FDA Provides Guidance on Clinical Pathway to Marketing Application for Revascor in End-Stage Heart Failure Patients With an L...
August 27 2019 - 6:00AM
Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in cellular
medicines for inflammatory diseases, announced today positive
outcomes from its recent meeting with the United States Food and
Drug Administration (FDA) on the pathway for marketing
authorization of its allogeneic cell therapy product candidate
Revascor in end-stage heart failure patients implanted with a left
ventricular assist device (LVAD).
Key outcomes were:
- FDA reiterated that a reduction in major gastrointestinal
bleeding events and/or epistaxis, collectively termed major mucosal
bleeding events, is an important clinical outcome in patients
implanted with an LVAD.
- FDA confirmed that data from the recently completed 159-patient
placebo-controlled trial showing that Revascor reduced major
mucosal bleeding events can support product marketing
authorization through a Biologics License Application (BLA), with
confirmatory clinical data.
- FDA agreed on a confirmatory Phase 3 trial of Revascor in LVAD
patients, with a primary endpoint of reduction in major mucosal
bleeding events, and key secondary endpoints demonstrating
improvement in various parameters of cardiovascular function.
The confirmatory trial is planned to be conducted with the
International Center for Health Outcomes Innovation Research
(InCHOIR) at the Icahn School of Medicine at Mount Sinai in
New York, in line with an existing Memorandum of Understanding.
Mesoblast Chief Executive Dr Silviu Itescu said: “The FDA
guidance on the pathway to registration for our heart failure
product candidate in LVAD patients is a major step forward for our
cardiovascular program. We will work closely with the FDA and
InCHOIR to generate the confirmatory clinical data needed for full
marketing approval of Revascor in the prevention of this
life-threatening inflammatory complication of an LVAD implant in
end-stage heart failure patients.”
Revascor is being developed for these patients under existing
FDA Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug
Designations.
About Orphan Drug Designation The FDA’s Orphan
Drug Designation Program provides orphan status to drugs and
biologics which are defined as those intended for the safe and
effective treatment, diagnosis or prevention of rare diseases and
disorders that affect fewer than 200,000 people in the United
States. Orphan drug designation qualifies the sponsor for various
development incentives, including eligibility for seven years of
market exclusivity upon regulatory approval, exemption from FDA
application fees, tax credits for qualified clinical trials, and
other potential assistance in the drug development process.
About RMAT Designation The FDA’s RMAT
designation program under the 21st Century Cures Act aims to
expedite the development of regenerative medicine therapies
intended for the treatment of serious diseases and life-threatening
conditions. RMAT designation allows for multi-disciplinary,
comprehensive interactions with the FDA to support efficient
development of and potential accelerated approval pathway for cell
therapy candidates. The RMAT designation also offers eligibility
for priority review.
About End-Stage Heart Failure and LVADsIn the
United States, over 60,000 patients annually suffer from end-stage
heart failure, and despite optimal medical therapy these patients
have a one-year mortality exceeding 50%.1 The only options to
increase survival in these patients are the use of left ventricular
assist devices (LVADs) or heart transplants.
Due to the decline in organ donations and limited availability
of healthy donor hearts, the use of LVADs in end-stage heart
failure patients is gaining momentum, with approximately 5,500
LVADs implanted annually in the United States.2,3,4 However,
high rates of rehospitalization remain a major obstacle to greater
LVAD use, with up to 40% of patients being rehospitalized as a
result of major gastrointestinal bleeding.5,6
About Revascor in Heart FailureMesoblast’s
investigational cell therapy Revascor consists of 150 million
allogeneic mesenchymal precursor cells (MPCs) and is being
developed for injection into heart muscle of patients with
moderate-advanced or end-stage chronic heart failure.
Revascor for End-Stage Heart Failure Patients with
LVADsIn a 30-patient placebo-controlled pilot trial in
end-stage heart failure patients with LVADs, conducted by the
United States National Institutes of Health (NIH), a single
intra-myocardial dose of Revascor resulted in a 70% reduction in GI
bleeding and associated hospitalizations. The results of this pilot
trial were the basis of the RMAT designation granted in December
2017 by the FDA for use of Revascor in LVAD patients. In a
subsequent meeting in 2018, the FDA advised Mesoblast that the
defined endpoint of reduction in major GI bleeding and
rehospitalization is an appropriate clinically meaningful endpoint
and could be the basis of an approved indication for use of
Revascor given the life-threatening nature of the condition, and
the RMAT designation under which Revascor is being regulated. In
November 2018, NIH investigators presented results of a 159-patient
randomized placebo-controlled Phase 2 clinical trial at the
American Heart Association Scientific Sessions. In the Phase 2
trial, a single intra-myocardial injection of Revascor at the time
of LVAD implantation resulted in a 76% reduction in major GI
bleeding events and 65% reduction in related hospitalizations in
the overall patient population studied. In a post-hoc analysis in
patients with an ischemic cause of their heart failure, these
effects of Revascor were even greater, as well as an observed
significant increase in the ability to wean off device support,
suggesting strengthening of the native heart muscle.
Revascor in Patients with Moderate to Advanced Heart
FailureRevascor is being evaluated in a placebo-controlled
Phase 3 trial which has enrolled 566 patients with New York Heart
Association Class II/III moderate to advanced heart failure across
multiple sites in North America. The objectives of this Phase 3
events-driven trial are to evaluate the ability of Revascor to meet
the primary endpoint of reduction in recurrent heart
failure-related major adverse cardiac events (HF-MACE) in patients
with left ventricular dysfunction, as well as delay or prevent
disease progression to terminal cardiac events, defined as death,
left ventricular assist device (LVAD) implantation, or cardiac
transplant. The trial has accrued and validated approximately
90% of its required target of primary endpoint events. It is
expected that all the required primary endpoint events will be
accrued and validated by the end of CY 2019. In April 2017, the
Phase 3 trial was successful in a pre-specified futility analysis
of the primary efficacy endpoint in the first 270 patients.
About Mesoblast Mesoblast Limited (Nasdaq:
MESO; ASX: MSB) is a world leader in developing allogeneic
(off-the-shelf) cellular medicines. The Company has leveraged its
proprietary technology platform to establish a broad portfolio of
late-stage product candidates with three product candidates in
Phase 3 trials – acute graft versus host disease, chronic heart
failure and chronic low back pain due to degenerative disc disease.
Through a proprietary process, Mesoblast selects rare mesenchymal
lineage precursor and stem cells from the bone marrow of healthy
adults and creates master cell banks, which can be industrially
expanded to produce thousands of doses from each donor without the
need for tissue matching. Mesoblast has facilities in Melbourne,
New York, Singapore and Texas and is listed on the Australian
Securities Exchange (MSB) and on the Nasdaq (MESO).
www.mesoblast.com
References1 Gustafsson F, Rogers JG. Left
ventricular assist device therapy in advanced heart failure:
patient selection and outcomes. European Journal of Heart Failure
2017;19:595-602.2United Network for Organ Sharing.3Agency for
Healthcare Research and Quality – Healthcare Cost and Utilization
Project – Claims Analysis ICD- 37.6.4Data on file.5Chatterjee A,
Feldmann C, Hanke JS (2018) The momentum of HeartMate 3: a novel
active magnetically levitated centrifugal left ventricular assist
device (LVAD). J Thorac Dis 10 (Suppl 15): S1790-S1793.6Mehra, MR
Salerno C, Cleveland JC (2018) Health care resources use and cost
implications in the MOMENTUM 3 long-term outcome study: a
randomized controlled trial of a magnetically levitated cardiac
pump in advanced heart failure.
Forward-Looking Statements This announcement
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 timing,
progress and results of Mesoblast and its collaborators’ clinical
studies for LVAD patients; Mesoblast and its collaborators’ ability
to advance its product candidates into, enroll and successfully
complete, clinical studies for LVAD patients; and the timing or
likelihood of regulatory filings and approvals for use in LVAD
patients. 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
otherwise.
For further information, please contact:
Julie
Meldrum |
Schond
Greenway |
Corporate
Communications |
Investor Relations |
T: +61 3 9639 6036 |
T: +1 212 880 2060 |
E:
julie.meldrum@mesoblast.com |
E:
schond.greenway@mesoblast.com |
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