Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in
allogeneic cellular medicines for inflammatory diseases, today
announced positive results from an interim analysis of the first
patient cohort in the randomized, controlled study of remestemcel-L
by direct endoscopic delivery to areas of inflammation in patients
with medically refractory ulcerative colitis or Crohn’s colitis. A
single local delivery of remestemcel-L by colonoscopy resulted in
rapid mucosal healing and disease remission in these refractory
patients at high risk of progression to surgery.
The results of the first cohort of patients were presented at
the 17th Congress of European Crohn’s and Colitis Organisation
(ECCO), February 16-19, by the trial’s lead investigator Dr. Amy L.
Lightner, Associate Professor of Surgery in the Department of Colon
and Rectal Surgery at Cleveland Clinic and were published in the
Journal of Crohn's and Colitis.1,2
“Mesenchymal stromal cells (remestemcel-L) offer a safe
therapeutic for the treatment of medically refractory Ulcerative
Colitis and Crohn’s colitis,” said Dr. Lightner. “Early data
suggests improved clinical and endoscopic scores as early as two
weeks following remestemcel-L delivery.”
The study at Cleveland Clinic will randomize up to 48 patients
with medically refractory ulcerative colitis or Crohn’s colitis in
a 2:1 fashion to receive a single intervention with remestemcel-L
at a dose of 150-300 million cells or placebo delivered via direct
injection using a 23 G sclerotherapy needle at the time of
colonoscopy. Medically refractory ulcerative colitis and Crohn’s
colitis patients are defined as having active disease for at least
6 months and having lost response to at least one monoclonal
antibody (anti-TNF or anti-integrin). Medically refractory Crohn’s
colitis patients exclude small bowel involvement and colorectal
strictures. Outcomes are evaluated by validated endoscopic and
clinical scoring systems at 2 weeks, 6 weeks, and 3 months post
intervention.3,4
Key results of the interim analysis performed in the first 12
enrolled patients were as follows:
- Colonoscopic delivery of remestemcel-L
was not associated with any treatment-related adverse events
- All ulcerative colitis patients treated
with remestemcel-L had improved clinical and endoscopy scores
within two weeks, as defined by the Mayo clinical score and Mayo
endoscopic severity (MES) score, and all achieved clinical and
endoscopic remission by six weeks
- All ulcerative colitis patients were
extremely satisfied or satisfied with remestemcel-L treatment at
three months, based on the inflammatory bowel disease patient
reported treatment impact (IBD-PRTI), and response was described as
excellent or good in all patients
- All Crohn’s colitis patients treated
with remestemcel-L showed treatment remissions or responses by
three months, as measured by the Simple Endoscopy Score for Crohn’s
Disease (SES-CD) (mean score 17 at baseline decreased to 5 at three
months)
- Remestemcel-L treatment resulted in
reduction of fecal calprotectin, a validated biomarker of disease
activity,5 from mean of 231 at baseline to 67 at three months,
indicative of remission
- In controls with ulcerative colitis and
Crohn’s colitis over three months, endoscopy scores increased,
fecal calprotectin levels increased from a mean of 330 to 505, and
clinical responses were described as poor or unchanged
Mesoblast Chief Medical Officer, Dr. Eric Rose said, “We are
delighted to be involved with Dr. Lightner and her team at
Cleveland Clinic in this latest cutting-edge study. This randomized
controlled trial is the first to evaluate local delivery of
remestemcel-L directly into the inflamed colon, using objective
endoscopic measures of mucosal healing, in patients with colitis
who are at high risk of surgical resection of their colon.”
About Inflammatory Bowel DiseaseAccording to
recent estimates, more than three million people (1.3%) in the US
alone have inflammatory bowel disease, with more than 33,000 new
cases of Crohn’s disease and 38,000 new cases of ulcerative colitis
diagnosed every year.6-8 Despite recent advances, approximately 30%
of patients are primarily unresponsive to anti-TNFα agents and even
among responders, up to 10% will lose their response to the drug
every year. Up to 80% of patients with medically-refractory Crohn’s
disease and 20% of patients with medically-refractory ulcerative
colitis eventually require surgical treatment of their disease,9,10
which can have a devastating impact on quality of life.
About Objective Measures of Disease Activity in Patients
with Inflammatory Bowel Disease
Objective measurement of disease activity can be achieved by
endoscopy, histopathology, imaging, and biomarkers.3 Fecal
calprotectin is a very sensitive biomarker for inflammation in the
gastrointestinal tract, with the presence of calprotectin a result
of neutrophil migration into the gastrointestinal tissue due to an
inflammatory process.5 It is used for the diagnosis of inflammatory
bowel disease, including ulcerative colitis and Crohn’s disease,
for monitoring disease activity and response to treatment, for
prediction of disease relapse and post-operative recurrence in
inflammatory bowel disease, and for predicting those patients at
highest risk of progressing to bowel resection.5
Regulatory guidance recommends that registration trials of
potential therapies for ulcerative colitis use primary endpoints
incorporating both endoscopy and patient-reported outcomes (PROs).3
Clinical trials for ulcerative colitis most commonly use the Mayo
endoscopic subscore (MES) and the composite Mayo Clinic Score. FDA
has consistently recommended the inclusion of endoscopic evaluation
of mucosal healing in Crohn’s disease as a co-primary endpoint to
ensure that a clinical improvement is accompanied by a benefit in
the underlying disease process. Simple Endoscopic Score for Crohn’s
Disease (SES-CD) is a reliable and responsive instrument,4 but
correlates poorly with symptoms. The current regulatory
recommendation for trial eligibility is an SES-CD score > 6 to
define baseline endoscopic disease severity, with endoscopic
remission defined by an SES-CD score of 0 to 2, and endoscopic
response defined by a 50% reduction in the SES-CD score from
baseline.
About Mesoblast Mesoblast is a world leader in
developing allogeneic (off-the-shelf) cellular medicines for the
treatment of severe and life-threatening inflammatory conditions.
The Company has leveraged its proprietary mesenchymal lineage cell
therapy technology platform to establish a broad portfolio of
late-stage product candidates which respond to severe inflammation
by releasing anti-inflammatory factors that counter and modulate
multiple effector arms of the immune system, resulting in
significant reduction of the damaging inflammatory process.
Mesoblast has a strong and extensive global intellectual
property portfolio with protection extending through to at least
2041 in all major markets. The Company’s proprietary manufacturing
processes yield industrial-scale, cryopreserved, off-the-shelf,
cellular medicines. These cell therapies, with defined
pharmaceutical release criteria, are planned to be readily
available to patients worldwide.
Mesoblast is developing product candidates for distinct
indications based on its remestemcel-L and rexlemestrocel-L stromal
cell technology platforms. Remestemcel-L is being developed for
inflammatory diseases in children and adults including steroid
refractory acute graft versus host disease and moderate to severe
acute respiratory distress syndrome. Rexlemestrocel-L is in
development for advanced chronic heart failure and chronic low back
pain. Two products have been commercialized in Japan and Europe by
Mesoblast’s licensees, and the Company has established commercial
partnerships in Europe and China for certain Phase 3 assets.
Mesoblast has locations in Australia, the United States and
Singapore and is listed on the Australian Securities Exchange (MSB)
and on the Nasdaq (MESO). For more information, please see
www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter:
@Mesoblast
References / Footnotes
- Lightner A., et al. A Phase IB/IIA study of remestemcel-L, an
allogeneic bone marrow derived mesenchymal stem cell product, for
the treatment of medically refractory Crohn’s colitis: A
preliminary analysis. Journal of Crohn's and Colitis, Volume 16,
Issue Supplement_1, January 2022, Pages i412–i413,
https://doi.org/10.1093/ecco-jcc/jjab232.555
- Lightner A., et al. A Phase IB/IIA study of remestemcel-L, an
allogeneic bone marrow derived mesenchymal stem cell product, for
the treatment of medically refractory ulcerative colitis: An
interim analysis. Journal of Crohn's and Colitis, Volume 16, Issue
Supplement_1, January 2022, Pages i398–i399,
https://doi.org/10.1093/ecco-jcc/jjab232.534
- Abreu MT and Sandborn WJ. Defining Endpoints and Biomarkers in
Inflammatory Bowel Disease: Moving the Needle Through Clinical
Trial Design. Gastroenterology 2020;159:2013–2018
- Daperno M, et al. Development and validation of a new,
simplified endoscopic activity score for Crohn’s disease: the
SES-CD. Gastrointest Endosc 2004;60:505–512.
- Pathirana GW, et al. Faecal Calprotectin. Clin Biochem Rev.
2018 Aug; 39(3): 77–90.
- CDC Facts and Figures 2015
- Globaldata Pharmapoint 2018
- Dahlhamer JM, MMWR Morb Mortal Wkly Rep.
2016;65(42):1166–1169.
- Crohn’s and Colitis Foundation
- Lightner AL. Surgery for Inflammatory Bowel Disease in the ERA
of Biologics. J Gastroinest Surg. 2020 Vol 24: 1430-1435
Forward-Looking Statements
This press release includes forward-looking statements that
relate to future events or our future financial performance and
involve known and unknown risks, uncertainties and other factors
that may cause our actual results, levels of activity, performance
or achievements to differ materially from any future results,
levels of activity, performance or achievements expressed or
implied by these forward-looking statements. We make such
forward-looking statements pursuant to the safe harbor provisions
of the Private Securities Litigation Reform Act of 1995 and other
federal securities laws. Forward-looking statements should not be
read as a guarantee of future performance or results, and actual
results may differ from the results anticipated in these
forward-looking statements, and the differences may be material and
adverse. Forward-looking statements include, but are not limited
to, statements about: the initiation, timing, progress and results
of Mesoblast’s preclinical and clinical studies, and Mesoblast’s
research and development programs; Mesoblast’s ability to advance
product candidates into, enroll and successfully complete, clinical
studies, including multi-national clinical trials; Mesoblast’s
ability to advance its manufacturing capabilities; the timing or
likelihood of regulatory filings and approvals (including BLA
resubmission), manufacturing activities and product marketing
activities, if any; the commercialization of Mesoblast’s product
candidates, if approved; regulatory or public perceptions and
market acceptance surrounding the use of stem-cell based therapies;
the potential for Mesoblast’s product candidates, if any are
approved, to be withdrawn from the market due to patient adverse
events or deaths; the potential benefits of strategic collaboration
agreements and Mesoblast’s ability to enter into and maintain
established strategic collaborations; Mesoblast’s ability to
establish and maintain intellectual property on its product
candidates and Mesoblast’s ability to successfully defend these in
cases of alleged infringement; the scope of protection Mesoblast is
able to establish and maintain for intellectual property rights
covering its product candidates and technology; estimates of
Mesoblast’s expenses, future revenues, capital requirements and its
needs for additional financing; Mesoblast’s financial performance;
developments relating to Mesoblast’s competitors and industry; and
the pricing and reimbursement of Mesoblast’s product candidates, if
approved. You should read this press release together with our risk
factors, in our most recently filed reports with the SEC or on our
website. Uncertainties and risks that may cause Mesoblast’s actual
results, performance or achievements to be materially different
from those which may be expressed or implied by such statements,
and accordingly, you should not place undue reliance on these
forward-looking statements. We do not undertake any obligations to
publicly update or revise any forward-looking statements, whether
as a result of new information, future developments or
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Release authorized by the Chief Executive.
For more information, please contact:
Corporate Communications
/ Investors |
Media |
Paul Hughes |
Sumit Media |
T: +61 3 9639 6036 |
Grant Titmus |
E: investors@mesoblast.com |
T: +61 419 388 161 |
|
E: grant@sumitmedia.com.au |
|
|
|
Rubenstein |
|
Nadine Woloshin |
|
T: +1 917-699-9456 |
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E: nwoloshin@rubenstein.com |
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