Ninety Day Survival Outcomes in COVID-19 ARDS Trial of Remestemcel-L Presented at ISCT Meeting on Advances in Cell & Gene The...
July 18 2021 - 8:58PM
Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in
allogeneic cellular medicines for inflammatory diseases, presented
90-day survival outcomes from the 222-patient randomized controlled
trial of remestemcel-L in ventilator-dependent COVID-19 patients
with moderate/severe acute respiratory distress syndrome (ARDS) at
an invited presentation on July 17 to the International Society for
Cell & Gene Therapy (ISCT) Scientific Signatures Series on Cell
and Gene Therapies in Lung Diseases and Critical Illnesses. The
results showed that two doses of remestemcel-L at days 3-5
conferred durable survival benefit through at least 90 days in the
pre-specified subgroup of patients under age 65.
Key presentation findings were:
- Remestemcel-L significantly reduced mortality by 48% at 90 days
compared to controls in a pre-specified analysis of 123 treated
patients under 65 years old, 26% vs 44%, Hazard Ratio (HR) 0.52,
95% CI (0.277, 0.964), p=0.038.1,2 This compares favourably with
the 46% mortality reduction reported at 60 days (p=0.048)1,2 and
indicates a durable treatment benefit in this patient
population.
- Remestemcel-L was even more effective when evaluated in an
exploratory analysis in patients on dexamethasone as part of their
standard of care, with 90-day mortality being reduced by 77%
compared to controls under 65 who received dexamethasone, 14% vs
48%, HR 0.23, 95% CI (0.080, 0.681), p=0.00371,2
- These survival benefits were accompanied by significant
improvements relative to controls in pre-specified secondary
endpoints of ventilator-free days, respiratory function as assessed
by ARDS severity, and overall clinical improvement on a 7-point
ordinal scale.
- Despite a treatment-related improvement in respiratory function
at day 7, there was no mortality reduction in the 97 treated
patients over age 65, suggesting the need for more prolonged or
higher dosing of anti-inflammatory therapy in these patients who
may have a more exuberant inflammatory response associated with
defective immune-mediated viral clearance mechanisms.
Recently published guidance to industry by the
U.S. Food and Drug Administration (FDA)3 has recommended
demonstration of mortality benefit for at least 60 days in
critically ill patients. Mesoblast will be meeting shortly with the
FDA to discuss the durable mortality reduction seen in patients
under 65 years old who received remestemcel-L in this randomized
controlled trial, and the regulatory pathway for remestemcel-L in
this patient population.
Mesoblast entered into a license and collaboration
agreement with Novartis for the development, manufacture, and
commercialization of remestemcel-L, with an initial focus on the
treatment of acute respiratory distress syndrome (ARDS), including
that associated with COVID-19. The agreement remains subject to
certain closing conditions, including time to analyze the results
from this COVID-19 ARDS trial.
About the Trial of Remestemcel-L in Acute
Respiratory Distress Syndrome (ARDS) due to COVID-19 The
trial enrolled 222 mechanically ventilated COVID-19 patients with
moderate/severe ARDS across the US, of whom 217 were
randomized 1:1 and received either standard of care alone
or standard of care plus 2 intravenous infusions of
remestemcel-L at a dose of 2 million cells/kg 3-5 days apart.
This was the same remestemcel-L dosing regimen used in the earlier
compassionate use program where 11 of 12 patients were younger
than 65 and 75% successfully came off ventilatory support.
The trial was halted in December 2020 after the
Data Safety Monitoring Board (DSMB) performed a third interim
analysis on the trial’s first 180 patients, noting that the trial
was not likely to meet the 30-day mortality reduction endpoint at
the planned 300 patient enrolment. The trial was powered to achieve
a primary endpoint of 43% reduction in mortality at 30 days for
treatment with remestemcel-L on top of maximal care. The DSMB
recommended that the trial complete with the enrolled 222 patients,
and that all be followed-up as planned.
At follow-up through day 60, remestemcel-L showed
a positive but non-significant trend in overall mortality reduction
across the entire population of treated patients (n=217). In the
pre-specified population of patients under age 65 (n=123),
remestemcel-L reduced mortality through day 60 by 46%, but not in
patients 65 or older (n=94). In an exploratory analysis through day
60, remestemcel-L reduced mortality by 75% and increased days alive
off mechanical ventilation in patients under age 65 when combined
with dexamethasone, in comparison with controls on
dexamethasone.
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 2040 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
- All p-values are descriptive and not adjusted for
multiplicity
- Hazard Ratios calculated using Cox regression proportional
hazards model without adjustment; p-value from log rank test
- COVID-19: Developing Drugs and Biological Products for
Treatment or Prevention - Guidance for Industry. U.S. Department of
Health and Human Services; Food and Drug Administration; Center for
Drug Evaluation and Research (CDER); Center for Biologics
Evaluation and Research (CBER). February 2021
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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 |
|
|
|
Kristen
Bothwell |
|
T: +1 917
613 5434 |
|
E:
kbothwell@rubenstein.com |
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