AzurRx BioPharma Engages PPD to Manage Clinical Trial for Niclosamide as Treatment for Grade 1 Immune Checkpoint Inhibitor-Associated Colitis

AzurRx BioPharma, Inc. recently announced it has entered into an agreement with PPD, Inc. for its planned Phase 1b/2a clinical trial evaluating proprietary formulations of micronized niclosamide for grade 1 colitis and diarrhea in oncology patients receiving treatment with immune checkpoint inhibitors (ICIs).

Under the terms of the agreement, PPD will manage the Phase 1b/2a clinical trial using both oral immediate-release tablet and topical rectal enema foam formulations of micronized oral niclosamide, also known as FW-420. AzurRx anticipates initiating the trial during the second quarter of 2021.

“The goal of our FW-420 clinical program is to develop a safe, effective, and non-systemic treatment for immune checkpoint inhibitor-associated colitis, and we are excited to once again partner with PPD to begin the preparations for our Phase 1b/2a clinical trial,” said James Sapirstein, President and CEO of AzurRx BioPharma. “The development of immune checkpoint inhibitors has marked a major advance in cancer therapeutics, but the drugs can induce a serious inflammation of the bowels, which if left unchecked, can prove life-threatening and force patients to halt treatment. There are currently no treatments available for grade 1 colitis resulting from the use of ICIs. We believe an oral, non-absorbed treatment, such as FW-420, could prevent the condition from progressing and enable patients to continue their treatment regimen uninterrupted. We hope to rapidly advance the FW-420 program with the support of PPD.”

The agreement with PPD marks the second clinical trial involving niclosamide that the CRO will manage for AzurRx. As previously announced, PPD is also managing AzurRx’s Phase 2 clinical trial to investigate niclosamide as a treatment for COVID-19-related gastrointestinal infections, planned for the second quarter of 2021.

Daniel Burch, MD, Senior Vice President and Global Head of PPD Biotech, stated “We are pleased to have this opportunity to broaden our collaboration with AzurRx as it expands its clinical program for niclosamide to bring relief to patients suffering from immune checkpoint inhibitor-associated colitis. We look forward to utilizing our expertise and capabilities to advance the development of FW-420, beginning with the upcoming clinical trial.”

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response and have revolutionized the treatment of a variety of malignancies. The global market for ICIs is significant; it was over $22 billion in 2019 and growing rapidly. Approximately 44% of patients with advanced cancer tumors (more than 260,000 patients) are eligible to receive immune checkpoint inhibitors. 

However, many immune-related adverse events, especially diarrhea and colitis, limit their use. The incidence of immune-mediated colitis (IMC) ranges from 1% to 25% depending on the type of ICI and whether they are used in combination used in combination. 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% and 30% of patients developed diarrhea and roughly 8% to 12% developed colitis.³ Moreover, the trend is towards the use of combination ICI therapies (eg, Yervoy and Opdivo) and this will lead to a concomitant increase in both diarrhea and colitis.

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.

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 US 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.

FW-420 is a niclosamide-based small molecule anti-inflammatory inhibitor therapy for the treatment of immune checkpoint inhibitor-associated colitis (ICI-AC) and diarrhea in metastatic cancer patients.  FW-420 will be supplied in two formulations, as an oral immediate-release tablet and as a topical rectal enema foam. The standard care for treating inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s Disease, corticosteroids and 5-ASAs, can cause problems when used for check point inhibitor patients due to their immunosuppressant effects. FW-420 has the potential to safely treat grade 1 ICI-associated colitis and diarrhea and prevent its progression to more serious and potentially fatal later stages. The overall goal of early niclosamide treatment is to enable oncology patients to remain on, or spend minimal time off, their ICI treatment programs without interruption.

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. AzurRx is also advancing 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, Florida with clinical operations in Hayward, California. For more information, visit www.azurrx.com.

PPD is a leading global contract research organization providing comprehensive, integrated drug development, laboratory and lifecycle management services. Our customers include pharmaceutical, biotechnology, medical device, academic and government organizations. With offices in 47 countries and more than 26,000 professionals worldwide, PPD applies innovative technologies, therapeutic expertise and a firm commitment to quality to help customers bend the cost and time curve of drug development and optimize value in delivering life-changing therapies to improve health. For more information, visit www.ppd.com.