Ann: Mesoblast Phase 3 Chronic Heart Failure Results, page-11

Melbourne, Australia; December 15, and New York, USA; December 14, 2020: Mesoblast
Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory
diseases, today announced top-line results from the landmark DREAM-HF Phase 3 randomized
controlled trial of its allogeneic cell therapy rexlemestrocel-L (REVASCOR®) in 537 patients with
advanced chronic heart failure1.
Over a mean 30 months of follow-up, patients with advanced chronic heart failure who received a
single endomyocardial treatment with rexlemestrocel-L on top of maximal therapies had 60%
reduction in incidence of heart attacks or strokes and 60% reduction in death from cardiac causes
when treated at an earlier stage in the progressive disease process. Despite significant reduction in
the pre-specified endpoint of cardiac death, there was no reduction in recurrent non-fatal
decompensated heart failure events, which was the trial’s primary endpoint. This suggests that
rexlemestrocel-L reduces mortality by mechanisms that are distinct from those of existing drugs that
reduce hospitalization rates but do not significantly impact cardiac mortality.
“There is an urgent need for new therapies that can reduce the high death rates in heart failure
patients by different modes of action from existing drugs which reduce hospitalization rates but have
not significantly reduced mortality rates,” said Mesoblast Chief Executive Dr Silviu Itescu. “The
reduction in mortality seen with rexlemestrocel-L in advanced chronic heart failure underlines the
power of this technology and the commitment of Mesoblast to address diseases in patients with high
unmet need which are refractory to existing therapies.”
Key highlights were that a single injection of rexlemestrocel-L, on top of maximal therapy, resulted in
the following pre-specified outcomes over a 30-month mean follow-up period:
• Significant reduction in the incidence of non-fatal ischemic major adverse cardiac events
(MACE) due to a heart attack (myocardial infarction, MI) or stroke (cerebrovascular accident,
CVA) by 60% relative to controls in the total population of 537 patients (p=0.002); reduction
in MACE was seen consistently across both New York Heart Association (NYHA) class II or III
populations and irrespective of whether the underlying cause of heart failure was ischemic or
non-ischemic
• Significant reduction in death from all cardiac causes (CV death) in the 206 heart failure
patients with NYHA class II disease by 60% relative to controls (p=0.037), which was evident
in both ischemic and non-ischemic subgroups
• Prevention of NYHA class II patients progressing to CV death rates of NYHA class III patients
(p=0.004); in contrast, NYHA class II patients on maximal therapy in the control group
progressed to CV death rates of NYHA class III patients after a mean period of 20 months of
disease stability
• Significant reduction in the composite of the pre-specified CV death or ischemic MACE
outcomes in heart failure patients with NYHA class II disease by 55% relative to controls
(p=0.009)
“The trial results show that rexlemestrocel-L significantly reduces cardiovascular mortality when used
early in heart failure patients at risk of disease progression, and provides durable protection from
heart attacks or strokes in these vulnerable patients,” said the trial’s co-principal investigator Dr
Emerson Perin, Director of the Center for Clinical Research, Medical Director of Texas Heart Institute,
and Clinical Professor, Baylor College of Medicine. “New therapies have not materially reduced the
high death rates from cardiovascular disease which is why these data have the potential to change the
treatment paradigm for patients with advanced chronic heart failure.”
Mesoblast Chief Medical Officer Dr Fred Grossman said: “We expect the mortality benefit observed in
this seminal Phase 3 trial will support a potential path for approval of rexlemestrocel-L in patients with
advanced chronic heart failure. We are planning to meet and discuss potential pathways to approval
based on mortality reduction with the United States Food and Drug Administration.”
Conference Call
There will be a webcast today beginning at 9.00am AEDT (Tuesday, December 15); 5.00pm EST
(Monday, December 14, 2020). It can be accessed via https://webcast.boardroom.media/mesoblastlimited/20201214/NaN5fd6e483de11ae0019f60917
The archived webcast will be available on the Investor page of the Company’s website:
www.mesoblast.com
About the DREAM HF Phase 3 Trial
Clinical outcomes were evaluated in 537 advanced heart failure patients (206 with New York Heart
Association, NYHA, class II disease and 331 with NYHA class III disease) randomized 1:1 to either a
sham procedure or a transendocardial injection by catheter of rexlemestrocel-L (150 million cells).
Inclusion criteria enriched the trial for patients with advanced disease by requiring a prior heart failure
hospitalization over the past nine months or a N-terminal pro–B-type natriuretic peptide (NT-proBNP)
level of at least 1000 pg/ml. All patients were continued on maximal oral agents for heart failure, and
were followed for at least twelve months post-procedure.
Baseline characteristics showed that both patient groups with NYHA class II or NYHA class III clinical
grades had advanced disease, but those with NYHA class III disease had significantly greater severity
(mean NT-proBNP 2568 pg/ml for NYHA class III vs 1842 pg/ml for NYHA class II, p=0.001).
Recurrent non-fatal heart failure MACE, incidence of ischemic MACE due to a heart attack or stroke,
and death from cardiovascular causes (CV death), were evaluated over a mean follow-up period of 30