Cell therapy clinical trials failures in 2014

by Alexey Bersenev on January 4, 2015 · 4 comments

in Uncategorized

Today, I’d like to highlight the most interesting, in my opinion, clinical trials failures, reported in 2014. As field is moving to efficacy (Phase 2) trials, we are starting to see more failures. In this overview, I’m going to focus on efficacy results. I hope we can learn a lot from these failures and avoid mistakes in designing new trials in the future.


1. MultiStem fails in Phase 2 ulcerative colitis trial
This year, US-based company Athersys announced results of stem cell product MultiStem infusion in patients with ulcerative colitis. The trial failed to meet efficacy end points in interim analysis – there was no difference between MultiStem and placebo groups. The trial was conducted by Pfizer in US, Canada and Europe.

2. Results of Miltenyi’s Cardio 133 trial
Unfortunately, all cardiac cell therapy trials, sponsored by Miltenyi Biotec and involved purified CD133+ cells, are failing. In 2013, the company terminated its Phase 1 CABG trial, due to lack of recruitment. Cardio 133 Phase 2/3 randomized placebo-controlled trial was assessing autologous CD133+ bone marrow-derived cells in ischemic heart failure. The trial was completed in 2011, but results were released to public this year. Cardio 133 failed due to lack of efficacy – cells were not different from placebo.

3. Allocure terminates ACT-AKI trial
Phase 2 trial, conducted by AlloCure, which assessed mesenchymal stromal cells in acute kidney injury, was terminated in August due to futility. The trial started in 2012 with enrollment target 200 patients. There was no official information from the company, but some results and decision to stop a trial were reported on conference – look here and here.

4. Indian stroke trial
Results of ischemic stroke trial, which assessed efficacy of autologous bone marrow mononuclear cells, were recently published. It was randomized, multicenter controlled trial with n=120. The trial failed all end points – there was no difference between cells and control group. Trial was sponsored by Manipal Acunova.

5. Post-marketing approval trial of Korean “stem cell drug” HeartiCellGram-AMI
In July of 2011 South Korean company FCB Pharmicell got marketing approval for the world’s first stem cell product for myocardial infarction – HeartiCellGram-AMI. According KFDA, company continues to conduct clinical trials to demonstrate efficacy and reports o agency. The results of Phase 2/3 trial, assessing HeartiCellGram-AMI in myocardial infarction, were recently published. It failed! Secondary end points were missed, but also primary endpoints were not different between “cells” and “placebo” groups. If you look at table 4 – global LVEF by SPEC at 6 months in MSC group =55, in placebo group =53.9. It is unclear how KFDA will react and how it will affect sales of the drug.

6. Adipose MSC failed in ARDS
Small Phase 1 trial in China was testing allogeneic adipose tissue-derived mesenchymal stromal cells (MSC) in acute respiratory distress syndrome (ARDS). Researchers randomized 12 patients in experimental and placebo control groups (6 patients per group). Unfortunately there was no any clinical difference between “cells” and “placebo” groups. Even though, trial was underpowered to assess efficacy properly, the authors more likely will not pursue the same strategy.

7. CD133+ in CLI is not feasible
This trial is a rare example of feasibility failure. Results of randomized, double-blind, placebo-controlled trial, assessing autologous mobilized CD133+ cells in critical limb ischemia (CLI), have been published. Unfortunately, trial was halted, due to lack of feasibility. And the reason is inability to achieve “the pre-specified minimum mobilized cell dose threshold” equal 50 millions of CD133+ cells. Only 3 of 10 patients passed this threshold. The obvious lesson – don’t use mobilization protocols to collect CD133+ cells from periphery.

8. MSC failed in multiple sclerosis
Spanish Phase 2 trial assessed long-term safety and efficacy of autologous bone marrow-derived expanded MSC in multiple sclerosis. The authors reported 9 patients only (5 in MSC group and 4 in placebo), but efficacy end points were missed. I’m not sure how they got an approval with n=9 for efficacy assessment. Failure 2-folds!

9. Chinese diabetes trial
Autologous mobilized blood-derived mononuclear cells were used (as hematopoietic graft) in children with newly diagnosed type 1 diabetes. 14 patients received cell therapy and 28 patients were assigned as control. At 3-5 years readout, there was no advantage in cell therapy group in terms of insulin dose and glucose control.

10. Stempeucel failed efficacy in AMI
One more commercial cardiac cell therapy trial. Indian company Stempeutics Research assessed allogeneic bone marrow-derived expanded MSC in acute myocardial infarction (AMI). The results of the trial indicate that there was no difference in LVEF and perfusion between groups. Even though, product candidate demonstrated good safety profile, company should work on better design (efficacy end points) of future trials.

These are some highlights of the year. Of course there were more failures, but I was trying to pick the most interesting cases. I’ll add few more in the comments to complete the picture. Please contribute to the list of failures in comments!

{ 4 comments… read them below or add one }

Gordon Beck January 5, 2015 at 8:43 am

Alexey, the Athersys trial showed efficacy at 4 weeks. There was a difference between Multistem and Placebo at that point. What failed was the trial design. There was only one does given. There should have been multiple doses and at higher amounts. Pfizer is still partnered with Athersys and are preparing for a redesign for this trial.

Also, I anticipate positive results from the current ischemic trial Athersys is running. (Double blind, placebo controlled, n=140) A lot of companies are failing, but I don’t think Athersys will be one of them. They are poised to change the way people view regenerative medicine.


Vlad January 7, 2015 at 4:02 am

Hi Alex.

“If you look at table 4 – global LVEF by SPEC at 6 months in MSC group =55, in placebo group =53.9.”

I also see at table 4 – LVEF by SPECT at 6 month was greater in MSCs group than in the control group (5.9% vs 1.6%, P=0.037). Do you think it is not enough for the success of research??


Barry Li January 20, 2015 at 4:54 pm

Yes, I believe that. Currently, most of stem cells are not focusing on cell engineering work such as cell survival curve and so on (which is meaning the cell dynamic situation in vivo after treatment). When I visited stem cell lab in China and USA, a lot of stem cell persons only have about 10 years experiences. Stem cells are very diverse to culture, if you have not experiences regarding culture more than 100 set of stem cell culture, all results are not feasible.



John garcia October 13, 2015 at 2:24 pm

Dr. Gionis,

I spoke with you some time back regarding stem cells being used in ulcerative colitis. Since then my brother did a clinical trial with Athersys, using there MultiStem experimental treatment. I am not sure why the clinical trials were deemed a failure, and the stock dropped. Now Athersys is doing another clinical trial on stroke victims with a similar product…very odd.

The only think I can figure is that the stroke trial will bring in a larger investing crowd then the colitis cure – Because the MultiStem did, in fact, work, for my brother and several others that were in the double blind study. For 3 years after the study he was able to eat normal food without the horrible effects of the disease. For a decade prior he could never eat even a drop of chocolate or coffee, after treatment this was added to his diet with, shockingly no negative effects. Well as you may know the MultiStem is not a true homogeneous stem cell made from his body (in fact we do not know if his stem cells would even give such results).

Is it possible for you to administer, obtain or located the same MultiStem that was used in his clinical trials in Miami? Made by Athersys? Do you know anything about this MultiStem®, a patented, adult-derived “off-the-shelf” stem cell product platform, for multiple disease indications in the areas of neurological, cardiovascular disease, inflammatory and immune disease, as well as other areas.We have currently six clinical stage programs ?

I did try to call your office, but your phones went from an answering machine to 3 stages of automatic transfer then cut me off. I hope you are able to give some directions and may find some answer as to why this product was documented as a clinical trail failure, when it was not a failure at all.

This is the result of a random internet search for people who did the MultiStem trial – IT WORKS


“So I’ve been to this site many time researching things about UC but I’ve never posted before. However, after taking part in this Multistem trial I feel a duty to say something to others who are suffering about the excellent response I’ve had thus far in this trial. Long story short I was diagnosed in 1999 and been thru sulfasalazine, all mesalamine forms, VSL #3, prednisone, and Uceris and all had stopped responding. I was continuing to get really sick and didn’t want to go on Remicade or Humira because I think they are pretty scary drugs and I’m still really young. So I researched the Multistem trial for the clinical trials.gov website. I went through the screenings, was a candidate and had a 50/50 shot of having the Multistem stem cell infusion back in August. I was rated a 12 mayo score then. I’m confident I received the Multistem because I have slowly improved every day and am pretty sure I’m in complete remission now (I go back in two weeks for another look see). At any rate, I encourage any of you who are suffering and not being helped by the drugs we have available to us to check into this trial. Let me know if there are others of you having any results with this trial please.”


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