Hope for Type I diabetics

By John Pickering 23/11/2012

Living Cells Technology have announced the beginning of phase II trials of their product for helping Type I diabetics (they call it DIABECELL).  The idea behind the technology is to inject cells (called islet cells – normally present in the pancreas) that can sense glucose levels and release insulin.  LCT has managed to isolate these cells from pigs and encapsulate them in a way that the body’s immune system will not react to them – no anti-rejection drugs necessary.  Being xeno-transplant it has gone through quite a process even to get to the stage of Phase I trials.

This is pretty cool and I sure hope it all works out.  A Phase I/IIa (safety trials and first stage efficacy trial aimed to find an optimal dose) has been conducted at Middlemore hospital in New Zealand and another is underway in Argentina.  A press release in September announced the success of the Middlemore trial:

The New Zealand dose-finding trial was led by Dr John Baker at Middlemore Hospital in Auckland and saw 14 patients treated with a single implant of DIABECELL at doses of 5,000, 10,000, 15,000 and 20,000 IEQ/kg (islet equivalents per kilogram of body weight). The trial demonstrated that DIABECELL is a safe and effective treatment which results in: 

  • a statistically significant reduction in unaware hypoglycaemic events at doses of 5,000 and 10,000 IEQ/Kga
  • trend to reduction in HbA1c
  • improvement in patient-reported quality of life 

Note – HbA1c is just a form of haemoglobin (from the blood) proportional to the blood plasma glucose concentration.

Positive preliminary results from the 9 person Argentina based Phase I/IIb trial were announced.  The difference from the NZ trial is that two doses were given 12 weeks apart.  Followup has not been complete.

While this is all good news, I see no indication that the research has been peer reviewed (nothing in the Press release and I looked on PubMed as well).

The announcement this week is of a phase IIb trial of 20 patients with a dose of 10 IEQ/kg.  The announcement mentioned the trial will be in Argentina with 20 patients.  This is a little different from a September press release which mentioned 15 patients. The hope to metamorphosise the Phase IIb trial into a Phase III trial with an additional 10 patients from NZ.  A Phase III trial is to confirm effectiveness and monitor side effects – it is intended as the final step before regulatory approval.

In the press release the CEO announced.

“We remain on track to meet our goal of completing clinical trials of DIABECELL by 2015 and having a product commercially available by 2016.”

When I read this I thought “gulp – that is pretty positive given trials have yet to be completed.”  I gulped twice when I realized the trials to date have yet to be peer reviewed (although some results are public).  My third “gulp” is that these trials are all in small numbers – especially the planned Phase III trial.  That is not to say that I have any suspicions about the results or the technology, merely I worry about the juxtaposition of “completing clinical trials” and “commercially available” without the explicit interim statement of “and if the product is shown to be safe and effective.”

Tagged: Clinical trials, DIABECELL, insulin, islet cells, living cell technologies, porcine, Type I diabetes

0 Responses to “Hope for Type I diabetics”

  • Cool, I wrote about this back in 2008 when the trial was starting. Good to see that it seems to be going well.

    I assume that the fairly dramatic impact of the treatment offsets the need for large numbers in the trials?
    Seems a bit scant going from 9 patients to 20 patients and then to 30. I would have thought obtaining large numbers wouldn’t have been a problem. According to Diabetes NZ there are 15,000 people with type I diabetes in NZ alone.

  • My daughter has type one so I follow trials like these with great interest. From memory I think that they only trialled this treatment on patients that were suffering severe complications as a result of their diabetes. I think that this may be do to with the ethical issues of trialling therapies on otherwise healthy people. I was wondering if any one knows about the selection process and why they also used Argentina as a trial country.

  • This is a small New Zealand company with an innovative expensive technology in a rather contentious area – they needed permission from the New Zealand Minister of Health to even start trials here. It’s a constant trade off between size of trial, cost, need to meet investor milestones, regulatory demands and so on and so on. This isn’t a multinational with billions to invest in the definitive trial straight up.

  • Hi George
    They have had $50m or so invested. While trials are expensive I would not have thought a trial of a couple of hundred patients would have cost more than a couple of millions (I was involved in an expensive ICU trial of >500 patients which cost about 1.5M). Philosophically speaking there should never be a trade-off in having sufficient numbers to demonstrate efficacy.

    Having said that the Phase III trial outcome is a difference in the Hb1Ac levels. They are recruiting patients with levels between 7 and 10%. The normal range is 3.5 to 5.5%. I don’t know what would be a clinically significant change, maybe only a 1% fall? If, assuming the standard deviation of the difference between before and after Hb1Ac levels was also 1%, then only 15 subjects would be needed for a typical trial (alpha=0.05, power=0.95). This is low because each patient acts as their own controls.
    I noted they are also limited to those with severe metabolic instability – this limits the potential recruitment.