Company tests drug for COVID-19-related GI infections
COVID Complications
AzurRx BioPharma, Inc. of Boca Raton, Florida, a clinical stage biopharmaceutical company specializing in the development of targeted, non-systemic therapies for gastrointestinal (GI) diseases, has begun the administration of the first dose of FW-1022 to a volunteer in the ongoing Phase 2 RESERVOIR clinical trial. FW-1022 is a proprietary oral tablet formulation of micronized niclosamide developed for the treatment of COVID-19-related GI infections. The study is targeted for completion in December 2021, and topline results from the trial are expected in March 2022.
As James Sapirstein, chief executive officer of AzurRx BioPharma, explained, “Dosing the first patient in the RESERVOIR clinical trial marks a significant milestone for AzurRx and the development of niclosamide as a potential treatment for COVID-19-related GI infections. There are currently no approved treatments available for COVID-19-related GI infections. If our development program is successful, we believe that FW-1022 could help prevent reinfection and the spread of COVID-19, as well as treat certain potentially severe complications that many people believe to be caused by the ability of SARS-CoV-2 to hide in reservoirs within the GI tract. We believe our micronized oral niclosamide therapy has the potential to target the virus directly in the gut and play an important role in treating COVID-19 patients experiencing the damaging aftereffects of COVID-19-related GI infection.”
Designed as a two-part, two-arm, placebo-controlled Phase 2 study, the RESERVOIR clinical trial’s primary goals are to confirm the safety of FW-1022 in the treatment of patients with COVID-19-related GI infections and to determine its efficacy in clearing SARS-CoV-2 from the GI tract. The primary efficacy measure of the RESERVOIR trial is the rate of fecal SARS-CoV-2 clearance (rectal swab or stool sample) assessed by RT-PCR, comparing the niclosamide arm to the placebo arm for as long as six months. These long-term observation data could demonstrate that niclosamide treatment has the potential to improve “long haul” COVID-19 symptoms.
James Pennington, M.D., chief medical officer of AzurRx, added, “Evidence continues to build in support of niclosamide as a potential COVID-19 therapy, including research from the Institut Pasteur Korea, suggesting that niclosamide could be 40 times more potent than remdesivir in inhibiting SARS-CoV-2. We believe FW-1022, our micronized formulation of niclosamide, is ideally equipped to clear SARS-CoV-2 hiding in the gut, due to its proven safety profile and known effectiveness in treating other GI ailments, and its ability to remain in the gut for long periods of time.”
Pennington continued, “It is important to understand that despite all the progress made with vaccines that they are not going to end the COVID pandemic – the disease is becoming endemic. Vaccines have given us hope, but the emergence of new and more transmissible SARS-CoV-2 variants which keep cropping up all over the world, suggest that COVID-19 may remain with us for several years to come. Moreover, we will not be able to vaccinate everyone we need to. There remains a strong need to find therapeutics that can help most of the world’s population deal with the effects of COVID-19 infections and we believe that our niclosamide therapeutic has a strong and lasting role to play in treating patients.”
Some researchers think that the GI tract is a potential 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. Currently, there is no targeted treatment for COVID GI infections, but the problem is significant.
Gastrointestinal infection symptoms, including severe diarrhea, vomiting and abdominal pain, have been reported in about 18 percent of COVID-19 cases. Of the 33 million people who are reported to have contracted COVID-19 in the U.S., that would mean that 6 million patients have had GI infection. Of the 165 million cases worldwide, there would be nearly 30 million patients. About 10 percent of patients who were infected with COVID have persistent symptoms months after their initial diagnosis. About 86 percent of these COVID “long haulers” have GI infection symptoms, with 60 percent continuing to have diarrhea months after their initial infection.
Niclosamide, a prescription small molecule drug listed as an essential medicine by the World Health Organization (WHO), has been safely used on millions of patients for other clinical indications. In the U.S., 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.
Anthelmintics are a type of medicine that kills helminths, worm-like parasites such as flukes, roundworms and tapeworms. These medicines need to be selectively toxic to the parasite and not the host. Some work by inhibiting metabolic processes that are vital to the parasite but absent or not vital in the host. Other anthelmintics are poorly absorbed through the gut, which means the parasite is exposed to much higher concentrations of the anthelmintic than the host. Starvation or paralysis or the parasite result, followed by subsequent expulsion or digestion.
AzurRx believes that there is an urgent need to develop new medicines that can be manufactured at large scale quickly to treat COVID-19. Niclosamide was recently identified as a potent inhibitor of SARS-CoV-2, the virus causing COVID-19, with potency 40 times greater than remdesivir. In addition, emerging evidence confirms the severe GI-related complications of COVID and potential fecal spread of the virus. The company hopes that its clinical trials 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. The manufacturing process for niclosamide can be scaled up to supply large populations quickly.
AzurRx 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.