate these hidden GI SARS-CoV-2 reservoirs due to its proven safety profile, known effectiveness in treating other GI ailments, and unique ability to remain in the gut for long periods of time. These properties, we believe, will be accentuated by our micronized formulation of niclosamide, which allows for local concentrations in the gut that exceed those needed to kill SARS-CoV-2. We look forward to testing this hypothesis in the RESERVOIR Phase 2 trial and reporting topline data from the trial in early 2022.”

More information about this clinical trial is available at ClinicalTrials.gov.

The Phase 2 RESERVOIR clinical trial is a two-part, two-arm, placebo-controlled study examining the safety and efficacy of an immediate-release capsule formulation of micronized oral niclosamide, known as FW-1022, in patients with COVID-19 GI infection. The two primary objectives of this trial will be to show safety of niclosamide in treatment of patients with COVID-19 GI infection, and to show efficacy in clearing the SARS-CoV-2 (SARS2) virus from the GI tract.  Part 1 of the trial will study 9 to 18 patients hospitalized with COVID-19 and GI positive stool or rectal swabs for SARS2.  Patients will be treated for 14 days and observed closely for any signs of safety issues.  A Data Monitoring Committee will then review the safety profile and if niclosamide is well-tolerated, the trial will move on to Part 2.

Part 2 will be conducted in outpatients with COVID-19 and PCR positive stool or rectal swabs for SARS2.  Patients will be randomized to either niclosamide, 400 mg tablets, three times a day, or placebo tablets three times a day.  After 14 days of treatment, patients will be taken off study drugs and remain on study observation for up to 6 months. The primary efficacy measure of the trial is the rate of fecal SARS2 virus clearance (rectal swab or stool sample) assessed by RT-PCR, comparing the niclosamide arm to the placebo arm. Long term observation will also be important to indicate whether niclosamide treatment might improve ‘long haul’ COVID-19 symptoms.  Approximately 100 patients will be studied in Part 2.

An IND for the trial has been approved by the FDA, and the trial expects to begin enrolling patients in April 2021. Top line data are expected Q2 2021.

Gastrointestinal infection symptoms (severe diarrhea, vomiting and abdominal pain) have been reported in approximately 18% of COVID-19 cases. Of the 26.6 million individuals who are reported to have contracted COVID-19 in the U.S., this would translate into 4.8 million patients having GI infection. Of the 105 million cases globally, it would translate into almost 19 million patients.

There is some evidence to support the view that the GI tract is a possible reservoir for recurrence and fecal spread of the COVID-19 virus as ACE-2, the entry receptor for COVID-19, is highly expressed on GI cells. There currently is no targeted treatment for COVID GI infections.

Niclosamide is a prescription small molecule drug listed as an essential medicine by the World Health Organization (WHO). Niclosamide has been safely used on millions of patients for other clinical indications.  In the US, niclosamide was approved by the U.S. Food and Drug Administration (FDA) in 1982 for the treatment of intestinal tapeworm infections. In addition to its antihelminthic activity, niclosamide has demonstrated anti-inflammatory and anti-viral properties.

There remains an urgent need to develop new medicines that can be manufactured at large scale quickly to treat COVID-19. Niclosamide was recently identified by the Institut Pasteur Korea as a potent inhibitor of SARS-CoV-2, the virus causing COVID-19, with potency 40X greater than remdesivir. Additionally, emerging evidence confirms the severe GI-related complications of COVID and potential fecal spread of the virus. The company’s clinical trials may establish that patients treated with an oral and non-systemic niclosamide formulation that delivers high local GI concentrations have decreased viral load and GI-associated symptoms of COVID. Importantly, the manufacturing process for niclosamide can be scaled up to supply large populations quickly.

FW-1022 is a niclosamide based small molecule which the Company’s clinical trials may establish has anti-viral activity that is effective for the treatment of SARS-CoV-2 (COVID-19) gastrointestinal infections. FW-1022 will be supplied as an oral immediate release tablet. The formulation to be used has been milled (micronized) to allow superior dissolution in the gut fluids. This in turn may allow local niclosamide concentrations to reach anti-viral levels. Thus, FW-1022 has the potential to benefit COVID patients by decreasing viral load in the GI tract, treating infection symptoms and preventing transmission of the virus through fecal spread.

AzurRx BioPharma, Inc. is a clinical-stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases. The company has a pipeline of three gut-restricted GI assets. The lead therapeutic candidate is MS1819, a recombinant lipase for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis and chronic pancreatitis, currently in two Phase 2 clinical trials. AzurRx is launching two clinical programs using proprietary formulations of niclosamide, a pro-inflammatory pathway inhibitor; FW-1022, for COVID-19 gastrointestinal infections and FW-420, for grade 1 Immune Checkpoint Inhibitor-Associated Colitis and diarrhea in oncology patients. The company is headquartered in Delray Beach, FL, with clinical operations in Hayward, CA. For more information, visit www.azurrx.com.