Abstract
Carotegrast methyl (Carogra®) is a small-molecule α4 integrin antagonist being developed by EA Pharma (formerly Ajinomoto Pharmaceuticals) and Kissei Pharmaceutical for the treatment of ulcerative colitis. The active metabolite of carotegrast methyl exerts an anti-inflammatory effect by blocking the interaction of α4β1 or α4β7 integrins and their ligands, VCAM-1 and MAd-CAM-1, thereby inhibiting the adhesion of inflammatory cells, including T cells, to vascular endothelial cells and extravasation into inflammatory sites. In March 2022, carotegrast methyl received its first approval in Japan for the treatment of moderate ulcerative colitis in patients who had inadequate response to 5-aminosalicylic acid. This article summarizes the milestones in the development of carotegrast methyl leading to this first approval for the treatment of moderate ulcerative colitis.
Similar content being viewed by others
References
Gubatan J, Keyashian K, Rubin SJS, et al. Anti-integrins for the treatment of inflammatory bowel disease: current evidence and perspectives. Clin Exp Gastroenterol. 2021;14:333–42.
Pérez-Jeldres T, Tyler CJ, Boyer JD, et al. Cell trafficking interference in inflammatory bowel disease: therapeutic interventions based on basic pathogenesis concepts. Inflamm Bowel Dis. 2019;25(2):270–82.
EA Pharma Co., Ltd., Kissei Pharmaceutical Co., Ltd. CAROGRA® tablets, approved in Japan for treatment of ulcerative colitis: the world-first orally available α4 integrin antagonist [media release]. https://www.eapharma.co.jp/en/news/2022/0328_2.html. Accessed 28 Mar 2022
EA Pharma Co., Ltd. Carogra (carotegrast methyl): Japanese prescribing information. 2022. https://www.pmda.go.jp/PmdaSearch/iyakuDetail/111890_23990A7F1020_1_02. Accessed 14 Apr 2022.
Ajinomoto Pharmaceuticals Co., Ltd., Kissei Pharmaceutical Co., Ltd. Kissei and Ajinomoto Pharmaceuticals announce partnership for joint development and marketing of AJM300 and AJG511 for treatment of ulcerative colitis in Japan [media release]. https://www.eapharma.co.jp/en/news/2015/0331.html. Accessed 31 Mar 2015
EA Pharma Co., Ltd., Kissei Pharmacetuicals Co., Ltd. Change of marketing scheme for "RECTABUL® 2 mg Rectal Foam 14 Doses" and AJM300 (nonproprietary name: carotegrast methyl), both for treatment of ulcerative colitis: agreement concluded [media release]. https://www.eapharma.co.jp/en/news/2021/1115.html. Accessed 15 Nov 2021
Sugiura T, Kageyama S, Andou A, et al. Oral treatment with a novel small molecule alpha 4 integrin antagonist, AJM300, prevents the development of experimental colitis in mice. J Crohns Colitis. 2013;7(11):e533–42.
Fukase H, Kajioka T, Oikawa I, et al. AJM300, a novel oral antagonist of α4-integrin, sustains an increase in circulating lymphocytes: a randomised controlled trial in healthy male subjects. Br J Clin Pharmacol. 2020;86(3):591–600.
Fukase H, Kajioka T, Oikawa I, et al. Food effect on a single high dose of carotegrast methyl, an oral antagonist of α4-integrin, in healthy male subjects: a randomised, placebo-controlled, double-blind study. Clin Drug Investig. 2020;40(3):237–47.
Matsuoka K, Watanabe M, Ohmori T, et al. AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Gastroenterol Hepatol. 2022. https://doi.org/10.1016/s2468-1253(22)00022-x.
Yoshimura N, Watanabe M, Motoya S, et al. Safety and efficacy of AJM300, an oral antagonist of α4 Integrin, in induction therapy for patients with active ulcerative colitis. Gastroenterology. 2015;149(7):1775-83.e2.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The preparation of this review was not supported by any external funding.
Authorship and Conflict of interest
During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Sohita Dhillon is a contracted employee of Adis International Ltd/Springer Nature and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.
Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability
Not applicable.
Additional information
This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Dhillon, S. Carotegrast Methyl: First Approval. Drugs 82, 1011–1016 (2022). https://doi.org/10.1007/s40265-022-01732-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40265-022-01732-0