Sunday, December 12, 2010

LCT Gets Commercial Approval In Russia!

I had not planned to make another blog entry until Jan-2011, but I felt that the following news was important, so made an exception.   Happy Winter Solstice everyone!

The official sound track for this blog entry is The Blur's "Song 2":  Woooo-hooooo!

LCT Gets Commercial Approval In Russia!

Background: LCT is developing an encapsulated pig beta cell cure for type-1 diabetes.
Called "Diabecell", it has pig beta cells encapsulated in a special coating.  The coating allows blood sugar in, and insulin out, but does not allow the body's immune system to attack the beta cells.  It also allows nutrients in and waste products out.  This allows the beta cells to naturally grow and to react to the body's sugar by generating insulin which goes into the body's blood system.  Meanwhile, the body's autoimmune attack can not target these beta cells, and you don't need to take any immunsuppression drugs (as you would for a normal beta cell transplantation).  Remember that for decades, diabetics injected pig and cow insulin every day, so the fact that they are transplanting pig beta cells instead of human beta cells should not make anyone nervous.  Different researchers have been working on this kind of system for decades, but LCT is the first group to get government approval for this sort of "bio-artificial" pancreas.

I completely understand that not everyone considers a bio-artificial pancreas to be a cure.  Some people think it is just a good treatment: a much better treatment that we have now.  I've written this blog entry from the point of view of someone who thinks that a bio-artificial pancreas that really works is a cure.  If you don't believe that, just replace the word "cure" with "better treatment" in your mind as you read this.

So What Does This News Mean: My understanding is this means LCT has approval to sell their Diabecells as a commercial medical treatment in Russia.  LCT already has a commercial presence in Russia, so I would expect that in the next few months we will see actual availability of the treatment there.  LCT has said that they are working with two different clinics in Russia. LCT thinks that in the second half of 2011, you will be able to fly to Russia (if you don't live there already) and get this treatment.

What can LCT's Diabecell Do Right Now: In my opinion, the current performance of Diabecell does not make it a cure.  They have reported on less than 16 people, and only 2 of them were insulin free for any length of time, and those two were insulin free for only a few months.  But don't underestimate LCT's Diabecell just because it is not a cure right now:  First, research is about doing more in the future than you are doing right now, and this may grow into a cure over time.  Second, this treatment almost eliminates very low blood glucose episodes, and that is a benefit even without being a cure.  For "brittle" type-1 diabetics, this might prove reason enough to get this treatment.


Just about every one of these discussion points could be expanded to a full blog entry, all by themselves.  I'm just trying to "hit the high points" here.  As you read this discussion, don't forget the central point: these guys have gotten farther along the path of encapsulated beta cells as a future cure of type-1 diabetes than anyone else.  They are the first people to get government approval for something that might, in the future, with some more work, cure type-1 diabetes (at least by my definition of "cure").

Edmunton Protocol vs. Diabecell
In a previous blog I compared Diabecell with Burt's immune system reboot research, but that was unfair because Diabecell works on established diabetics, while the reboot research has only been tested on honeymoon diabetics.  However, a better comparison might be to compare the Edmunton protocol (for beta cell transplants) to Diabecell (for encapsulated beta cell transplants).  Both work on established type-1 diabetes.  Unfortunately, I don't know exactly how successful the Edmunton Protocol is, as used these days, so I can't compare it to Diabecell.  But it would be a great project: a useful head to head comparison of cure rates and durations of these two transplant techniques.

My best guess is that right now, the Edmunton protocol has a much higher success rate (in terms of % of people who don't need to use insulin for some period of time) and a much longer remission rate (length of time they don't need to use insulin).  However, it requires the person to take immune suppession drugs for the rest of their life.  Those drugs have serious side effects, and taking them for years or decades raises the chance of problems in the future (like cancer), and Diabecell doesn't have those side effects.

But I do think that the first commercial impact that Diabecell is going to have is on the Edmunton protocol clinics.  Right now, only a few diabetics get an Edmunton protocol beta cell transplant.  The ones who do are often "brittle" diabetics who experience seizures and are either worried about driving, or worried about "dead-in-bed" or both.  Those diabetics will now have an alternative to the Edmunton protocol, and we will see over the next few years how many of them take advantage of it.

From Here to a Cure
One obvious question is, if the current Diabecell is not a cure, can they make it into one?  And if so, how long will that take?  I think there are two steps needed for Diabecell to become a cure (by my definition):
First, it needs to work better.  Right now, about 90% of the people who get the treatment, continue to need to use insulin.  That's not a cure for me.  
Second, they need their treatment to last longer.  Since it requires an operation, I think it needs to last at least a couple of years.  Five or ten years (or longer) would be reasonable for a cure for me.

The big unknown for me is how hard will it be to improve Diabecell in these two ways.  If it is just an engineering issue, then that is great news: if they can just tinker with it and gradually improve both the success rate and the duration, that would be great.  They could tinker with it for 5 to 10 years and end up with a cure.  On the other hand, there might be a research issue in there that they need to solve.  That would require scientific research and a breakthrough of some kind to make it more successful and last longer.  Research breakthroughs are much harder to predict.  You might get it in a year, or maybe never.

Getting Approval Elsewhere
Another important question is, how quickly will LCT get approval in other places like the US and the EU?  I'm not an expert in government approval, and I know some of my readers know this area much better than I do.  However, I don't think getting approval in Russia is going to speed up the process for getting approval in the US.  I think they are still two or three large clinical trials away from US approval.  Remember, in the end, only 8 people have completed clinical trials with Diabecell, and that only lasted a year.  Eight or twelve more are in the middle of a second trial.  But even if you stretch this to the max, it is still just 20 people for a year or two each.  I'm not sure if that is enough data to even start a phase-III trial (as defined by the US FDA).

This is an important point: LCT got their approval in Russia, because the standards in Russia are much lower than the US and EU.  (I'm sure the LCT guys will have a much nicer way to phrase this.  And I'm sure they will be unhappy that I'm so blunt.)  But, my understanding is that the research they have done to date is no where near enough to get approval in the US or EU, and they are not trying to, right now.  (As I pointed out above, I'm not even sure it is enough to start a phase-III trial.)  Obviously, if you believe that the US FDA and the EU EMEA over regulate and are a bunch of "nervous Nellies" that tie up promising treatments in red tape, well here is your chance to get a treatment that hasn't yet gone though all that approval process.  To be a little crass: nothing bad happened in the first 20 people; your kid (or yourself) can be number 21.

The LCT press release talks about starting a pivotal study in New Zealand in 2011.  (Pivotal usually means the first phase-III study, designed to provide proof of efficiency and safety. Remember that even after this study, to get US approval they will need to do a second ("confirmatory") phase-III study and get marketing approval.)  So it still feels to me like they are 3-6 years away from approval in either the US or EU.  Although the Russian approval was quicker than I thought it would be, so maybe these guys are just faster than I expected.

Cost and Availability
Dr. Elliot at LCT estimated a cost of AU$ 150,000 per operation to start, which is pretty close to US$ 150,000.  There was no mention of exactly how soon the procedure would be started.  There are issues of training, and of transporting the cells from New Zealand to Russia.  At the start, there will be volume limitations, based on the size of LCT's herd of pigs. With that all said, I assume as more people get the procedure done, there will be economies of scale, and it will get cheaper.  An important part of the economic calculations is how long the implanted cells will work.  After all, $150k once is quite different than $150k every ten years, or every year!  And we don't know how long it will last. 

What's The Big Deal?
One way to look at this news is this: nothing has changed in the research.  The results LCT has today are the same as the results they had yesterday.  The only difference is Russian government approval.  So why is this important news?  I think that part of the answer involves the pace of progress in research vs. the commercial world.  Things happen more quickly in the commercial world.  Economic pressure and competition between companies do that.  This news marks part of the transition for LCT from the world of research to the world of commerce.  Not a complete, black and white conversion from one to the other, but a shifting of importance.  Another part of the answer involves availability.  Up until now, you could only get the treatment as part of a research study.  In the future, anyone with money and desire will be able to get it.  So availability will be controlled by the patients who choose to get the treatment, rather than researchers who choose to provide it. (That's over simplified a little, but you get the idea.)

Newspaper article:
Press release:
Previous blogging on LCT:
Previous status on LCT:

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. 
Email:  To get these blog entries emailed to you join the Google Group:

Monday, December 6, 2010

How to find a clinical Trial

The decision to join a clinical trial is a personal one, which I believe is best made between the person with type-1 diabetes (or parents), and their doctor.  However, I know that some type-1s don't have regular endocrinologists, and also some doctors don't tell their patients about available  trials (for a number of reasons).  Therefore, I've put together this blog on how to find clinical trials, so that people with type-1 diabetes, who want to, can discuss these trials with their medical team.

Non-Honeymooners: Don't think that just because you have established type-1 diabetes, there are no clinical trials worth participating in!  This is not true, on two separate fronts.  First, there are some trials aimed a curing established type-1 diabetes. (LCT, Exsulin, Liraglutide, Xoma 52, are examples.)  Second, there are always lots of trials about better treatments for type-1 diabetics (which I do not cover in this blog) but which can improve the "standard of living" of established type-1 diabetics.

Honeymooners: Many of the studies currently underway that may lead to a cure somewhere down the line, are only recruiting "honeymoon" diabetics.  Usually, people who have had type-1 diabetes for a few weeks or less. (Although this varies study to study.)  So, for trials aimed at curing type-1 diabetes, honeymooners are most in demand.  But the honeymoon time period is also the hardest for type-1 diabetics and their families.  They are getting used to so many new things: blood checks, counting carbs, dosing, needles or pumps or both, etc.  So in that way, it is a bad time to be participating in a clinical trial.  This is a fundamental dichotomy that each family must work out for itself: do you want to participate in a clinical trial soon after diagnosis, or not?

Finally, please don't wait for me to publish a posting calling for volunteers for a specific clinical trial: I don't do that.  I publish when a study starts, but often it is only recruiting at one or two places then.  More recruiting centers often come "on line" in the weeks or months after I post.  So use the web sites described below to see when a trial is recruiting near you.  While I don't push specific clinical trials, I do hope that all type-1 diabetics (both newly diagnosed and long established) consider the available clinical trials.  While the decision to enroll is for each person/family to make themselves, I think it would be a shame not to even consider the possibility.

How To Find Clinical Trials for Type-1 Diabetics

If you are looking for clinical trials, then JDRF already has exactly what you are looking for:
I'm not sure how good the coverage is internationally, but in the US, it seems quite good.

If you can not go to the link above, then go to JDRF's  main page:
and click "Get Involved"
and then "Participate in a Clinical Trial"
and then "Register Now"

It you need to fill out some data, like how old you are, and when you were diagnosed, and some other stuff, and then it matches you up with clinical trials in your area. Pretty sweet!

Although run by the JDRF, it returns clinical trials no matter who is funding them.  You get a list of results, and the trials that are funded by JDRF have a little "JDRF" icon on them.  Once you are registered, it will send you email every now and then telling you about new clinical trials in your area, for your age, and that match your profile.  You configure how often you get these emails.  The emails contain links to simple data pages, that tell you the basics of the clinical trial, where it is being done, the inclusion/exclusion criteria.   All very nicely done.

If you want to do more searching on your own, then you can check out the following web sites:
The Immune Tolerance Network (ITN) is a very interesting organization, which I view as part of the "infrastructure" of diabetes research.  They help researchers organize and run clinical trials aimed at stopping autoimmune attack, and similar subjects within the immune system.  They cover research into type-1 diabetes, and also related autoimmune diseases.  At any one time, they usually have a dozen or so studies going on, and a couple are recruiting all the time. 

Because ITN runs a network of doctors who cooperate in clinical trials, their trials often recruit at many different sites all over the US (and sometimes the world), so you have more chances to enroll.   Their studies are more likely to be available near you.

About ITN:
Type-1 Studies Recruiting Now:
This is the official FDA registration site for clinical trials.  It covers just about everything in the US, and many trials not done in the US are registered here as well.  It contains a lot of information, but is a little clunky to use.  I think it is more designed for research professionals, than random people looking for a trial.  You can search for phrases like "type-1" and "diabetes" and limit your search to studies that are recruiting right now, and even by location where they are recruiting.   Personally, I've found the JDRF site has the same information and is much easier for a patient or parent to use.  But the FDA site has more info, so if you find a trial using the JDRF site, you can look up the same trial on this site, and learn more about it.
This is the UK's official registration site for clinical trials.
This is the UN's official registration site for clinical trials.
You can try this in Australia.

Finally, if you are near a major university or diabetes research center, you might want to "reach out" to them.   I know that UC San Francisco, Stanford, The Barbara Davis center at University of Denver, DRI (in Miami), University of Florida at Gainsville, the Joslin center and Harvard (both in Boston) are all doing multiple studies.

Some of the information in this blog entry comes from a "sticky" Diabetes Daily thread:

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.  I have no relationship with any person or company running any clinical trial or recruiting for any clinical trial.
Email:  To get these blog entries emailed to you join this Google Group:

Wednesday, December 1, 2010

Possible Cures for Type-1 in the News (late Nov)

Here are various news items on possible cures for type-1 diabetes which are in human trials, and related items:

Diamyd Completes Enrollment of their Second Phase-III Trial

Since this study follows people for about 15 months, it is very reasonable to expect that it will complete in mid 2012.  Since this is the second phase-III trial, if successful, market approval might come in 2013 or 2014.  Diamyd is a vaccine like treatment designed to teach the body's own immune system to stop attacking it's own beta cells.  The company's description is this: "Diamyd® is thought to induce tolerance to GAD, thereby intervening in the autoimmune attack and preserving the capacity to produce insulin in patients with autoimmune diabetes".  Remember, the phase-III trials are only in honeymoon diabetics.

Press release:

Leptin Starts a Phase-I Clinical Trial, but as Treatment, not Cure

I have blogged in the past about Leptin:

And here is the press release for the new news:

Back in 2008 Leptin was presented (in the news, at least) as a possible cure, but by April 2010 it was presented as a possible new treatment.  This most recent news makes it clear that it is a possible treatment for type-1 diabetes, not a cure.  I don't expect to cover this research moving forward.  Remember that even as a treatment, it takes 10 years to move through the regulatory process and get approved.

Single case of Putting Type-1 into Remission for One Year
This is a single patient report (not a research study).  The patient had two diseases: ITS and type-1 diabetes.  To treat ITS, she was given Rituximab about 15 months after being diagnosed with type-1.  The result was that her type-1 diabetes went into remission for 11 months.  (No need for external insulin during that time).   This is reported here:

Obviously, this is interesting.  Especially since there has already completed a phase-II study on type-1 diabetics, and got good results there, too.  (Although I'm embarrassed to say that I've not blogged on the specific results of that study.)

Rituximab targets the CD20 part of the immune system's B cells (different from the pancreas's beta cells) to try to prevent the autoimmune attack. B cells are part of the body's immune system and communicate with the T cells, which actually attack the body's  beta cells in the pancreas.  By targeting the B cells, it is hoped this treatment will stop or lower the attack of the "bad" T cells.

Comment: Most treatments aimed at stopping the autoimmune attack are very focused on stopping the "bad" T cells which directly attack the beta cells in the pancreas.  This treatment (if successful) opens up a whole 'nother way to stop the attack: by targeting the immune systems communication and support system, the B cells.

I have previously blogged on Rituximab here:
And reported status here:

Cautionary Note: Possibly Faked Phased Clinical Trial Data
This news article made me very nervous; the impact could be to many other clinical trials. 
Here is the article:

The basic summary is this:  MannKind is developing an inhaled insulin doing several clinical trials in foreign countries, using contract clinical trial companies.  (These are companies that specialize in just doing clinical trials for other companies.  They don't develop drugs.  They do testing of other company's new drugs.)  A MannKind employee claims that some of the data reported by the contract clinical trial company in Russia is obviously false.  All patients had the exact same blood pressure.   Since FDA relies on these studies to do approvals, this is a big deal.  This one case impacts MannKind, but the general problem could effect others treatments as well.  Did that contract clinical trial company do other trials for other drugs?  Is the problem limited to one company, or does Russia have systematic problems that put all Russian clinical trials at risk?  You get the picture: it's bad.

Omission from Previous Blog Entry
In my last blog (comparing Burt's treatment with LCT's) I did not include the fact that LCT's clinical trials were all people with established type-1 diabetes, while Burt's were all honeymooners (people with recent onset type-1 diabetes).  This is a serious omission.  Working on established type-1 diabetes is a huge advantage over honeymoon type-1 diabetics, and that is a strong point in LCT's favor that was not included in the comparison.  I'm sorry for this omission.

General Background Information

All "Animal Models" are not Equal
This is an interesting blog entry about "animal models" used to test type-1 cures:

General Background for Understanding Type-1 Research
This article describes the immune system in general, what is meant by "honeymoon" and other useful words and ideas, but the Teplizumab clinical trial it talks about has since been stopped.  Also the phase-I/phase-II/phase-III description is for new drugs or treatment.  Already approved drugs or treatments can follow a slightly different path.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.