52-week results of the Phase 3 ADMIRE-CD trial presented at the
12th Congress of the European Crohn’s and Colitis Organisation
(ECCO)
Takeda Pharmaceutical Company Limited (TSE:4502) (“Takeda”) and
TiGenix NV (Euronext Brussels and Nasdaq:TIG) (“TiGenix”) today
announced new data from the Phase 3 ADMIRE-CD clinical trial, which
indicated that investigational compound Cx601, a suspension of
allogeneic expanded adipose-derived stem cells (eASC), maintained
long-term remission of treatment refractory complex perianal
fistulas in patients with Crohn’s disease over 52 weeks.1 Results
were presented at the 12th Congress of the European Crohn’s and
Colitis Organisation (ECCO).
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The ADMIRE-CD trial is a randomized, double-blind, controlled,
Phase 3 trial, designed to investigate the efficacy and safety of
the investigational compound Cx601 for the treatment of complex
perianal fistulas in patients with Crohn’s disease.2 Patients were
randomized to a single administration of Cx601 cells or placebo
(control), both added to standard of care.1 A significantly greater
proportion of patients in the Cx601 group versus the control group
achieved clinical and radiological combined remission* (56.3% and
38.6%; p=0.010), and clinical remission (59.2% and 41.6%; p=0.013)
at week 52 in the modified intention-to-treat population (mITT).1
Of those mITT patients who had shown combined remission at week 24,
a greater number in the Cx601 group versus the control group
reported no relapse at week 52 (75.0% and 55.9%).1 The rates and
types of treatment related adverse events (non-serious and serious)
and discontinuations due to adverse events were indicated to be
similar in both groups (Cx601: 20.4%; control: 26.5%).1
Crohn’s disease is a chronic inflammatory disease of the
gastrointestinal tract, which is thought to affect up to 1.6
million people in Europe.3 Complex perianal fistulas are a
complication for people living with Crohn’s disease and there are
limited treatment options. Recognizing the rare and debilitating
nature of the disorder, and lack of treatment options, in 2009 the
European Commission granted Cx601 orphan designation for the
treatment of anal fistula. In March 2016, TiGenix announced that it
submitted the Marketing Authorization Application (MAA) to the
European Medicines Agency (EMA) for Cx601, and a decision by the
EMA is expected in 2017. Additionally, in September 2016 orphan
drug status was received from the Swiss Agency for Therapeutic
Products (Swissmedic) regarding Cx601 for the rare disease complex
perianal fistulas in Crohn’s disease.4
“Perianal fistulizing Crohn’s disease is difficult to treat with
currently available therapies and often leads to pain, swelling,
infection and incontinence,” said Dr. Asit Parikh, Head of Takeda’s
Gastroenterology Therapeutic Area Unit. “Existing therapies are
limited and associated with complications and a high failure rate.
Cx601 may offer patients an alternative treatment option.”
“These data highlight that the efficacy and safety of a single
administration of Cx601 were maintained during one year of follow
up,” said Dr. Marie Paule Richard, Chief Medical Officer at
TiGenix. “It is important to also note that the definition of
combined remission used in the ADMIRE-CD study, which includes both
clinical and radiological assessment by MRI, is more stringent than
the criteria commonly used in previous large scale, randomized
clinical trials evaluating perianal fistulas in Crohn’s disease,
based only on clinical assessment.”
A global pivotal Phase 3 trial for U.S. registration with Cx601
for the treatment of complex perianal fistulas is expected to be
initiated by TiGenix in 2017. In the U.S., TiGenix intends to apply
for fast track designation from the U.S. Food and Drug
Administration (FDA), which would facilitate and expedite the
development and review process in the U.S.
Takeda’s Commitment to Gastroenterology
Takeda is a global leader in gastroenterology. With expertise
spanning more than 25 years, the company’s dedication to innovation
continues to evolve and have a lasting impact. ENTYVIO®
(vedolizumab) demonstrates Takeda’s global capabilities and
expansion into the specialty care market in gastroenterology and
biologics. Designed and developed specifically to target the
gastrointestinal (GI) tract, ENTYVIO was launched in 2014 for the
treatment of adults with moderate to severe ulcerative colitis and
Crohn’s disease. TAKECAB® (vonoprazan fumarate) is Takeda's
potassium-competitive acid blocker and was launched in Japan in
2015. Takeda also markets motility agent AMITIZA® (lubiprostone),
which originally launched in 2006 for the treatment of chronic
idiopathic constipation, and received subsequent approval to treat
irritable bowel syndrome with constipation and opioid-induced
constipation. Preceding these notable launches, Takeda pioneered
gastroenterological breakthroughs in proton pump inhibitors
beginning in the 1990’s with lansoprazole.Through specialized and
strategic in-house development, external partnerships, in-licensing
and acquisitions, Takeda currently has a number of promising early
stage GI assets in development, and remains committed to delivering
innovative, therapeutic options for patients with gastrointestinal
and liver diseases.
About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited is a global,
R&D-driven pharmaceutical company committed to bringing better
health and a brighter future to patients by translating science
into life-changing medicines. Takeda focuses its research efforts
on oncology, gastroenterology and central nervous system
therapeutic areas. It also has specific development programs in
specialty cardiovascular diseases as well as late-stage candidates
for vaccines. Takeda conducts R&D both internally and with
partners to stay at the leading edge of innovation. New innovative
products, especially in oncology and gastroenterology, as well as
its presence in emerging markets, fuel the growth of Takeda. More
than 30,000 Takeda employees are committed to improving quality of
life for patients, working with our partners in health care in more
than 70 countries. For more information, visit
http://www.takeda.com/news.
About TiGenix
TiGenix NV (Euronext Brussels and Nasdaq: TIG) is an advanced
biopharmaceutical company focused on developing and commercializing
novel therapeutics from its proprietary platforms of allogeneic, or
donor-derived, expanded stem cells. Our lead product candidate from
the adipose-derived stem cell technology platform is Cx601, which
is in registration with the EMA for the treatment of complex
perianal fistulas in Crohn’s disease patients. Our adipose-derived
stem cell product candidate Cx611 has completed a Phase I sepsis
challenge trial and a Phase I/II trial in rheumatoid arthritis.
Effective July 31, 2015, TiGenix acquired Coretherapix, whose lead
cellular product candidate, AlloCSC-01, is currently in a Phase II
clinical trial in acute myocardial infarction. In addition, the
second product candidate from the cardiac stem cell-based platform
acquired from Coretherapix, AlloCSC-02, is being developed in a
chronic indication. On July 4, 2016, TiGenix entered into a
licensing agreement with Takeda, a large pharmaceutical company
active in gastroenterology, under which Takeda acquired the
exclusive right to develop and commercialize Cx601 for complex
perianal fistulas outside the United States. TiGenix is
headquartered in Leuven (Belgium) and has operations in Madrid
(Spain).
About Cx601
Cx601 is a suspension of allogeneic expanded adipose-derived
stem cells (eASC) locally injected. Cx601 is an investigational
compound being developed in Crohn’s disease for the treatment of
complex perianal fistulas showing inadequate response to at least
one conventional or biologic therapy including antibiotics,
immunosuppressants, or anti-TNF agents. Crohn’s disease is a
chronic inflammatory disease of the intestine and, as a
complication of it, patients can suffer from complex perianal
fistulas, for which there is currently no effective treatment. In
2009, the European Commission granted Cx601 orphan designation for
the treatment of anal fistulas, recognizing the debilitating nature
of the disease and the lack of treatment options. Cx601 has met the
primary end-point in the Phase 3 ADMIRE-CD study, a randomized,
double-blind, controlled trial run in Europe and Israel and
designed to comply with the requirements laid down by the EMA.
‘Madrid Network’ issued a soft loan to help finance this Phase 3
study, which was funded by the Secretary of State for Research,
Development and Innovation (Ministry of Economy and
Competitiveness) within the framework of the INNTEGRA plan. In this
trial, patients were randomized to a single administration of Cx601
cells or placebo (control), both added to standard of care. The
study’s primary endpoint was combined remission, defined as
clinical assessment at week 24 of closure of all treated external
openings draining at baseline despite gentle finger compression,
and absence of collections >2cm confirmed by MRI. In the ITT
population (n=212), Cx601 achieved statistically significant
superiority (p=0.024) on the primary endpoint with 50% combined
remission at week 24 compared to 34% in the control arm. Efficacy
results were robust and consistent across all statistical
populations. Treatment emergent adverse events (non-serious and
serious) and discontinuations due to adverse events were comparable
between Cx601 and control arms. The 24-week results have been
published by The Lancet, one of the most highly regarded and well
known medical journals in the world. The Phase 3 study has
completed a follow-up analysis at 52 weeks confirming its sustained
efficacy and safety profile. Top line follow-up data showed that in
the ITT population Cx601 achieved statistical superiority (p=0.012)
with 54% combined remission at week 52 compared to 37% in the
control arm. Long-term results also showed that, of patients with
combined remission at week 24, a higher proportion of patients
treated with Cx601 had no relapse at week 52 (75.0% vs. 55.9%).
Based on the positive 24-weeks Phase 3 study results, TiGenix has
submitted a Marketing Authorization Application to the EMA in early
2016. TiGenix is preparing to develop Cx601 in the U.S. after
having reached an agreement with the FDA through a special protocol
assessment procedure (SPA) in 2015. On July 4, 2016, TiGenix
entered into a licensing agreement with Takeda, a pharmaceutical
company leader in gastroenterology, whereby Takeda acquired an
exclusive right to develop and commercialize Cx601 for complex
perianal fistulas in Crohn’s patients outside of the U.S.
-Ends-
____________
* defined as clinical assessment of
closure of all treated external openings draining at baseline,
despite gentle finger compression, and absence of collections
>2cm confirmed by MRI
References
1 Panés, J, García-Olmo, D, Van Assche, G, et al., Long-term
efficacy and safety of Cx601, allogeneic expanded adipose-derived
mesenchymal stem cells, for complex perianal fistulas in Crohn’s
Disease: 52-week results of a phase III randomized controlled
trial. ECCO 2017; Barcelona: Abstract OP009.
2 Clinicaltrials.gov. Adipose Derived Mesenchymal Stem Cells for
Induction of Remission in Perianal Fistulizing Crohn's Disease
(ADMIRE-CD).
https://clinicaltrials.gov/ct2/show/NCT01541579?term=cx601&rank=2.
Published February 2012. Accessed February 9, 2017.
3 Burisch, J, Jess, T, Martinato, M, et al., on behalf of ECCO –
EpiCom. The burden of inflammatory bowel disease in Europe. J
Crohn’s Colitis. 2013; 7: 322-337.
4 Swissmedic. About us – Collaboration – National collaboration
– Patients and Users. Available at
https://www.swissmedic.ch/ueber/01398/01400/03296/index.html?lang=en.
Accessed February 9, 2017.
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For TiGenix:Claudia D'AugustaChief
Financial Officerclaudia.daugusta@tigenix.com+34 91 804
9264orFor Takeda:Tsuyoshi TadaMedia in
Japantsuyoshi.tada@takeda.com+81 33 278 2417orLuke WillatsMedia
outside of JapanLuke.willats@takeda.com+41 44 555 1145