Express Oral Delivery of Biologics, Positive Phase 2 Clinical Results of Innovative Cytokine Therapy

▎WuXi AppTec Content Team Editor A few days ago, Applied Molecular Transport (AMT) announced that its oral IL-10 cytokine investigational therapy AMT-101 is a monotherapy for chronic pouchitis (a refractory inflammatory bowel disease) The Phase 2 clinical trial in patients yielded positive top-line results
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Based on a review of safety and efficacy data, an independent Data Monitoring Committee (DMC) recommended that AMT-101 be advanced to a Phase 3 clinical study at a 3 mg dose in chronic pouchitis
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Nearly 30% of ulcerative colitis (UC) patients eventually require complete colon resection
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A procedure called an ileo-anal anastomosis (IPAA) allows patients to remove waste normally after the colon and rectum have been removed
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The wall of the pouch left after surgery may then become inflamed, called pouchitis
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The clinical manifestations of pouchitis include excessive bowel movements, urgency, fecal incontinence, nocturnal exudation, and lower abdominal pain
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There are currently no approved treatments in the United States
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Acute pouchitis usually responds to antibiotic therapy, but up to 50% of patients with pouchitis develop chronic pouchitis, which frequently recurs or does not respond to antibiotic therapy
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AMT-101 is a novel gastrointestinal-selective, oral IL-10 therapy
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AMT has modified the Cholix protein secreted by Vibrio cholerae to make it a carrier for biologics to cross the intestinal epithelial barrier
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By binding to receptors on the surface of the intestinal epithelium, Cholix protein can enter the blood circulation through epithelial cells by endocytosis
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AMT-101 forms a fusion protein with IL-10 and a carrier developed based on Cholix protein, which assists IL-10 to pass through the intestinal epithelium and accumulates at the site of intestinal inflammation, potentially avoiding the possible side effects of systemic administration
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It is currently in 4 Phase 2 clinical trials for the treatment of chronic pouchitis, ulcerative colitis and rheumatoid arthritis (RA)
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▲AMT's carrier technology (Image source: AMT's official website) This double-blind phase 2 clinical trial included 22 patients with chronic pouchitis and were randomly assigned to receive 3 mg or 10 mg of oral AMT-101
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The results of the trial showed that by combining the patient data of the two dose groups, 36.
4% (8/22) of the patients had an improvement in the frequency of bowel movements
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Defecation frequency responses were observed in both dose groups as early as week 2 and persisted throughout the treatment period
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Top-line interim data showed improvement in other symptoms such as bowel urgency, urinary incontinence, and abdominal cramps
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The proportion of patients who achieved symptomatic improvement in bowel frequency in both dose groups exceeded the criteria for advancing the program into Phase 3 clinical trials
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Histologically, 22.
7% (5/22) of patients achieved a prespecified histological healing response with a Geboes score ≤3.
1, which is an objective measure of disease improvement
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The patients' median baseline Geboes score was 5.
1, indicating severe pouchitis with ulceration and tissue destruction
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Both dose groups showed histological healing responses
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▲ The key efficacy endpoint results of AMT-101 (Image source: Reference [1]) The safety and tolerability observed with AMT-101 were good
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Adverse events were mostly mild to moderate, with only one serious adverse event observed, cytomegalovirus (CMV) infection, which was determined to be unrelated to the study drug
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"We are excited to share these data with the U.
S.
FDA and other regulatory agencies to advance the development of AMT-101 in chronic pouchitis," said Bittoo Kanwar, MD, chief medical officer at AMT.
"We believe these data support AMT-101
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Potential in the treatment of mucosal immunology and inflammation-related diseases
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" Reference: [1] Applied Molecular Transport Announces Positive Top-line Phase 2 Results from FILLMORE Trial of Oral AMT-101 in Patients with Chronic Pouchitis.
Retrieved April 25, 2022 , from https://ir.
appliedmt.
com/news-releases/news-release-details/applied-molecular-transport-announces-positive-top-line-phase-2 Advances in Biomedical Health Research
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This article is for information exchange purposes only, and the views expressed in this article do not represent WuXi AppTec's position, nor do they represent WuXi AppTec's support or opposition to the views expressed in this article
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This article is also not a treatment plan recommendation
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For guidance on treatment options, please visit a regular hospital
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