Department of Gastroenterology & Hepatology, University Hospital Zurich, Zurich, Switzerland.
Immunotherapy. 2017 Nov;9(14):1143-1152. doi: 10.2217/imt-2017-0085. Epub 2017 Sep 18.
Alicaforsen is a 20-base antisense oligonucleotide inhibiting ICAM-1 production, which is an important adhesion molecule involved in leukocyte migration and trafficking to the site of inflammation. Hitherto, alicaforsen has been granted orphan drug designation and is prescribed as an unlicensed medicine in accordance with international regulation for the treatment of pouchitis and left-sided ulcerative colitis. Given the positive results evolving from one open-label trial and one case series in patients with chronic refractory pouchitis, US FDA has agreed to a rolling submission for a license application for the treatment of pouchitis, which has been recently initiated. Whether alicaforsen leads to higher endoscopic and clinical remission rates as placebo and whether the response can be maintained in the long-term in larger studies is yet unknown. An ongoing multicenter international Phase III trial will definitely address these unanswered questions.
阿利卡福森是一种 20 碱基反义寡核苷酸，能抑制细胞间黏附分子-1（ICAM-1）的产生，后者是一种重要的黏附分子，参与白细胞向炎症部位的迁移和运输。迄今为止，阿利卡福森已被授予孤儿药资格，并根据国际规定，作为未经许可的药物用于治疗 pouchitis 和左侧溃疡性结肠炎。鉴于一项开放性试验和一项慢性难治性 pouchitis 患者的病例系列研究取得了积极结果，美国食品和药物管理局已同意对 pouchitis 的许可申请进行滚动提交，该申请最近已启动。阿利卡福森是否能像安慰剂一样提高内镜和临床缓解率，以及在更大规模的研究中能否长期维持这种反应，目前尚不清楚。一项正在进行的多中心国际 III 期试验肯定会解决这些悬而未决的问题。
