The Liver Meeting

The Liver Meeting

Issue: January 2022
Source:

Sanyal AJ. PROXYMO demonstrates safety and efficacy of cotadutide, a novel incretin co-agonist in biopsy-proven non-cirrhotic NASH with fibrosis. Presented at: The Liver Meeting Digital Experience; Nov. 12-15, 2021 (virtual meeting).

Disclosures: Sanyal reports financial relationships with Axcella Health, 89Bio, Affyimmune, Albireo, Akarna, Allergan, Amra, Ardelyx, Astra Zeneca, BASF, Bird Rock, Boehringer Ingelheim, Bristol Myers, Chemomab, Cirius, Conatus, Cumberland, Durect, ENYO, Echosens, Elsevier, Exhalenz, Fractyl, Galectin, Galmed, Genentech, General Electric, Genfit, Gilead, HemoShear, Immuron, IFMO, Indalo, Innovate, Intercept, Inventiva, Janssen, Karius, Lilly, Lipocine, Madrigal, Mallinckrodt, Merck, NGM Bio, Nimbus, Nitto Denko, NorthSea Therapeutics, Novartis, Novo Nordisk, OWL, Perspectum, Pfizer, Poxel, Redx, Sagimet, Salix, Sanofi, Sanyal Bio, Sequana, Servier, Second Genome, Sunrise, Takeda, Terns, Teva, Thera technologies, Tiziana, UpToDate and Zydus.
November 17, 2021
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Novel incretin co-agonist improves disease activity in noncirrhotic NASH

Issue: January 2022
Source:

Sanyal AJ. PROXYMO demonstrates safety and efficacy of cotadutide, a novel incretin co-agonist in biopsy-proven non-cirrhotic NASH with fibrosis. Presented at: The Liver Meeting Digital Experience; Nov. 12-15, 2021 (virtual meeting).

Disclosures: Sanyal reports financial relationships with Axcella Health, 89Bio, Affyimmune, Albireo, Akarna, Allergan, Amra, Ardelyx, Astra Zeneca, BASF, Bird Rock, Boehringer Ingelheim, Bristol Myers, Chemomab, Cirius, Conatus, Cumberland, Durect, ENYO, Echosens, Elsevier, Exhalenz, Fractyl, Galectin, Galmed, Genentech, General Electric, Genfit, Gilead, HemoShear, Immuron, IFMO, Indalo, Innovate, Intercept, Inventiva, Janssen, Karius, Lilly, Lipocine, Madrigal, Mallinckrodt, Merck, NGM Bio, Nimbus, Nitto Denko, NorthSea Therapeutics, Novartis, Novo Nordisk, OWL, Perspectum, Pfizer, Poxel, Redx, Sagimet, Salix, Sanofi, Sanyal Bio, Sequana, Servier, Second Genome, Sunrise, Takeda, Terns, Teva, Thera technologies, Tiziana, UpToDate and Zydus.
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Cotadutide was safe and effective in improving markers of disease activity and fibrosis among patients with biopsy-proven noncirrhotic nonalcoholic steatohepatitis, according to research presented at The Liver Meeting Digital Experience.

“While many agents [for NASH] are under development, none are approved and current drugs in development also have specific limitations, providing a rationale for further drug development for NASH,” Arun J. Sanyal, MBBS, MD, professor in the department of internal medicine in the division of gastroenterology, hepatology and nutrition at Virginia Commonwealth University School of Medicine, said. “MEDI0382, cotadutide (cota), is a novel oxyntomodulin-like single peptide with dual activity at GLP-1 and glucagon receptors. By having this dual activity and oxyntomodulin-like profile, it is differentiated from GLP-1s alone as shown in this preclinical animal model where cota produced greater improvement in steatosis, inflammation and ballooning as well as improvement in some circulating biomarkers of fibrosis. This was the basis for fast-track designation from the FDA.”

Compared with placebo, cotadutide 600 µg induced robust mean reductions in Absolute hepatic fat fraction; –6.2% Relative hepatic fat fraction; –30.6%

The PROXYMO study was a double-blind, placebo-controlled study where researchers subcutaneously dosed 74 patients once-daily with either cota 300 µg, cota 600 µg or placebo (all groups, n = 24). All patients had biopsy-proven non-cirrhotic NASH with fibrosis with and without type 2 diabetes and hepatic fat fraction (HFF) greater than 10%. Researchers monitored patients for safety and hepatic steatosis compared with placebo. Biomarker evaluation occurred at baseline, end-of-treatment and consecutively throughout the trial.

Compared with baseline, treatment with cota yielded dose-dependent and time-dependent treatment effects within both dosage groups at week 19. Within the cota 600 µg group specifically, researchers noted robust mean reductions in absolute HFF (–6.2%; 95% CI, –10.5 to –1.84), relative HFF (–30.6%; 95% CI, –55.8 to –5.4), alanine transaminase (–26.2 IU/L; 95% CI, – 50.4 to – 2.1) and aspartate transaminase (–16.9 IU/L; 95% CI, –33.2 to –0.8) compared with placebo. Treatment with cota was safe and well-tolerated with the majority of adverse events of mild to moderate severity.

Arun Sanyal

“PROXYMO demonstrated safety and efficacy of cotadutide in patients with biopsy-proven NASH,” Sanyal concluded. “These data provide support for further evaluation of cotadutide for this indication in target populations; this is the first demonstration of the effects of a GLP-1 glucagon co-agonist in NASH.