Remestemcel-L Improves Survival of Children With Biomarkers for Highest Mortality in Steroid Refractory Acute GVHD
October 18 2021 - 8:00AM
Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in
allogeneic cellular medicines for inflammatory diseases, today
announced that results published in the latest issue of the
peer-reviewed journal Bone Marrow Transplantation1 showed that
children with steroid-refractory acute graft versus host disease
(SR-aGVHD) and biomarkers predictive for highest mortality had 64%
survival when treated with remestemcel-L compared with only 10%
survival when treated with other available therapies, including
ruxolitinib or other biologics.
The study’s senior author and expert in the predictive
biomarkers, Dr. James Ferrara, Ward-Coleman Chair in Cancer
Medicine, Professor and Director Hematologic Malignancies
Translational Research Center at The Icahn School of Medicine at
Mount Sinai Hospital, said: “The findings support and extend recent
studies that children with severe, SR acute GVHD benefit from
remestemcel-L therapy.”
These data provide further support for the proposed
anti-inflammatory mechanism of action of remestemcel-L and its
immunomodulatory activity in patients with SR-aGVHD, resulting in
improved survival outcomes. At its upcoming scheduled meeting with
FDA’s Office of Tissue and Advanced Therapies (OTAT), Mesoblast
will address the appropriateness of potency assays related to
remestemcel-L’s proposed anti-inflammatory mechanism of action as
well as the outstanding chemistry, manufacturing and controls (CMC)
items which could support a resubmission of the current Biologics
License Application (BLA) for remestemcel-L in the treatment of
SR-aGVHD in children.
Summary of the study outcomes
The study compared outcomes in 25 children from Mesoblast’s
Phase 3 trial of remestemcel-L in SR-aGVHD with 27 closely matched
children from the Mount Sinai Acute GVHD International Consortium
(MAGIC)2 who participated in a prospective natural history study
and were matched for the Phase 3 trial entry criteria. The
objective of the study was to evaluate whether outcomes differed
according to treatment with remestemcel-L vs other therapies in
children at highest risk of death, namely those with baseline MAGIC
Algorithm Probability (MAP) biomarker levels ≥0.291, a level
predictive of very high mortality and poor responses to therapy in
SR-aGVHD. MAP combines the serum concentrations of two biomarkers,
Reg3α and ST2, into a single value that predicts long-term outcomes
and significant GI tract damage.
MAP levels ≥0.291 were present in 48% of remestemcel-L treated
children (12/25) and 37% of the MAGIC cohort (10/27). Treatment
with remestemcel-L resulted in 67% Day 28 Overall Response and 64%
Day 180 overall survival compared with 10% Day 28 Overall Response
and 10% Day 180 survival in the MAGIC cohort (both p=0.01) when
treated with various biologics, including ruxolitinib. These
results extend previous observations showing that children who
achieved clinically meaningful responses and survival after
treatment with remestemcel-L had significant reductions in the ST2
biomarker of inflammation, consistent with healing of the GI
tract.3
About Steroid-Refractory Acute Graft Versus Host Disease
(SR-aGVHD) GVHD is a severe inflammation in the
bloodstream caused by complications of bone marrow transplants. The
disease occurs in up to 50% of the 30,000 patients who receive an
allogeneic bone marrow transplant each year, primarily during
treatment for blood cancers. In patients with the most severe form
of GVHD, mortality can be as high as 90%. There are no therapies
approved for treating SR-aGVHD in children under the age of 12.
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 has completed Phase 3 trials of rexlemestrocel-L for
advanced chronic heart failure and chronic low back pain.
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. 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
Footnotes
- Kasikis S., et al. Mesenchymal stromal cell therapy induces
high responses and survival in children with steroid refractory
GVHD and poor risk. Bone Marrow Transplantation 2021;
https://doi.org/10.1038/s41409-021-01442-3
- Mount Sinai Acute GVHD International Consortium (MAGIC) - a
group of ten BMT centers throughout the US and Europe whose purpose
is to conduct ground-breaking clinical trials in GVHD, including
developing informative biorepositories that assist in developing
treatments that can guide GVHD therapy
- Presented at the annual meeting of the American Society of
Hematology (ASH) 2020
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