Stem cell therapy of type 1 diabetes – recent failed trials

by Alexey Bersenev on November 4, 2012 · 1 comment

in Uncategorized

Results of 3 clinical trials, assessing stem cell therapy for treatment of type 1 diabetes, were reported during last year as failed. I’ll go through the trials in this post.

1. Osiris trial
At the beginning of the year, Osiris Therapeutics reported results of Phase 2 trial, assessing Prochymal in type 1 diabetes. The trial is multicenter, randomized, double-blind and placebo-controlled with 60 patients enrollment. Type of cells – allogeneic, unmatched, bone marrow-derived mesenchymal stromal cells, expanded ex vivo.

The results were disappointing and trial considered as failed. Unfortunately, 1-year follow-up interim results were reported only in company’s press-release and we can’t get more detailed information at this point. The trial’s interim results didn’t meet primary end point – C-peptide AUC response. There was no difference with placebo:

No significant differences in the rates of disease progression, as measured by stimulated C-peptide levels at the one year time point, have been observed. However there was a trend towards fewer hypoglycemic events for patients treated with Prochymal as compared to controls. The patients will be followed for another year (for a total of two years), after which time a complete analysis of the data will be conducted.

Biotechnology analyst @adamfeuerstein wrote:

Osiris notes a “trend” towards fewer incidences of low blood sugar reported by Prochymal-treated patients compared to those treated with a placebo at one year. What Osiris doesn’t say is that having something vaguely positive to report about one of six secondary endpoints matters not at all when the study’s primary endpoint fails.

2. U of Florida trial
Juvenile Diabetes Research Foundation (JDRF) and University of Florida have assessed the efficacy of autologous cord blood transplantation in adolescents with type 1 diabetes. This is single center, randomized open label trial with enrollment of 15 patients. The results were published here and here. The study didn’t meet primary end point of efficacy – favorable C-peptide level:

Autologous UCB infusion in children with T1D is safe and induces changes in Treg frequency but fails to preserve C-peptide.

The authors indicated that efficacy assessment is difficult, because study design didn’t include control group. Placebo control was not allowed by FDA and IRB. It begs the question of proper design of clinical trials, involved autologous cord blood, stored in private banks. The other possible reasons of failure:

The reasons for an inability of autologous UCB to effectively halt autoimmune progression are at least twofold. First, an insufficient number of cells carrying regenerative or immunoregulatory capacity may have been transferred to patients with T1D. In addition, the ongoing autoimmune response in new-onset T1D subjects may contain memory T cells, refractive to regulation by Tregs (6), that facilitate the ongoing autoimmune destruction of endogenous or de novo β-cells.

To address the first issue, JDRF has initiated another trial in different site. JDRF also released a statement:

JDRF cannot encourage UCB storage for therapeutic purposes at this time given the lack of current clinical data demonstrating efficacy of UCB in preserving or restoring c-peptide in patients with type 1 diabetes.

3. Iranian trial
This week, a group from Tehran University reported results of Phase 2 trial, assessing allogeneic fetal liver-derived hematopoietic stem cells in both – type one (n=30) and type two (n=26) diabetes. The study was placebo-controlled.

In the 6th month of the follow-up, there was a significant decrease in HbA1c levels in all groups without any rise in the fasting c-peptide. However, none of the precipitants transiently or continuously became insulin free in the first year after transplantation.

I was not able to find any additional information about this trial in databases, but I hope to read a paper when it will pop up on journal’s web-site.



With these 3 failures, as far as I know, we still don’t have any controlled randomized studies, which have been proved efficacy of stem cell transplantation for treatment of type 1 diabetes. Could be a number of reasons for these failures. But, probably, one of the most apparent reasons is selection of therapeutic cell type. It seem to me that use of autologous mobilized blood hematopoietic progenitor cells could yield better results. However, for this type of cell transplant, we have to take in account severe immune ablative conditioning before procedure. Earlier report from Brazil was very promising. This year, Chinese group also reported good outcome. Both studies were not randomized and not controlled. We are waiting future update from ongoing trials. If you have more information about updated results of these or other trials, please share in comments.

{ 1 comment… read it below or add one }

Thomas Ichim May 27, 2013 at 6:46 pm

Excellent and very useful summary Alexei !!! thank you so much

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