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Celiac.com 09/21/2022 - The dream of creating a safe, effective drug that can help people with celiac disease to tolerate small amounts, or perhaps even large amounts, of gluten. Until its recent failure, 9 Meters' larazotide was the only celiac drug in Phase 3 clinical trials. The recent discontinuation of larazotide, based on disappointing interim results, highlights the unmet need for effective alternatives to a gluten-free diet for treating celiac disease. Larazotide's failure also opens the doors for current and future Phase 1 and Phase 2 celiac therapies to be first-to-market. It also highlights the lack of a good lineup of potential new drugs. The reality is that, with the collapse of several once promising candidates, the bench for viable alternative celiac disease treatments is shallow, at best. Current Celiac Disease Pipeline Therapies Include: Latiglutenase (ImmunogenX) PRV-015 (Provention Bio, Inc. with Amgen) TAK-101 (Takeda Pharmaceuticals) ZED-1227 (ZEDIRA GmbH) KAN-101 (Anokion SA) In an effort to assess the current and future alternatives for treating celiac disease without a gluten-free diet, data marketing company Spherix recently interviewed one-hundred US gastroenterologists, and conducted eight qualitative interviews to compile a report on the issue. Spherix has issued a recent report on the form gastroenterologists engaged in a thorough review of these pipeline product descriptions (based on publicly available clinical information for each product). The report assesses celiac diagnostic and treatment trends emerging, as well as physician reactions to potential therapies in the pipeline. The 2022 report reveals a greater sense of urgency from gastroenterologists versus the 2021 report. Indeed, the number of respondents in the 2022 survey who say that their celiac patient load has increased in the past year, is up by 60% over 2021. Read more at PRNewswire.com

Celiac.com 07/18/2022 - Currently, a gluten-free diet is the only treatment for people with celiac disease. A number of companies have been attempting to create treatments that reduce or eliminate celiac disease symptoms, mostly for patients on a gluten-free diet. Larazotide, whose clinical trial is dubbed "CedLara," is such a drug. It's designed to reduce persistent celiac disease symptoms for people on a gluten-free diet. In an earlier phase 2 trial, Larazotide was shown to reduce celiac symptoms in patients who had been on a gluten-free diet for at least 12 months. Many were excited to see how it would do in a phase 3 trial. The answer, unless we get some better news from 9 Meters Biopharma, the company that has been developing it, is badly. For the phase 3 trial, 9 Meters Biopharma set out to enroll 525 patients in the phase 3 trial to determine the effect of larazotide on celiac disease severity. To determine the number of people needed to measure a statistically significant effect, the company conducted an analysis with half of the expected patients enrolled. According to a company news release, their analysis showed that the additional number of patients needed to produce a significant clinical outcome between placebo and Larazotide is too large for the company to pursue. Reading between the lines of the news release, it seems as though the the company might need far more test subject than originally estimated to show a statistically significant result. That means that, no matter how effective the drug was for some people, the company can't afford to test in large enough numbers to show that it's genuinely effective. With the failure of Larazotide, 9 Meters Biopharma announced that it will be pivoting to the development of vurolenatide, a repeated injection aimed at increasing nutrient absorption in patients with short bowel syndrome. Phase 2 results should be unveiled soon. The failure of Larazotide marks the latest addition to the growing graveyard of celiac disease drugs. As Larazotide has been touted since 2013, this failure is particularly disappointing. To punctuate the ignoble end for a once hopeful drug, the company's CEO and president, John Temperato, says that financial and human resources from Larazotide will be reassigned to advance vurolenatide and the company’s early-stage product candidates, pending a review. Read more at seekingalpha.com

Celiac.com 06/16/2021 - Weeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called Multisystem Inflammatory Syndrome in Children (MIS-C). A new study offers hope for diagnosis, treatment and prevention of MIS-C. Gastrointestinal symptoms are common in MIS-C patients and severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not previously been identified. A team of researchers recently set out to learn more about diagnosing, treating, and preventing MIS-C. The research team analyzed specimens from 19 children with MIS-C, 26 with acute COVID-19, and 55 control subjects and assessed stool samples for SARS-CoV-2 by RT-PCR, and plasma samples for markers of breakdown of mucosal barrier integrity, including zonulin. They used ultra-sensitive antigen detection to probe for SARS-CoV-2 antigenemia in plasma, and then characterized the resulting immune responses. As proof of concept, we treated a MIS-C patient with larazotide, a zonulin antagonist, and monitored impact on antigenemia and clinical response. The team demonstrated that, in MIS-C patients, prolonged presence of SARS-CoV-2 in the GI tract leads to the release of zonulin, an intestinal permeability biomarker, which causes SARS-CoV-2 antigens to flow into the bloodstream, and triggers hyperinflammation. The one MIS-C patient treated with larazotide, a drug which is currently in clinical trials as a possible treatment for celiac disease, showed a coinciding decrease in plasma SARS-CoV-2 Spike antigen levels, inflammatory markers, along with clinical improvement above that resulted from presently available treatments. The team's data detailing the pathogenesis of MIS-C offers insight into targets for diagnosing, treating, and preventing MIS-C, which are crucial to addressing this increasingly common severe COVID-19-related disease in children. Read more at The Journal of Clinical Investigation. The research team included Lael M. Yonker, Tal Gilboa, Alana F. Ogata, Yasmeen Senussi, Roey Lazarovits, Brittany P. Boribong, Yannic C. Bartsch, Maggie Loiselle, Magali Noval Rivas,4 Rebecca A. Porritt,4 Rosiane Lima,1 Jameson P. Davis, Eva J. Farkas, Madeleine D. Burns, Nicola Young, Vinay S. Mahajan, Soroush Hajizadeh, Xcanda I. Herrera Lopez,5 Johannes Kreuzer, Robert Morris, Enid E. Martinez, Isaac Han, Kettner Griswold Jr., Nicholas C. Barry, David B. Thompson, George Church, Andrea G. Edlow, Wilhelm Haas, Shiv Pillai, Moshe Arditi, Galit Alter, David R. Walt, and Alessio Fasano. They are variously affiliated with the Department of Pediatrics, Massachusetts General Hospital, Boston, United States of America; the Department of Pathology, Brigham and Women’s Hospital, Boston, United States of America; the Department of Medicine, Ragon Institute of MGH, MIT and Harvard, Cambridge, United States of America; the Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, United States of America; the Department of Medicine, Massachusetts General Hospital, Boston, United States of America; the Department of Immunology, Wyss Institute for Biologically Inspired Engineering, Boston, United States of America; the Department of Genetics, Harvard Medical School, Boston, United States of America; the Department of Obstetrics, Gynecology, and Reproductive Biology, Massachusetts General Hospital, Boston, United States of America; the Massachusetts General Hospital, Boston, United States of America; the Department of Immunology, Massachusetts General Hospital, Boston, United States of America; and the Department of Pathology, Harvard Medical School, Boston, United States of America.

Celiac.com 12/20/2018 - Intestinal permeability is thought to play a key role in the translocation of bacteria that lead to nonalcoholic fatty liver disease (NAFLD), a disorder in which fat accumulates in the liver. Intestinal permeability is also thought to play a significant role in the development of Nonalcoholic steatohepatitis (NASH). In a new preclinical study, a team of researchers affiliated with Innovate Biopharmaceuticals recently assessed the effects of larazotide acetate on intestinal permeability. Their data from that study show that larazotide has a marked effect on intestinal permeability. The company expects to see more data detailing the use of larazotide in combination with approved drugs liraglutide (VICTOZA®) and obeticholic acid (OCALIVA®), in development for treatment of NASH, by early 2019. Based on larazotide's ability to re-normalize intestinal permeability, the parent company plans to launch clinical development program targeted at NASH in 2019. In the most recent study, researchers evaluated the effects of larazotide in a model of NASH that develops from consumption of a specified diet, the DIAMONDTM mouse model. The pre-clinical model confirms NAFLD/NASH in response to a high fat, high sugar Western diet, including insulin resistance, obesity, which mirrors human disease progression and histopathology. As tested, larazotide triggered a clear reduction in gut barrier permeability, a known pathological abnormality in chronic liver diseases, specifically NASH. Any drug that can prevent or reduce gut permeability could be helpful in treating NASH. The company plans to share the complete NASH pre-clinical results for publication in 2019. According to Dr. Arun Sanyal, Professor and Chair, Division of Gastroenterology, Hepatology and Nutrition at the Virginia Commonwealth University (VCU) School of Medicine, "Increased intestinal permeability has been linked to many aspects of metabolic syndrome including type 2 diabetes and nonalcoholic fatty liver disease. The demonstration of reduced gut permeability with larazotide in the setting of diet-induced obesity opens up the possibility of modulating the outcomes of metabolic syndrome, including NASH, via this mechanism and warrants further development for these indications." Obviously, any drug that can reduce gut permeability could also have implications for the treatment of celiac disease. Look for celiac.com to bring you more news on efforts to develop treatments for NASH, NAFLD, and related conditions, as information becomes available. Read more at: Nasdaq.com