NeoStem: Understanding Research And Its Implications To Clinical Trials

Sep.18.13 | About: Caladrius Biosciences, (CLBS)

On September 11, a report published in the European Heart Journal Advance Access essentially validated the workings of NeoStem's (NBS) Phase II AMR-001, or at least the approach that NeoStem is using. The report flew somewhat under-the-radar, because a few days later, a negative article on Seeking Alpha questioned AMR-001, and caused NeoStem's stock to fall drastically. As a result, I reached out to NeoStem's Chief Medical Officer and CD34+ cell specialist Dr. Douglas Losordo who clarified the controversy quite nicely and completely tore down the author's argument in this Instablog post.

However, the report in European Heart Journal was quite important to NeoStem, yet no one seemed to notice. One reason is likely because these research reports are written in a way that very few retail investors (or analysts) can understand. Therefore, once more, I reached out to the company, hoping that this seemingly positive research report can be summarized for investors to understand. Hence, here is a short Q&A with the company's PCT segment's CMO Dr. Andrew Pecora, and his take on the report.

Note: I have added a few notes (in bold) for clarification and for important points.

Nichols

How do the results of this study compare with other related studies that have released either final or interim data? From a size, safety, and efficacy point of view.

Dr. Pecora

Pretty much the same. All studies have shown that if an adequate number of CD34 cells are administered (either isolated or admixed with marrow) during the window phase after inflammation has subsided (days 5-12 post acute myocardial infarction (AMI) there is a consistent finding of increased LVEF, preservation of heart muscle function and less adverse remodeling. One study also showed significantly fewer clinical events. (Essentially, Dr. Pecora is saying that when trials are done correctly, and the threshold dose is used, the outcome is consistent, which also goes hand-in-hand with NeoStem's goal in its Phase II trial)

Nichols

Can you elaborate on the significance of this statement within the research report?

"There was no difference in LVEF improvement between patients treated with cell infusion ,7 days from primary PCI compared with ≥7 days (1.46%, 95% CI: 0.41 to 2.51 vs. 2.69%, 95% CI: 1.80 to 3.58, P 1⁄4 0.08). Furthermore, we found no difference in LVEF improvement comparing patients with number of injected mono- nuclear BMC of ,108 compared with ≥ 108 (2.80%, 95% CI: 0.79 to 4.80 vs. 0.58%, 95% CI: 20.44 to 1.59, P 1⁄4 0.05), Table 2. Studies, using MRI as LV function assessment had a smaller treatment effect in LVEF when compared with non-MRI studies (0.16% 95% CI: 20.88 to 1.20 vs. 4.67%, 95% CI: 3.69 to 5.66, P, 0.001)."

Dr. Pecora

This is a meta-analysis so data of this kind will not pick up small differences and probably cannot be used to conclude this fine a point. In regard to the days post PCI we know there is no difference in effect if cells are given day 5 vs. day 8 but there is no effect if given day 3 so one would need to know how the actual day of delivery is weighted in the cut they did (the day administered is very important to outcome). There is no good correlation between the number of mononuclear cells infused which is irrelevant and the number of CD 34 cells which are a constituent of the mononuclear cells and the cells that cause the effect. In addition further confounding this analysis is that the more mononuclear cells infused the more cells there are to get in the way of the CD34 cells. MRI has less variability than standard echo and what is important is not effect size (i.e. how much the LVEF goes up) it is the percentage of patients that do not have a drop in LVEF that matters. What matters is preservation of heart muscle function (preservation of heart muscle function was shown, and is the goal of NeoStem's Phase II study).

Nichols

Can you expand on the importance of the trial size and impact it has on being able to analyze subgroup data?

Dr. Pecora

It is more than adequate for the general effect assessment and conclusion that bone marrow derived cells administered after an AMI via the coronary artery preserve heart muscle function and prevent adverse remodeling

Nichols

From an investor's perspective, what do you feel is the single most important take away from this report?

Dr. Pecora

In regard to AMR-001, in our study we are administering a much greater number of CD34 cells than prior studies and not admixed with mononuclear cells. In our study we have limited entry to patients with persistent cardiac dysfunction (LVEF <48% on day 4), which would indicate that most of our patients fall into the <40% category in this analysis (because the LVEF is taken before day 4 in these studies and tends to improve by day 4). Thus if an effect is observed in most studies used for this meta analysis than our study should result in a similar effect at minimum and could be greater because we are giving a greater number of potent cells to a sicker population.

Final Thoughts

Now, hopefully Dr. Pecora's response made this study easier to follow/understand. Unfortunately, retail investors tend not to pay attention to reports such as this, and only show interest at the end of Phase III trials when a study either "met" or "did not meet" primary and secondary endpoints. However, reports such as this can give you, as an investor, a better idea of future success, or a lack thereof. Then, you aren't as likely to respond to the daily volatility that is created with such stocks, and will feel better about your investment.

Disclosure: I am long NBS. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.