Below is my discussion of the three recent news items:
Living Cell Technologies Gains Additional Benefit From DIABECELL
LCT recently finished a phase-I clinical trial of seven people. A few patients had short periods when they did not need to inject any insulin, others required less insulin, and some people were not helped at all. The very best result was that one person was insulin independent for two months. So they took that person, and gave her another implant. This time her insulin requirement dropped 50%. They waited a few more months and gave her a third transplant. After this third transplant, she is again insulin independent. They don't say how long after the third transplant it has been. The first transplant was 5 ku/kg, the second was also 5 ku/kg, and the third was 8 ku/kg. Two key quotes from the paper are:
reports insulin independence in a patient with insulin dependent type 1 diabetes
At this early stage of clinical trials, results show that insulin independence is potentially achievable at least in some patients and that repeat implants are safe.My Thoughts on this Paper
It is important to remember that this press release discusses only a single person, so I'm very cautious about reading too much into it. Especially since this one person had the best results of all the people in the phase-I trial. She was the person who was insulin free for the longest period after the first transplant. So by publishing only her follow on results, they are really "cherry picking" their results. ("Cherry picking" refers to only including the people who had the best results, and ignoring the people who had other results. It can be a huge source of bias in scientific research.)
Keeping all that in mind, I think these results imply that the current LCT implant product is effective for less than 6 months, when given in the 5ku/kg dose. Here is my reasoning: for this patient, a dose of 8 ku/kg leads to insulin independence the one time it was used. But a dose of 5 ku/kg sometimes does and sometimes does not. But the second 5 ku/kg dose did not lead to insulin independence, which suggests that there was less than 2ku/kg cells still working from the first implantation. (Because if there was more than that, there would have been 8ku/kg total effective when he second operation was done: 3 left over from the first operation, and 5 new ones.) So that implies that the LCT implants don't last very long right now. That's not the end of the world, of course. LCT has years to improve these before they are approved for general use, but it does suggest that they have a long way to go, if people want a cure that only requires an operation every few years. Of course for those who will accept a cure that requires an operation every few months, that is much closer.
Put another way: This patient got a dose and went for 2 months without needing insulin, but then needed it again. Her second dose did not provide any insulin independence. If there were still some working cells from the first implantation, then they would have combined with the new cells to give insulin independence again. But that did not happen.
A note on the Politics of this Information
The most important thing about this press release, is that there is no new news here. The patient in question was "insulin independent" for two months, at the start of the phase-I trial (months ago), and is now "insulin independent" again (with no duration reported).
So why a press release now? My answer: Politics.
LCT has been working for almost a decade to get approval for human testing in New Zealand. Initially, they were questions about the safety of xenotransplantation (especially with respect to a particular pig disease called PERV). LCT did a lot of safety based research, and put those questions to rest years ago, but still New Zealand refused to allow clinical trials. Finally, LCT moved ahead with clinical trials in Russia, which were successful. New Zealand was finally shamed into approving the clinical trails "conditionally" on LCT getting some scientific safety approvals. That wasn't a problem, because LCT has had solid scientific safety studies done for years. They got the approvals, and the New Zealand political minister still has not approved their testing. Hence the press release.
The only good news is that LCT is (or was, see below) also working toward starting a phase-II trial in the US mid this year, and that should happen independently of New Zealand.
Living Cell Technologies Welcomes Report On Safety of Pig Cell Transplants
Here LCT publicizes research done by others. One of the fears of LCT's treatment is that a pig retrovirus might infect people via the transplant. This is especially true of very hard to detect retrovirus, such as PERV, which is similar to retroviruses which are known to cause incurable diseases in sheep, cows, and humans, and to jump from species to species.
LCT had previously done studies to show that the pigs in their flock did not have PERV, and that PERV could be detected prior to transplantation, and that PERV in the beta cells was unlikely to be transferred to people who got transplants, even if in the pigs. So they had already show a solid three barrier safety infrastructure.
Here they report on research were several types of non-human primates were injected with PERV and other viruses and non-virus pathogens found in pigs, after the primates had been injected with drugs specifically to weaken their immune system. None of the primates got sick. That is pretty much the ultimate safety testing. It shows that even if all the safety systems break down, and PERV go straight into a person, and the person has a very weak immune system, then they still will not get sick.
This is good news, and should put to rest any lingering worries about PERV safety in LCT"s treatment.
From the "Note from the CEO" column in the March 2009 LCT Newsletter:
LCT has been in discussions with advisors in Russia to outline a commercialisation route and business plan. To focus on this commercialisation plan, Dr Robert Caspari stepped down as CEO as activities in the United States are of lower priority. Dr Caspari remains a valued member of our board of directors.Also, there is no mention in this newsletter of the previously proposed, larger scale, clinical trials to start at the Barbara Davis center in Denver, USA.
Some people have interpreted this to mean that the larger phase-II trial they had been talking about running in the US has been put on hold in favor of more work in Russia. Obviously that would be disappointing to people in the US who were hoping to take part in the trial.
Also, if they can not resolve their differences with the New Zealand minister, and can't get started in the US, that leaves only their Russian testing. I'm also worried about the impact of "all Russian" clinical trial data on future US FDA approval. Officially, I think the FDA treats well done clinical trial data the same, no matter where it was done. But I'm a little worried that unofficially, having nothing but Russian data may delay things.
I hope that this entire interpretation is wrong (ie. they are getting rid of their American CEO, but that will not impact their American clinical trials). That would be the best news. They wanted to start that trial mid-2009, so we should know soon if there is a delay.