NEW YORK and MELBOURNE, Australia, Sept. 29, 2015 (GLOBE NEWSWIRE) -- Mesoblast Limited (ASX: MSB; USOTC:MBLTY) today announced that additional Phase 2 trial results of its lead product candidate for the treatment of chronic heart failure (CHF) were presented at the 19th Annual Scientific Meeting of the Heart Failure Society of America in National Harbor, MD, USA held from 26-29 September. The results showed that Mesoblast's mesenchymal precursor cell (MPC) therapy had the greatest cardioprotective effect in the subset of patients with more advanced heart failure.
A post-hoc analysis was performed in 30 patients from the Phase 2 trial who had been randomized to receive either placebo or a single administration of 150 million MPCs (MPC-150-IM). The results suggest that patients with advanced heart failure may be an optimal target population for treatment with Mesoblast's MPC therapy.
The objective of the analysis was to evaluate the efficacy of MPC-150-IM in patients with advanced heart failure, as defined by substantial baseline left ventricular (LV) contractile abnormality (LV end systolic volume, LVESV, greater than 100 ml). LVESV greater than 100 ml is more than three standard deviations above normal LVESV and is a predictor of poor long-term outcomes in patients with CHF. A further sensitivity analysis across every decile in baseline LVESV between 70 ml and 120 ml confirmed the findings seen in the stratification using a LVESV greater than 100 ml. Cardiac remodeling by echocardiography at baseline and 6 months, time-to-first heart failure-related major adverse cardiovascular event (HF-MACE) by Kaplan-Meier analysis and incidence of total (recurrent) HF-MACE over 36 months were assessed.
Key findings were:
-- control patients with baseline LVESV greater than 100 ml had the greatest deterioration (adverse remodeling) over 6 months in terms of worsening in both LVESV and left ventricular end diastolic volume (LVEDV), and loss of left ventricular ejection fraction (LVEF)
-- over a 6 month follow-up period, the 150 million MPC dose resulted in placebo-corrected significant reductions in LVESV of 57 ml (p equals 0.007) and LVEDV of 54 ml (p equals 0.004), and an increase in LVEF of 8.1 absolute percentage points (p equals 0.068) in patients with baseline LVESV greater than 100 ml
-- all of the HF-MACE seen over 36 months in the Phase 2 trial occurred in control patients with baseline LVESV greater than 100 ml; the annualized HF-MACE rate was 24% in this group, with an overall 71% HF-MACE rate over 36 months
-- in contrast, no HF-MACE were seen over the entire 36 months in 150 million MPC-treated patients with baseline LVESV greater than 100 ml (p equals 0.0007 when analyzed by Kaplan-Meier time-to-first-event analysis and p is less than 0.0001 by incidence analysis for total/recurrent HF-MACE, 0 versus 11 events).
Key conclusions are:
-- baseline LVESV greater than 100 ml identified a rapidly deteriorating sub-group of CHF patients with LV systolic dysfunction who experience a high rate of adverse outcomes
-- in these patients, a single administration of 150 million MPCs resulted in a significant cardioprotective effect and prevention of any HF-MACE over 36 months of follow up
-- patients with baseline LVESV greater than 100 ml may be an optimal target group for the potential cardioprotective benefits of MPC therapy.
An ongoing Phase 3 trial, using a time-to-first-event analysis of HF-MACE as the primary endpoint, is being conducted in 1,165 patients by Mesoblast's development and commercial partner, Teva Pharmaceutical Industries Ltd, across multiple sites in North America to investigate the use of MPC-150-IM in patients with advanced CHF.
The Phase 3 trial is enriched for patients with high baseline levels of NT-proBNP and a heart failure hospitalization within the last nine months, two inclusion criteria known to predict adverse outcomes in CHF. This enrichment is expected to result in the majority of enrolled patients having LV systolic dysfunction, baseline LVESV greater than 100 ml and high rates of HF-MACE.
Following recent discussions with the United States Food and Drug Administration, an interim analysis will be performed when 50% of the HF-MACE have occurred which will include a test for superiority allowing for the possibility of stopping of the trial early based on overwhelming efficacy.
The trial's Principal Investigator and lead author of the study, Dr Emerson C. Perin, Director of Research in Cardiovascular Medicine and Medical Director of the Stem Cell Center at the Texas Heart Institute, said: "Patients with advanced chronic heart failure and severe systolic contractile dysfunction represent a major medical need despite ongoing advances in cardiovascular medicine. The post-hoc analysis shows that this is an appropriate target population for Mesoblast's MPC therapy, and we hope to reproduce these findings in our ongoing Phase 3 trial."
Chronic Heart Failure
CHF is characterized by an enlarged heart and insufficient blood flow to the organs and extremities of the body. The condition, which affects 2% of the adult population of the United States, is progressive and can be caused by many factors that put an excess demand on the heart muscle such as high blood pressure, faulty valves, infections or congenital heart problems. CHF prevalence is expected to grow 46% by 2030, affecting more than 8 million Americans.
Mesoblast has been motoring along slowly but surely ....... and spending huge amounts of money along the way. Amazing what a good partnership deal can do.
In their CHF trial they use a SINGLE injection of their precursor cells. The question I have is why CYTX does not also try the single injection option instead of multiple injections which appear to create greater risk and stress for the patient? Also it alleviates the problem of having a skilled surgeon undertaking a very long tedious and risky intervention which is also NOT cost effective in terms of the surgeons time.
I appreciate that the previous CYTX trials for CHF have had multiple injections around the infarct and that may create a problem with change of protocol with the FDA. However given the risk parameters and physician time required for the procedure it would appear to me to be a no brainer that they should change the protocol. I would hope they are discussing this with the FDA and hopefully some potential partners.
CHF is a much higher value/need indication than breast reconstruction. It would be a shame for it not to proceed because we are making it a time consuming procedure (unnecessarily?) as was the case with RESTORE-2. We already have an invasive procedure (lipo) vis a vis the ease of the allogeneic option. It would be financially suicidal to have a trial as complex as that specified in the existing protocol. I think that our autologous product could be better and the marginal cost of producing it with Celution is very little.
Perin is the lead in the Mesoblast trial and is familiar with Celution. Surely this has been discussed?
Which leads me to the other questions, (1) where is the ADVANCE efficacy data, (2) where is the ATHENA data (3) how do they compare to the Mesoblast data?
$57M market cap ????????????????????????????????? WTF
Hedge you are correct that it is not feasible for CYTX to undertake any activity in CHF. Lets not forget however that this indication is being funded by TEVA for Mesoblast. Although unlikely to happen in CYTX case it shows that there is capital (non-dilutive) available if you are prepared to partner.
Lets hope that the data is available in November and is positive. Eventually this indication will proceed. The purpose of my original post was to point out the importance of choosing the optimal trial procedure (single injection?).
Lets hope that the Scleroderma and OA trials are successful. This will determine whether we someday see Celution trialed and treating CHF.
The Athena data has been submitted to be presented at an AHA meeting in November. From last CC:
As I mentioned the long term follow up data from SCLERADEC-II is [is in press] [ph] and we
[indiscernible] planned release but as mentioned previously the data looks good. The Athena
interim six months data has been submitted to the American Heart Association meeting and
we’re waiting for feedback on the acceptance of that abstract in theory that would be presented
The Athena 12 month data, we’ve just obtained and that’s under evaluation and will keep you
posted as to how we’re going to put that data out there and then we have some other burn
publications that are pending as well. So a number of things coming forth for the publication and
data release side.
The results are going to have to be spectacular to attract a partner and it will be difficult get statistical significance given the limited number of patients treated.
Abstracts will be available online Friday, November 6, 2015 at 4:00 PM ET. Abstracts and presentations are embargoed until the day and time of presentation or time of AHA news event and no information may be released before then. Failure to honor embargo policies will result in abstract being withdrawn or barred from presentation.
There are some sessions on November 10 that would fit the bill..
Even if this app is not relevant at present... I am sure it will become relevant at some point in time when the technology is a few steps further.
Board moderator and Site-owner. I still regret the day I started analysing the prospects of MacroPore (now Cytori) back in 2004- a left-over from the tech-bubble at that time from the century change in my portfolio- and became addicted to Cytori´s fat cell technology.
More Interesting News on Mesoblast CHF Trial
01 Oct 2015 10:20 #5267
CHF another failed indication just like every other indication that management promised was a focus of the company and would be generating revenue. What happened to breast reconstruction, Japan, Lorem,Okyanos,Barda or any of the other indications. Europe approvals alone was supposed to generate enough revenues to get to a break even. Go back and listen to calls and promises made 5 years ago still waiting. Come to think of it still waiting for answers to questions posted on this site 2 years ago by Fas that management promised to answer. Transparency, better shareholder communication, 10 times your wildest dreams,partnerships on the way.. All pie in the sky bullshit from a company going nowhere fast. How's that deesdale facility doing guess the cookies must be really stale by now. Just disgusting
Even if this app is not relevant at present... I am sure it will become relevant at some point in time when the technology is a few steps further. ***
The procedure may be used extensively one day Fas, its just Cytori's patents will no longer matter by then. They will have to start over with trial design before they dump more money into it. Okyanos is lucky they were able to treat other indications. Lim made the same poor bet as the rest of us...LOL ! Rothco....you forgot all the cardiac patients in India that were going to be treated....another easily spotted folly imho and one I never believed. The key to surviving a CYTX investment was not going along with every utterance as fact and limiting investment as one should in every speculative equity. This investment may yet pay but cardiology is a pipe dream for many many years and will not be the indication that saves the company.
Big change from Down Under...
PHASE 3 HEART FAILURE TRIAL SIZE TO BE SUBSTANTIALLY REDUCED
FOLLOWING FDA DISCUSSIONS
New York, USA; and Melbourne, Australia; 11 January 2016: Mesoblast Limited (ASX:MSB;
Nasdaq:MESO) today announced that the size of the ongoing Phase 3 trial in chronic heart failure
(CHF) of its proprietary cell-based medicine MPC-150-IM is planned to be substantially reduced.
This follows communications last month between Mesoblast’s development and commercial partner,
Teva Pharmaceutical Industries Ltd., and the United States Food and Drug Administration (FDA).
Mesoblast Chief Executive Silviu Itescu said: “The reduction in the size of the Phase 3 trial may
significantly shorten the time to trial completion."
The ongoing Phase 3 program is planned to be optimized as follows:
• The FDA has agreed to a reduction in the current Phase 3 trial size from 1,165 to
approximately 600 patients due to a proposed change in the primary endpoint
• The revised primary endpoint will be a comparison of recurrent heart failure-related major
adverse cardiovascular events (HF-MACE) between patients treated with MPC-150-IM and
• The proposed use of recurrent HF-MACE as a primary endpoint in the Phase 3 trial is based
on the fact that a single injection of MPC-150-IM successfully prevented recurrent HF-
MACE over three years in the Phase 2 trial
• A second confirmatory study will be conducted in parallel in an identical patient population
of approximately 600 subjects using the same primary endpoint.
In the completed Phase 2 trial, patients treated with MPC-150-IM had no HF-MACE over 36 months
of follow-up, compared with 11 HF-MACE events in the control group (p<0.001, log rank test). In
patients with advanced heart failure as defined by baseline Left Ventricular Systolic Volume
>100ml, who closely resemble the patients being recruited in the Phase 3 trial, 71% of controls
had at least one HF-MACE event vs 0 of those who received a single injection of MPC-150-IM
“Patients with advanced heart failure continue to represent among the largest unmet medical
needs, where existing therapies are inadequate and the economic burden is the greatest. The
current Phase 3 trial targets this patient population, continues to recruit well across North America,
and is now expanding to Europe,” Dr Itescu added.
Chronic Heart Failure
CHF is characterized by an enlarged heart and insufficient blood flow to the organs and extremities
of the body. The condition is progressive and can be caused by many factors that put an excess
demand on the heart muscle such as high blood pressure, faulty valves, infections or congenital
heart problems. The American Heart Association reports 5.7 million adults in the United States
with diagnosed CHF, or about 2% of the adult population, with 870,000 new cases diagnosed each
year. New York Heart Association Class II / III CHF patients with low ejection fraction continue to
be at high risk of repeated hospitalizations and mortality, despite standard of care pharmacological
treatments. CHF prevalence is expected to increase by 46% by 2030, affecting more than 8 million
Americans. The estimated annualized cost for CHF is approximately $32 billion, and is projected to
grow to $77 billion by 2030.
The following user(s) said Thank You: myownhedgefund
yep Hedge, and the FDA is on board. Going to save them mucho denaro and the endpoint has been greatly simplified. Trying to figure out what it means towards getting approval and if approval will be worth the same as it would have been with the original primary endpoints.
Wall Street Titan wrote: yep Hedge, and the FDA is on board. Going to save them mucho denaro and the endpoint has been greatly simplified. Trying to figure out what it means towards getting approval and if approval will be worth the same as it would have been with the original primary endpoints.
Great news for this market and also shows the FDA in amenable .