Cell therapy trials failures in 2013

by Alexey Bersenev on December 25, 2013 · 3 comments

in failure

At the end of the year, I want to bring your attention to major failures and setbacks for cell therapy field in 2013. This is an attempt to capture the vast majority of failed clinical trials. This overview is based on (i) results reported in literature (via PubMed) or (ii) companies press releases and (iii) updates from NCT registry record. The value of failures among all reported results is very low for Phase 1. That’s why I focused on later stages – controlled randomized trials in phases 2/3.

1. Autologous cord blood transplantation failed in type 1 diabetes
In September, results of German phase 1 controlled trial, assessing privately banking cord blood in juvenile type 1 diabetes, were released. This trial was mirroring US-based study, which is failed earlier. I’ve written a post about this failure:

There was no impact on metabolic (C-peptide, insulin requirement) or immunological (auto-antibodies, T-regs, CD4/CD8 ratio) profiles. Negative results of both trials allow us to conclude that autologous CBT does not work in children with type 1 diabetes.

2. Miltenyi Biotec terminates cardiac cell therapy trial
In December, German company Miltenyi Biotec has terminated its cell therapy trial. The Phase 1 trial was assessing safety and feasibility of autologous bone-marrow CD133+ cells (selected on company’s device CliniMACS) for patients with chronic ischemic cardiomyopathy and CABG. There was no official press release, but recently updated record in registry indicated that trial was “terminated due the lack of recruitment”. The company was not able to enroll 23 patients since 2010.

3. IMUC dendritic cell vaccine failed in glioblastoma
In December, ImmunoCellular Therapeutics (IMUC) released results of phase 2 trial, assessing autologous dendritic cell vaccine in glioblastoma patients. The result are disappointing, because based on analysis of 117 patients, primary end points were missed. There was no difference between cells and placebo. Read detailed analysis here.

4. Aastrom halts phase 3 trial in critical limb ischemia
In March, company Aastrom announced termination of phase 3 trial for critical limb ischemia (CLI) – REVIVE. I’ve written analysis of this failure:

The major reason for REVIVE failure is a poor trial design. The secondary reason is financial and strategic business considerations. Apparently, the failure has nothing to do with safety and efficacy of Aastrom’s cell product Ixmyelocel-T.

5. Bone marrow cells failed in multiple cardiac trials
Bone marrow cells (mostly mononuclear cell population) continue to fail in number of trials for cardiac conditions. Taking in account recent scandal, this year was not good for this type of trials. One year follow-up from phase 2 of TIME trial was “the final nail in the coffin“. The next is phase 2 of SWISS-AMI – no improvement in heart function at 4 months follow-up. Mesenchymal stem cells (MSC) also failed in Chinese controlled randomized trial – no difference between cells and control. One serious adverse event was reported during cells injection. Finally, Iranian phase 3 trial, assessing autologous bone marrow-derived CD133+ versus mononuclear cells, did not reveal any difference in hear function between cells groups and control at 18 months.

6. Cytomedix halts stroke trial in phase 2
In September, company Cytomedix announced that RECOVER-Stroke trial will be stopped by the end of this year. Cytomedix acquired autologous ALDH+ cell-based platform from Aldagen and started phase 2 stroke trial in 2011. Halting the trial was strategic business decision, due to very slow enrollment. Read more here and here.

7. Mobilized hematopoietic cells are useless in alcoholic liver cirrhosis
Results of randomized controlled trial, assessing autologous mobilized hematopoietic cells in decompensated alcoholic liver cirrhosis, were published in January. There was no difference in liver function improvement between control (standard treatment) versus “cells” groups.

8. No benefit of SVF-assisted lipotransfer in breast reconstruction
Despite the big buzz about fat-derived stromal vascular fraction (SVF) in cosmetic and reconstructive surgery, very few controlled studies have been done so far. We still don’t have a valid reason for such excitement, because some trials actually are failing. The recent study, which appeared online in the summer, did not reveal any benefits of SVF-enriched versus water-assisted lipotransfer in reconstructive breast augmentation. SVF was isolated automatically by Celution system.

9. CellMed terminates CellBeads trial in stroke
German company CellMed AG (a subsidiary of BTG plc.) officially terminated CellBeads clinical trial in stroke this March. The reason is the following: “Need for improvement of study medication. Safety data collected sufficient. No further gain in knowledge expected”. Very fuzzy, but as a consequence the whole CellBeads program was terminated by BTG plc (maybe CellMed even does not exist anymore). CellBeads-neuro is encapsulated allogeneic MSC, gene modified with Glucagon Like Peptide-1).

10. Termination of multiple cancer immunocellular therapy trials
Multiple trials, involved gene-modified T-cells or dendritic cells were terminated in phase 1 this year. The list is following: JapicCTI-090932 (sponsored by Takara Bio, reason is not indicated), NCT01944709 (due to “disease progression”), NCT01204502 (due to “changes in clinical practice”), NCT01273181 (due to neurological toxicity), NCT01457131 (reason is not indicated).

Concluding remark:
In this brief overview I’ve mentioned 17 clinical trials, recorded as officially failed in 2013. Perhaps, some of these trials failed earlier, but I relied on the record update and publications. As you can see, many trials were terminated, based on multiple different reasons. Termination is equal of trial failure, because we will not get to know the answer about cells safety and efficacy. Some trials were completed and failed simply because “cells did not work”. I did not cover all failed trials and I did not mentioned any case studies. I’d estimate a total number of reported failed trials this year ~ 25-30. Please let me know if I missed something, so we can make statistics more valuable.

{ 3 comments… read them below or add one }

Iwona Grad January 13, 2014 at 3:50 am

It looks quite disappointing, it would be nice to see a list of trials that succeded


Alexey Bersenev January 16, 2014 at 11:37 am

Hi Iwona,
I don’t think it’s disappointing, but opposite. I compare it with Pharma/ Biotech failure rates and I see that cell therapy as new industry does much better. I cover almost all (or 70-80%) of failures from 2013 and I focused on Phase 2 design.
If cell therapy Phase 2 success rate will be 30-60% it will be so great! I don’t have number yet, but it’s doable.
I did not list all trials, which succeed, because there are so many! As I note in the post, almost all cell therapy trials pass Phase 1. I’d expect success rate for Ph1 >85-90%. I don’t have time to do analysis of all these, because I don’t have full time job. But I’d be happy if someone can do this analysis and show us statistics. I called for collaboration on this matter 2 years ago, but didn’t get any responses. You can track all of these reports yourself and share analytics or you can follow my tracking and use it for analysis.
I track almost all reports real time here – https://twitter.com/#!/CellTrials


Darrel Francis January 23, 2014 at 12:53 am

Dear Alexey and Iwona,

We are in fact working on such an analysis whose results will soon be available.

In our reading we have come against some puzzling stumbling blocks. Can any readers please help?

For example, there are some things that are difficult for us to understand about the C-CURE trial.

Q1a. What was the predefined primary efficacy endpoint on the clinical trials register?

Q1b. Where are the results of this in the paper? (We can see echocardiographic data but no radionucleide data)

Q2a. Focussing on the echocardiographic secondary endpoint data because this is all that seems to be available, what is the mean of the ejection fraction effect across the stem cell recipients in Figure 4?

Q2b. What is the mean ejection fraction effect given in the Abstract and Results?

Readers might benefit from the additional information provided in response to our queries:







We would be grateful for any help, which could be channeled via Alexey or this website.


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