DUBLIN, May 18, 2017 /PRNewswire/ --
- Study met primary endpoint demonstrating significantly
greater remission rates in patients receiving anti-MAdCAM antibody
(SHP647) compared to placebo in three
of four tested dose groups
- First study to investigate the potential role of anti-MAdCAM
antibody in the management of ulcerative colitis
(UC)
- SHP647 specifically targets a
gastrointestinal (GI) endothelial adhesion molecule known as
mucosal addressin cell adhesion molecule 1
(MAdCAM-1)
Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare
and specialty diseases, today announced publication in the
May 17, 2017 issue of The
Lancet the results from a Phase 2 study (NCT01620255)
investigating PF-00547659 (now called SHP647), an anti-mucosal addressin cell adhesion
molecule 1 (MAdCAM-1) antibody, investigated in the treatment of
moderate-to-severe ulcerative colitis in adults. Ulcerative colitis
is a chronic, relapsing and remitting inflammatory disorder of the
gastrointestinal tract that mainly affects the
colon.[1] It is not uncommon for
patients with ulcerative colitis to fail to respond to, or lose
response to, available
therapies.[2],[3]
Therefore, there is a need to develop new
therapies.[3]
In this Phase 2 study, called TURANDOT, SHP647, the first anti-MAdCAM antibody in
clinical development, met its primary endpoint demonstrating
significantly greater remission rates in patients receiving
anti-MAdCAM antibody compared to placebo in three of four tested
dose groups. Shire continues to work toward the initiation of a
pivotal Phase 3 trial for SHP647 in
the second half of 2017. The Company licensed the global rights to
all indications for PF-00547659 (SHP647) from Pfizer Inc. (NYSE: PFE) in
June 2016, adding to Shire's
established and leading gastrointestinal (GI) portfolio.
The interaction between endothelial MAdCAM-1 and α4β7 integrin
has been implicated in the pathogenesis of ulcerative
colitis.[3] SHP647 is a fully human monoclonal antibody that
directly targets MAdCAM-1, thereby blocking tissue homing of
activated α4β7 + leukocytes.[4]
"The TURANDOT trial is the first study to investigate a new
biologic, an anti-MAdCAM antibody, as a potential treatment for
ulcerative colitis, a chronic intestinal disease with high unmet
need," said Prof. Séverine Vermeire, MD, Department of
Gastroenterology, University Hospital Leuven, Belgium and TURANDOT lead investigator. "These
statistically significant results demonstrate the role that cell
adhesion plays in ulcerative colitis and suggest that inhibition of
cell adhesion mediated by MAdCAM may result in a potential
treatment for patients suffering with this disease."
"For patients with ulcerative colitis, there is a critical need
for new treatment options," said Philip
Vickers, Ph.D, Global Head of Research & Development at
Shire. "In line with Shire's commitment to researching and
developing therapeutic advances for patients with GI conditions, we
are encouraged by the statistically significant results of the
TURANDOT trial and the potential for our anti-MAdCAM antibody to
become an important therapeutic option for patients with ulcerative
colitis."
About TURANDOT
The 12-week, multicenter, double blind, placebo-controlled,
parallel-group study enrolled 357 patients with ulcerative colitis,
who failed at least one previous treatment, who were randomized to
receive SHP647 across four different
dosing groups of 7.5 mg, 22.5 mg, 75 mg, and 225 mg or placebo. The
study met the primary endpoint, which was the proportion of
patients achieving disease remission at week 12 compared to
placebo. Results showed that remission rates at week 12 were
highest in patients receiving 22.5 mg (12/72, 16.7%) and 75 mg
(11/71, 15.5%) of SHP647 and were
significantly greater than placebo in three of the four
SHP647 treatment groups. The study
also met its secondary endpoints at week 12, which included the
proportion of patients with a clinical response, and the proportion
of patients with mucosal healing in the treatment groups compared
to placebo. SHP647 appeared to be
well tolerated in this patient population. As this trial was only
12 weeks in duration, these safety data should be interpreted with
some degree of caution, a larger patient population treated for a
longer period will be needed to fully assess the safety of
SHP647 in patients with
UC.[5] See additional safety data
below.
The complete publication can be found at The
Lancet. The study results were
previously presented at Digestive Disease Week
2015.[6] Shire continues to work
toward the initiation of a pivotal Phase 3 trial for SHP647 in Q3 2017.
TURANDOT Safety Data
The frequencies of subjects with permanent or temporary
discontinuations due to treatment-emergent adverse events (TEAEs)
were low (<5%). Overall, the frequencies of serious adverse
events (SAEs) were low (5.9% of the total population). One (1)
death (due to adenocarcinoma of the colon) occurred during the
study in the SHP647 7.5 mg group,
which was considered by the data monitoring committee as unlikely
to be associated with the study drug. A larger patient population
treated for a longer period will be needed to fully assess the
safety of SHP647 in patients with
UC.
About Ulcerative Colitis
Ulcerative colitis is a chronic, idiopathic, relapsing and
remitting inflammatory disorder of the gastrointestinal tract that
mainly affects the colon.[1]
Symptoms can be debilitating and include frequent recurring
diarrhea, rectal bleeding, fever, and abdominal
pain.[7]
Ulcerative colitis is a cause of significant morbidity globally,
with incidence and prevalence continuing to increase over
time.[8] The disease can affect
people of any age; however, the peak age of onset is 30-40
years.[9]
References
- Ford AC, et al. BMJ. 2013;346:f432
- Ghosh S, et al. Ther Adv Gastroenterol.
2010;3:239-258
- Allocca M, et al. Expert Rev Clin
Immunol. 2014;10:885-95
- Pullen N, et al. Br J Pharmacol. 2009;157:281-93
- Vermeire S, et al. Lancet. 2017
http://dx.doi.org/10.1016/S0140-6736(17)30930-3
- Reinisch W, et al. Gastroenterology. 2015;148:S1193
- Ordás I, et al. Lancet. 2012;380:1606-19
- Molodecky NA, et al. Gastroenterology.
2012;142:46-54
- Cosnes J, et al. Gastroenterology. 2011;140:1785-94
NOTES TO EDITORS
About Shire
Shire is the leading global biotechnology company focused on
serving people with rare diseases and other highly specialized
conditions. We strive to develop best-in-class products, many of
which are available in more than 100 countries, across core
therapeutic areas including Hematology, Immunology, Neuroscience,
Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal /
Internal Medicine / Endocrine and Hereditary Angioedema; and a
growing franchise in Oncology.
Our employees come to work every day with a shared mission: to
develop and deliver breakthrough therapies for the hundreds of
millions of people in the world affected by rare diseases and other
high-need conditions, and who lack effective therapies to live
their lives to the fullest.
http://www.shire.com
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a further list and description of risks, uncertainties and other
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