Data From American College of Cardiology: $NBS, $BAX, $ASTM, $CMXI

Data came out over the weekend in Advance of the American College of Cardiology meeting in Chicago. The article reviews the Focus-CCTRN trial which uses autologous bone marrow to treat heart disease in a Phase II trial.  Specifically the trial evaluates the injection of bone marrow in ischemic cardiomyopathy.   This trial is similar to what Baxter is working on in their phase III trial using not bone marrow but what they believe is the active cell in marrow, CD 34+ cells. Incidentally this is similar to what NeoStem is doing with the Phase II Amorcyte Heart Attack “PRESERVE” trial which is using IRA (Infarct related artery) injection of CD 34+ cells (NeoStem is also doing the manufacturing for Baxter).
 
The results of the study are fascinating. They showed that the greatest efficacy was shown in those patients who received the greatest number of CD 34 cells.
 
Specifically the article states: 

"A regression analysis showed that higher CD34 cell or CD133 cell counts were associated with greater absolute unit increase in LVEF. The range of CD34 was 0.5% to 6.9% (SD, 1.2%). Assuming that differences of 1.96 for SD or 2.4% are more likely due to biological variability, the effect of differences in CD34 cell level beyond that expected due to natural variability was examined, using a 3% level to be conservative. Every 3% higher level of CD34 cells was associated with on average a 3.0% greater absolute unit increase in LVEF in a multiple variable model that included age and treatment as predictor variables (3.06 [95% CI, 0.14-5.98];P=.04)."

This article seems to confirm what NeoStem’s Chief Medical officer, Andrew Pecora MD, and Phase II Trial Investigator, Arshed Quyyumi MD, FRCP wrote in their Letter to the editor (Published in JAMA, March 14, 2012) that reviews the results from another Bone Marrow Trial (The Late TIME trial) that was presented last Fall at the American Heart Association (AHA).

“In the Late TIME trial, treated patients received a median CD34 cell dose of 3.8±1.5x106 cells, well below 10x106 CD34 cells. Additionally, in vitro SDF-1 mobility of the infused cells was not measured and may have been adversely affected by the absence of autologous serum in the infused product. Future studies must account for the quantity and mobility of infused (potent) cells before conclusions regarding efficacy are made.”

Daily Dose Conclusion: A lot of work has been done with Bone Marrow cells and its all shown trends but there have not been any home runs. The data seems to be pointing to the active ingredient (there may be more than one, that’s for sure) is CD 34+ cells. Patinets with greater numbers of these cells  are showing efficacy. The Amorcyte Phase 1 data was very compelling showing a statistically valid correlation between the number of CD 34 + CXCR4+ cells and the effect on both perfusion and infarct size. The fact that Baxter is also pursuing a CD 34+ cell approach is validating. The trial is being run by Dr. Doug Losordo  who is considered a Key Opinion Leader (KOL) and Pioneer in cell therapy. Dr. Losordo’s team last summer published the results of experiments that showed that among all the various cells present in marrow, it is the CD 34+ cells that generate the greatest amount of blood vessel growth.

Daily Dose Equities - Effect of Transendocardial Delivery - CCTRN TrialThis article showed in a sub-group analysis that patients with higher numbers of CD34+ cells did best.

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Daily Dose Equities - Exosomes from Human CD34 + Stem Cells

This article is published by Dr. Doug Losordo, who since the article was printed, has joined Baxter to run their CD 34+ Cardiac Ischemia Trial (Angina – heart pain).

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Daily Dose Equities - Intracoronary Bone Marrow

Two Letters to the Editor of JAMA; 1) Dr Hung Q Ly MD, MSC, FRCPC and 2) Drs. Arshed Quyyumi and Andrew Pecora (NeoStem) discuss the flaws in the LATE-Time trial.

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Key markets covered include:

• Stem Cell Research
• Cardiac Heart Repair
• Benefits of using your own cells
• Stem Cell Trials
• Heart Attack Cell Therapy
• Proof of Concept
• Clinical Trial Data

JAMA: Letter to the Editor : Intracoronary Bone Marrow Mononuclear Cells After Myocardial Infarction

We picked up on a JAMA letter to the editor (below) that reviews data from the TIME trial that was presented last fall. The author, Drs Arshed Quyyumi (NeoStem PI) and Andrew Pecora (NeoStem CMO) clearly identify that the effective dose given in the "Late TIME" trial appears to have been low , (3.8 million CD 34 cells) versus data that the Amorcyte trial reported that an effective biological threshold exists at 10 million cells. The authors in the letter to the editor state:

In the LateTIME trial, treated patients received a median CD34 cell dose of 3.8±1.5 x106 cells, well below 10 x106 CD34 cells. Additionally, in vitro SDF-1 mobility of the infused cells was not measured and may have been adversely affected by the absence of autologous serum in the infused product. Future studies must account for the quantity and mobility of infused (potent) cells before conclusions regarding efficacy are made.

Daily Dose Conclusion: NeoStem (NBS)  and Baxter (BAX) are both pursuing the use of CD 34+ cells in STEMI and CMI (angina) respectively. CytoMedix just reported that ALD-br cells show hints of efficacy and Aastrom seems to be moving forward in DCM. All cardiology indications. The NeoStem message is focused on the dose, timing and method of delivery, biological effect and clinical outcome. We see this as a core strength and part of what Progenitor Cell therapy (PCT) brings to the company.

On a separate note we believe Cardiology is the next major breakthrough to be seen in the regenerative medicine space. While NeoStem is well positioned as a manufacturer for Baxter and their own Amorcyte the company also has attractive valuation measures. That is not to say that other players like Aastrom , Athersys and Cytori are likely to move forward with P2/3 plans in the cardiac care space. Also keep an eye out for MesoBlast which has seen a decline in valuation since the TIME (& their own data) was presented at AHA last fall.

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Intracoronary Bone Marrow Mononuclear Cells After Myocardial Infarction

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