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TOPIC: Abstract from NBS board

Abstract from NBS board 17 Nov 2014 16:17 #2699

  • myownhedgefund
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AbstractBackground: ST segment Elevation Myocardial Infarction (STEMI) affects 160,000 annually in the US. Guidelines direct immediate revascularization and adjunctive medical therapies. Yet STEMI victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization and death. In pre-clinical studies, human CD34+ stem cells are angiogenic within ischemic myocardium, improving perfusion and function. A precedent Phase 1 study demonstrated feasibility, safety and bioactivity of intracoronary infusion of autologous CD34+ cells in patients with LV dysfunction (LVD) post-MI and identified a threshold dose of 10M cells associated with improved infarct region perfusion.
Methods: PreSERVE-AMI is a Phase 2, randomized, double-blind, placebo-controlled trial performed at 60 sites in the US. Those with LVD (EF≤48% by CMR) ≥4 days post-STEMI underwent mini bone marrow harvest and were randomized 1:1 to (A) autologous CD34+ cells (minimum dose of 10M±20% cells in autologous serum) or (B) autologous serum. (A) or (B) was delivered via stop-flow method for intracoronary infusion. The primary efficacy endpoint was change in resting myocardial perfusion measured by gated SPECT over 6 months. Ventricular function was also assessed (CMR). The primary safety endpoint was occurrence of AEs, SAEs and MACE (CV mortality, heart failure, reinfarction, revascularization).
Results: 161 patients were randomized and received intracoronary infusion (from Jan 2012 to Dec 2013). Mean age was 57.3±10.6, 81% were men and minority had history of HF, prior MI or DM (12%, 17%, 27%, respectively). LVEF by CMR was 36.5±9.1. The 6-month data will be presented.
Conclusions: PreSERVE-AMI represents the largest study of cell-based therapy for STEMI completed in US and will determine endpoints, sample size and suitability of autologous CD34+ cell therapy for upcoming Phase 3 study in patients with LVD post STEMI who are at risk for death and major morbidity.
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At 161 randomized patients....more than any CYTX cardiac studies combined.
I still ask why can Cytori not enroll ???????????????????????????????????????????????
I believe this is a MAJOR question that needs to be answered if we think this tech is going forward for Cytori

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Abstract from NBS board 17 Nov 2014 16:31 #2700

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Statistically significant mortality benefit observed in patients with acute myocardial infarction (AMI) treated with intracoronary administration of CD34 cells (NBS10; AMR-001) as well as statistically significant relationship between higher cell doses and improvement in ejection fraction and reduced incidence of serious adverse events and a dose-dependent numerical decrease in major adverse cardiac events

Conference call scheduled for Tuesday, November 18th at 8:00 AM EST

NEW YORK, Nov. 17, 2014 (GLOBE NEWSWIRE) -- NeoStem, Inc. (NBS), a biopharmaceutical company developing novel cell based therapeutics, today announced initial positive data from its 161 patient Phase 2 PreSERVE AMI (or acute myocardial infarction) clinical trial. These data are based on all enrolled patients being treated and having received six month follow-up for imaging and twelve month median length follow up for mortality, adverse events, serious adverse events (SAEs) and major adverse cardiac events (MACE).

Highlights of the initial results include:

A statistically significant mortality benefit (p<0.05) in patients treated with NBS10 (also known as AMR-001) as compared to the placebo group; there were no deaths in the treatment group.
A statistically significant dose-dependent reduction in SAEs (p<0.05).
Observation of a dose-dependent numerical decrease in MACE. MACE occurred in 14% of control subjects, in 17% of subjects of who received less than 14 million CD34 cells, in 10% of subjects who received greater than 14 million CD34 cells, and in 7% of subjects who received greater than 20 million CD34 cells.
When correcting for the time to stent implantation in all subjects, patients treated with CD34 cells were seen to have a statistically significant dose-dependent improvement in their ejection fraction (p<0.05). Independent from time to stent implantation, a statistically significant improvement in ejection fraction (p<0.05) for patients treated with a dose of greater than 20 million CD34 cells compared to placebo was observed.
No meaningful difference in perfusion, as evidenced by SPECT imaging, between the treatment and the control group from baseline to 6 months in resting total severity score (RTSS) suggesting this may not be a future suitable tool to assess NBS10, which is consistent with U.S. Food and Drug Administration (FDA) guidance that mortality and MACE are the appropriate approvable endpoints to determine efficacy of a cellular therapy for cardiac disease as opposed to imaging endpoints.
"For cardiologists, our key goal is to keep patients from progressing to worsening heart muscle function and death after a major heart attack," said Dr. Arshed A. Quyyumi, Professor of Medicine at Emory University and Lead Principal Investigator of the PreSERVE AMI study. "It is encouraging to see clinically meaningful results this early in the study, and I look forward to future data readouts."

Interestingly, prior to trial enrollment, patients subsequently randomized to the treatment group had experienced a significantly longer time to stent implantation after the onset of symptoms (931 minutes) compared to subjects subsequently randomized to the control group (569 minutes). This longer interval to reperfusion would ordinarily be expected to be associated with worse clinical outcomes.*

Further supporting the potential efficacy of this product candidate, the results provide evidence that the positive effects observed were due to intracoronary administration of NBS10, and not endogenous CD34 cells. There was no relationship between high bone marrow CD34 cell counts and improvements in MACE, mortality, or ejection fraction in the control group.

"Similar to what was seen in Phase 1, we have observed a relationship between the dose of CD34 cells administered and a positive effect on cardiac function. In our current trial, in addition to improved cardiac function, a CD34 dose-related reduction in serious adverse events was observed, highlighting the potential for clinical benefit," said Dr. Andrew Pecora, Director and Chief Visionary Officer of NeoStem and co-inventor of the core technology upon which NeoStem's Ischemic Repair Program is based.

Dr. Douglas W. Losordo, Chief Medical Officer of NeoStem, stated that, "the demonstration by this study of a statistically significant reduction in mortality and a dose-dependent reduction in overall MACE in treated subjects provides us important direction as we move towards designing a pivotal trial that is consistent with FDA guidance."

NeoStem's subsidiary, PCT (Progenitor Cell Therapy), a leading contract development and manufacturing organization in the cellular therapy industry, developed the manufacturing process for NBS10, and has provided all of the manufacturing of product for both its Phase 1 and Phase 2 trials. Over the last two years, PCT has worked to further optimize the yield of CD34 cells in order to maximize the dose that can be delivered to patients.

"By refining the methods for collecting and purifying CD34 cells for the PreSERVE AMI trial, we believe that we can facilitate providing doses of a sufficient number of CD34 cells for most patients from a single harvest," said Dr. Robert Preti, NeoStem's Chief Scientific Officer, President of PCT, and co-inventor of the core technology upon which NeoStem's Ischemic Repair Program is based. "The Engineering and Innovation Center at PCT continues to refine the process to provide for high quality, scalable and sustainable manufacturing at an optimal cost of goods for wide-scale commercial production."

Patients with AMI are at significant risk of downstream adverse events, including chronic heart failure, recurrent AMI, significant arrhythmias, premature death or acute coronary syndrome. A report from Agency for Healthcare Research and Quality (2011) surveyed the most expensive hospitalization conditions by payor, and lists AMI as the sixth most expensive condition treated in U.S. hospitals, with a national hospital bill of more than $37 billion annually.

"Heart attacks and cardiovascular disease are a significant physical and economic burden on society, and it is encouraging to see what we believe to be a meaningful impact on patient outcomes at this early point in the trial," said Dr. Robin Smith, Chairman and CEO of NeoStem. "While perfusion is important in the pathophysiology of a damaged heart, SPECT imaging may not be sensitive enough to measure differences. Additionally, the FDA has taken the position that such analysis should not be relied upon as an "approvable" endpoint for a cellular therapy for cardiac disease. As we continue to develop NBS10, we will continue to consult with the FDA, external advisors and future partners to determine the best path forward for the future."

As previously announced, the Company plans to conduct an investor conference call and webcast relating to the data tomorrow, Tuesday, November 18th, at 8:00 AM EST. Visit the Company's website at www.neostem.com/investors/investor-events to access the webcast or call 1-855-235-8282 and provide Conference ID 32811273.

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Abstract from NBS board 18 Nov 2014 07:17 #2703

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Obviously the primary end point were not reached- from clinicaltrials.gov

Primary Outcome Measures:
To determine safety and the effect of intracoronary infusion of AMR-001 on myocardial perfusion (RTSS), measured by gated SPECT MPI at baseline and six months in subjects post-STEMI [ Time Frame: primary outcome measured at 6 months ] [ Designated as safety issue: Yes ]
primary endpoint includes safety of bone marrow procurement (measured by adverse events) and AMR-001 cell infusion (including incidence of re-stenosis and stent thrombosis in addition to other adverse events)as well as efficacy measured by quantitative by gated SPECT MPI specifically looking at resting total severity score)


MACE or mortality at 6 or 12 months to me is not saying all that much- especially if control has very very low rates of 14% for MACE :really:

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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. :cry:

Abstract from NBS board 18 Nov 2014 09:40 #2708

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Agree Fas but I still am curious on Cytori's enrollment issues.

NBS had a 1:1 randomization in this trial ...so they treated about 80 patients...more than ADVANCE,APOLLO, PRECISE and ATHENA combined !!!

I know they stopped ADVANCE, APOLLO and PRECISE early...but they still had extremely slow enrollments in those trials.

I am still not satisfied what the problem is with enrollment rates.

BM is no cake walk and off the shelf treatment of a strangers cells I would think would also cause some concerns among some.

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