First pharmacological therapy with clear efficacy in coeliac disease patients

The administration of ZED-1227 demonstrated clinical and histological efficacy in patients with coeliac disease. This is the first pharmacological therapy for coeliac disease patients that showed efficacy in a phase 2a trial. Moreover, no important side effects were reported. A phase 2b/3 trial will be conducted among symptomatic coeliac disease patients at the end of this year to investigate the full potential of the new agent.

A gluten-free diet is the most important therapy for coeliac disease patients. Beyond the psychological and social burden of maintaining a strict gluten-free diet, minimal gluten intake cannot be avoided. Minimal ingestion of gluten can already cause symptoms in 30% of the patients, according to Prof. Detlef Schuppan (Mainz University Medical Center, Germany). Therefore, a supportive pharmacological therapy is needed. Currently there is no effective or approved drug for coeliac disease. A phase 2a trial examined ZED-1227, an irreversible transglutaminase-2 inhibitor, among 160 coeliac patients in remission who followed a gluten-free diet [1]. All patients were to eat a standardised cookie with 3 g gluten daily for 6 weeks and were randomised to 10 mg, 50 mg, or 100 mg of ZED-1227 (oral, once daily), or placebo. Primary endpoint was histological damage, represented by villus height to crypt depth ratio.

Patients in all ZED-1227 conditions showed significantly improved villus height to crypt depth ratios compared with patients receiving placebo (P<0.001). Similarly, the intraepithelial lymphocyte (IEL) density was significantly lower in the ZED-1227 groups, compared with placebo. Other secondary endpoints, such as the Celiac Disease Questionnaire Gastrointestinal (CDQ GI) symptom subscore, transglutaminase-2 autoantibodies, and markers of inflammation showed patient benefits for the ZED-1227 subjects. To conclude, no relevant side effects were reported in this trial.

1. Schuppan D, et al. Oral inhibitor of transglutaminase 2 prevents mucosal damage in coeliac patients undergoing gluten challenge. LB06, UEG Week 2021 Virtual Congress, 03–05 October.

 

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Posted on 27 October, 2021