Pharma News: Azurrx Biopharma’s Proprietary Niclosamide Formulations To Treat COVID-19 Gastrointestinal Infections

Pharma News: Florida based AzurRx BioPharma, a company specializing in the development of non-systemic therapies for gastrointestinal (GI) diseases has announced that it has signed an exclusive worldwide licensing agreement with First Wave Bio, Inc for the use of their patented and proprietary oral and rectal formulations of niclosamide for the treatment of immune checkpoint inhibitor-associated colitis (ICI-AC) and COVID-19 GI infections.

The drug niclosamide is a small molecule drug that was approved by the FDA in 1982 for the treatment of intestinal tapeworm infections and is on the World Health Organization’s (WHO) list of essential medicines. It has been safely used by millions of patients and is being investigated as a potential new therapy for inflammatory diseases and viral infections.
 
Established in 2015, First Wave has invested in translational biology along with process development and manufacturing to develop proprietary oral and rectal gut-targeted formulations of niclosamide for the treatment of ICI-AC, COVID-19 GI-infections, and inflammatory bowel disease (IBD).
 
Dr James Sapirstein, President and Chief Executive Officer of AzurRx told Thailand Medical News, “The acquisition of rights to niclosamide for these indications gives us an opportunity to strategically expand our existing pipeline and pursue multiple GI indications in the oncology and infectious disease arenas. We are impressed with First Wave’s Phase 1b/2a clinical data, strong IP and patent position, and the significant unmet medical needs and market opportunities addressed by these two assets. We believe these niclosamide formulations could offer significant advantages over other currently available treatments. They are not systemically absorbed, potentially allowing for higher local GI concentrations of drug delivery and avoiding steroid-related immunosuppressant complications.”
 
Dr Sapirstein added, “With these new assets, combined with our current pipeline, we believe 2021 will be a very exciting and transformational year for AzurRx. AzurRx is on track to report top-line data for its two Phase 2 MS1819 clinical trials in the first and second quarters of 2021 and anticipates initiating both the Phase 2 COVID-19 GI Infection trial and a Phase 1b/2a ICI-AC trial in the first half of 2021.”
 
Co-Founder and Chief Executive Officer of First Wave Bio, Gary D. Glick, Ph.D.,  added, “The license of our niclosamide technology for the immune checkpoint inhibitor and COVID indications is a significant milestone for our company and we are very pleased to have found a clinical and commercial development partner in AzurRx. We look forward to working with the AzurRx team to take our novel niclosamide therapies to the clinic in 2021 and to rapidly bringing these therapies to cancer and COVID-19 patients.”
 
With the new agreement, AzurRx is granted a worldwide, exclusive right to develop, manufacture, and commercialize First Wave’s proprietary immediate release oral and enema formulations of niclosamide for the treatment of ICI-AC and COVID-19 GI infections.
 
First Wave will receive an upfront payment of US$10.25 million in cash payable US$9.0 million at closing and US$1.25 million by June 30, 2021 and US$3.0 million of Convertible Junior Preferred Stock, which shall be convertible into common stock following shareholder approval, and up to US$74.0 million in potential development and commercial milestones, as well as mid single-digit royalties on product sales for the ICI-AC and COVID-19 GI indications.
 
COVID-19 Gastrointestinal Infections
Gastrointestinal infection symptoms (severe diarrhea, vomiting and abdominal pain) have been reported in about 18% of COVID-19 cases. Of the 19 million individuals who are reported to have contracted COVID-19 in the United States, this would translate into 3.4 million patients having GI infection. Of the 81 million cases globally, it would be 15 million.
 
As of date, 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.
 
Immune Checkpoint Inhibitor-Associated Colitis and Diarrhea
ICIs or Immune checkpoint inhibitors are monoclonal antibodies that target down-regulators of the anti-cancer immune response and have revolutionized the treatment of a variety of malignancies. However, many immune-related adverse events, especially diarrhea and colitis, limit their use. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and whether they are used in combination used in combination.
 
Roughly 44% of patients with advanced and metastatic cancer tumors (~260,000 patients) are eligible to receive immune checkpoint inhibitors (ICIs). Approximately 30% of ICI patients develop diarrhea, which can progress to colitis. The onset of diarrhea in ICI-AC patients occurs within 6-7 weeks and progressively worsens, and the progression to colitis is rapid and unpredictable. For example, in patients taking ipilimumab (Yervoy), between 25-30% of patients developed diarrhea and ~8-12% developed colitis.2 Moreover, the trend is towards the use of combination ICI therapies (e.g. Yervoy and Opdivo) and this will lead to a concomitant increase in both diarrhea and colitis.
 
The administration of corticosteroids, or treatment with certain immunosuppressive biologics, while withholding ICI therapy are recommended for grade 2 or more severe colitis (National Cancer Institute 2020). The impact of this colitis complication and treatment may reduce the goal of progression free cancer survival. An oral, non-absorbed treatment, such as niclosamide, for grade 1 colitis (diarrhea) may prevent progression to grade 2 disease. There currently is no approved treatment for grade 1 colitis.
 
Thailand Medical News has already published a few past studies showing the effectiveness of niclosamide to treat COVID-19 infections but it it is now emerging that niclosamide is more effective in treating specifically COVID-19 related Gastrointestinal infections. https://www.thailandmedical.news/news/covid-19-drugs-niclosamide-emerging-as-another-potential-repurposed-drug-candidate-to-treat-covid-19-
 
https://www.thailandmedical.news/news/niclosamide-shows-efficacy-against-covid-19-in-animal-tests-according-to-south-korean-pharmaceutical-giant-daewoong
 
https://aac.asm.org/content/64/7/e00819-20
 
There are also ongoing clinical trials at the moment testing the efficacy of niclosamide to treat COVID-19 https://clinicaltrials.gov/ct2/show/NCT04603924
 
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