UEG Week Virtual 2021 Congress Review - 15

UEG Week Congress Review
Oral TG2 inhibitor effective
and well tolerated in celiac
disease
A highly selective, gut-active, oral
transglutaminase 2 (TG2) inhibitor, ZED1227,
effectively prevented gluten-induced mucosal
damage in patients with celiac disease (CeD)
undergoing gluten challenge as part of a Phase
2a study.1 The study enrolled individuals with
well controlled CeD who were randomised to
receive ZED1227 10 mg (n=41), 50 mg (n=41),
or 100 mg (n=39) per day or placebo (n=38)
for 6 weeks shortly after consuming 3 grams
of gluten. The primary endpoint of the study
was attenuation of gluten-induced mucosal
damage, as measured using the ratio of villus
height to crypt depth (VH:CrD). Secondary
endpoints included intraepithelial lymphocyte
(IEL) density, TG antibodies, and patientreported
outcomes (Celiac Symptom Index
[CSI], Celiac disease questionnaire [CDQ]).
According to Detlef Schuppan, who presented
the study findings at UEG Week Virtual 2021, all
doses of ZED1227 prevented villous atrophy,
with the highest dose being the most effective.
The estimated difference from placebo in the
change in the mean VH:CrD from baseline to
Week 6 was 0.44 (95% CI: 0.15-0.73) in the
ZED1227 10 mg/day group (p=0.001), 0.49
(95% CI: 0.20-0.77) in the ZED1277 50 mg/day
group (p<0.001), and 0.48 (95% CI: 0.20-0.77)
in the ZED1227 100 mg/day group (p<0.001).
Intraepithelial lymphocyte density increased
from baseline to Week 6 in each group, however,
the increase was smallest in the 100 mg group
and greatest in the placebo group (difference
from placebo in the mean change in IED
density: -2.7 cells/100 epithelial cells in the
10 mg group, -4.2 cells/100 epithelial cells in
the 50 mg group, and -9.6 cells/100 epithelial
cells in the 100 mg group). Dose-dependent
inhibition of TG-2 autoantibody increases and
normalisation of extra-intestinal (hepatic)
inflammation were also observed. ZED1227
100 mg/day stabilised symptoms and quality of
life compared with the other treatment arms.
ZED1227 was well tolerated, with a similar
safety profile to placebo. Rash developed in
three patients (8%) in the ZED1227 100 mg/day
treatment group.
" This is a very specific drug acting on a key
mechanism unique to CeD pathogenesis, "
said Detlef Schuppan. " It is currently the
only pharmacological therapy with clear
histological and clinical efficacy. " A Phase 2b/3
study in patients with mucosal damage and
symptoms despite a gluten-free diet will be
initiated towards the end of 2021.
1. Schuppan D, et al. N Engl J Med 2021;385(1):35-45.
15
Helena Cortez-Pinto, UEG Vice President
Mixed-donor FMT leads to weight loss in subset
of obese individuals
Mixed-donor faecal microbiota transplantation (FMT) leads to significant weight
loss in a subset of individuals with obesity, and this weight loss may be associated
with changes in the gut-dwelling bacterial species, Bacteroides dorei (B. dorei).
These were the main findings from a study conducted by researchers from the
Chinese University of Hong Kong, who aimed to determine the effectiveness of
intensive FMT on weight loss in obese individuals (median BMI of 32 kg/m2),
to evaluate the impact of single- or mixed-donor FMT on the recipients' gut
microbiota, and to identify bacteria taxonomic and clinical factors associated with
weight loss after FMT in obese individuals. Two separate studies were performed: in
the first, 38 individuals received non-intensive mixed-donor FMT (nFMT) infusions
once per month for four months, while in the second, nine individuals received
single-donor intensive FMT (iFMT) for 5 days per week for 4 weeks. All study
participants were followed for 52 weeks.
No significant differences in weight changes over 12 months were observed between
the two FMT groups, although 5/38 nFMT recipients (13.2%) had achieved ≥10%
weight loss at the 6- or 12-month follow-up. Intensive FMT led to transient increases
in donor-derived species during FMT, greater changes in the bacterial composition
during FMT, and a closer resemblance to the donor microbiome profiles during FMT
and at first follow-up than nFMT, however, the researchers concluded that there
were no durable differences between iFMT and nFMT in terms of weight loss or gut
microbiota composition.
Mixed-donor FMT, but not single-donor FMT, was associated with a significantly
increased abundance of butyrate-producing bacteria (e.g. Roseburia, Eubacterium,
Faecalibacteria spp.) (p<0.01). A high baseline abundance of B. dorei and a greater
reduction following FMT was associated with weight loss >10% after FMT.
" We believe that these findings will be of value in the design of personalised
microbial-based therapies for obesity based on donor and recipient selection " ,
concluded Zhilu Xu, who presented the study results.
https://www.ueg.eu/library/oral-inhibitor-of-tissue-transglutaminase-prevents-mucosal-damage-in-celiac-patients-undergoing-gluten-challenge/248279 https://www.ueg.eu/library/recipient-s-gut-bacteria-composition-predicts-efficacy-of-fecal-microbiota-transplantation-in-inducing-weight-loss-in-obese-subjects/248507
UEG Week Virtual 2021 Congress Review

Table of Contents for the Digital Edition of UEG Week Virtual 2021 Congress Review
