Diabecell Research Closes Out (With Comments on Encapsulation In General)

Diabecell is an encapsulated pig beta cell treatment aimed at curing type-1 diabetes.  This research started in the 1990s, and was part of a group of encapsulated stem cell cures which were developed at the same time by different companies/research groups.  Most of the others ended in the late 1990s and early 2000s, but LCT continued and is still operating today.  I've blogged many times on this research: https://cureresearch4type1diabetes.blogspot.com/search/label/LCT

The last two running studies on Diabecell were marked as "completed" in October 2017.  The most recent clinical trial started in 2011, and published some results in 2016, but they were not strong.  Since it has been two years since their last results, and they have not started a new trial in that time, and also because the results of their trials have been lack-luster for years before that, I'm going to drop them from active coverage here.

Discussion

This should serve as a cautionary tale for all encapsulated beta cell cure research.  There were at least 4 companies trying to cure type-1 diabetes this way in the 1990s, and it looks like all of those were unsuccessful.  There was another crop of these in the 2000s, and most of those have been unsuccessful as well.  (Although Viacyte, founded in 1999 as Novocell, is still in active development and may yet cure type-1 diabetes.)  More recently, in the 2010s there has been another batch of start ups in this area (Dr. Melton's Semma Therapeutics, Beta-O2 Technologies, etc.), and also an even larger batch of new academic research (such as recently reported at Cornell, UCSF, etc.)

I'm positive about all this research. I'm positive about all research aimed at curing type-1 diabetes. I hope it all works. I hope any of it works (because it only takes one cure). However, I do think it is important not to get to overly excited about encapsulated beta cell research (even as it sounds straight forward), because it's obviously more complex than it sounds.

Especially, it is clear to me that the hard part is the encapsulation part, not the beta cell part.  The pig beta cells used by LCT generate the insulin that people with type-1 diabetes injected for decades (from the 1920s to the 1970s).  Those cells work just fine, so LCT's problems are encapsulation.  Other companies have used human beta cells from cadavers.  Those cells worked just fine for their previous owners, which reinforces my belief that the breakthrough that makes encapsulated beta cells successful is going to be on the encapsulation side, not the beta cell sourcing side.

Recent Clinical Trial Records:
https://clinicaltrials.gov/ct2/show/NCT01736228
https://clinicaltrials.gov/ct2/show/NCT01739829
https://clinicaltrials.gov/ct2/show/NCT00940173

Academic encapsulation research in the news:
http://news.cornell.edu/stories/2018/01/removable-implant-may-control-type-1-diabetes
https://www.ucsf.edu/news/2017/10/408731/innovative-type-1-diabetes-approach-licensed-encellin


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

LCT Update

LCT gave a presentation in late 2015 with an update on their "Diabecell" encapsulated cell technology. They have been testing this in people for more than 10 years, and you can see my previous blogging on them here:
http://cureresearch4type1diabetes.blogspot.com/search/label/LCT
The following blog posting covers LCT's history up until about 2008:
http://cureresearch4type1diabetes.blogspot.com/2008/12/lcts-research.html

LCT uses pig beta cells encapsulated in a proprietary coating, so patients do not need a lifetime of anti rejection drugs.

The new information is from eight patients in a phase-II trial who were followed for about 2.5 years. The trial was done in Argentina.  All the patients got two transplants.  The first group got a medium dose, and the second group got twice as much.  The results are still being analyzed, but the basic results seem to be:

• A1c before the transplant was between 8.5 and 9.5, and afterwards was around 7.5 (for the lower dose group) and 6.5 (for the high dose group).
• At the same time, insulin dose dropped about 10% in the lower dose group, and 25% in the higher dose group.
• They presented data on fewer "unaware lows" and estimates of how much insulin the transplanted beta cells were generating.  

Discussion

I think that these are some of the best results I've seen for encapsulated beta cells, but it is still hard for me to get excited about them.  Earlier on, I was hopeful that they could just transplant more cells and get better results, but that does not appear to be happening.  Specifically:

• A phase-I trial reported in 2008 that overall insulin usage dropped 24%, and reported two patients went insulin free, one for weeks and the other for months.
• A phase-II trial reported in 2010 that overall insulin usage dropped 30%, but no reports of people going insulin free.
• A phase-II trial reported in 2013 that overall insulin usage dropped 20%, and no reports of going insulin free.
• A phase-II trial reported in 2015 that overall insulin usage dropped 10% and 25% (in different groups), and no reports of going insulin free.

I find this lack of progress to be disheartening.  It does not feel like they have "cracked the code" to an encapsulated beta cell cure.  At least not so far.

It will be interesting to see how LCT's Diabecell results compare to Viacyte's VC-01 results.  Both companies are working on encapsulated beta cell cures, so a head-to-head comparison makes sense when Viacyte's phase-I (40 person) results come out in 2017.  Hopefully LCT will have results from a similar number of people by then as well.  

Press release and presentation: http://www.asx.com.au/asxpdf/20151116/pdf/433073gv8cc3wx.pdf
This presentation contains a lot of data from several different clinical trials and case studies.
Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT01739829

Joshua Levy 
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Possible Cures for Type-1 in the News (Sept)

This blog posting is a collection of little news items, rather than a single large one.

Two Year Delay for LCT

In a very brief announcement, LCT said that it would delay general commercial availability of it's encapsulated pancreatic product (DIABCELL) from 2016 to 2018.  It sounds to me like they hit a problem in their phase-II study (an open label clinical trial in Argentina), and they need to fix that problem before continuing with their testing for approval.

LCT is developing an encapsulated islet cure for type-1 diabetes. Pig beta cells are wrapped in a coating and implanted into people.  The beta cells generate insulin in response to glucose, while the coating prevents the body's immune system from rejecting or attacking the new beta cells.  Several groups are developing technology like this, but LCT is the farthest along, as they are the only company with results from multiple human trials.

News: http://www.irasia.com/listco/au/lct/press/p130829.htm
Press release: http://www.lctglobal.com/html/blob.php/ASX_130829.pdf?attach=0&documentCode=5126&elementId=20084

ATG (Thymoglobulin) is Unsuccessful in a Phase-II Clinical Trial

ATG (non-human sourced, human T cell antibody infusion) is approved in the US for transplant rejection issues (not type-1 diabetes).  This was a phase-II clinical trial involving 58 people to test it's use for type-1 diabetes.  After one year, the C-peptide production in the treated group and the placebo group was about the same.  Here are two summaries of the results:

Our findings suggest that a brief course of ATG does not result in preservation of β-cell function 12 months later in patients with new-onset type 1 diabetes.

We recorded no between-group difference in the primary endpoint: participants in the ATG group had a mean change in C-peptide area under the curve ...

Press Release: http://www.sciencedaily.com/releases/2013/08/130827203920.htm
Summary: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70065-2/fulltext
Wikipedia information: http://en.wikipedia.org/wiki/Thymoglobulin

Phase-I Results of Dapagliflozin as a Treatment

Dapagliflozin is a pill used for treating type-2 diabetes.  It has been approved for use in the European Union, Japan, and elsewhere, but was rejected by the US FDA.  It has been resubmitted for approval in the US, and that second approval is still under consideration.  It is in a family of drugs called SGLT-2 inhibitors.  

Because the drug has already gone through phase-I, phase-II, and phase-III testing for type-2 diabetics, this early trial in type-1 diabetics was a phase-II study.  62 patients from 5 different locations were included.  Half got the drug, half got a placebo.  All had A1c numbers of 8.5% or higher and were treated for 3 months. 

The results were good, for a treatment.  A1c numbers dropped 0.7 to 1.0 for treated patients, and BG numbers were 30-40 points lower. 

Canagliflozin (Invokana) is a similar SGLT-2 inhibitor which is approved in the US, but I don't think it's been tested on type-1 diabetics as yet.

I don't plan to cover Dapagliflozin in the future, because it is a treatment not a cure, but I did think it was an interesting drug for type-1 diabetics who have trouble controlling their BG and have higher than desired A1c numbers.

Press release: http://www.clinicalendocrinologynews.com/news/top-news/single-article/dapagliflozin-explored-in-type-1-diabetes/5b2de5a29aa324691649e6a01768441b.html
Wiki: http://en.wikipedia.org/wiki/Dapagliflozin

Good Sources of News

I know that it is hard to find good news sources these days.  Two sources that I think are worth reading are:

DiaTribe newsletter: http://www.diatribe.org/ 
This is one of my favorite sources of information.  These guys understand type-1 diabetes and all of it's complexities.  They are not just cutting and pasting other people's press releases into their news articles, but actually applying their own knowledge and expertise to their reporting and analysis.

Ellen Ullman's Scoop.it page: http://www.scoop.it/t/diabetes-and-more   
This is a collection of media news stories, but it is a very good collection of media news stories. Unfortunately, the media does not do a good job of reporting on type-1 cures or treatments.  The reasons for this are too complex to discuss here.  But Ellen's page is my favorite way of reading about diabetes in the media.

Note that both of these sources cover both type-1 and type-2 diabetes, so be ready to mentally filter out the type-2 stories, if you only care about type-1.

Donating to Non-Animal Research

I was asked the following question: "I like to donate every year to help find a cure [for type-1 diabetes]. However, I don't want to support testing on animals. Have you come across any research groups that you think are effective but don't test on animals?"

I don't know of any research aimed at curing type-1 diabetes that has never used animal trials. Indeed, it is hard to see how such research could exist, given our current technology, and the technology we expect to have for the foreseeable future.  Curing type-1 diabetes is expected to require both changing the immune system and regrowing beta cells.  Both of these are complex interactions that occur only within actual animals.  There is no way to test either one of these effects in single cell organisms (which don't have separate immune systems or beta cells), or tissue samples, or in computer simulations.  So researchers either need to test on animals, or guess wildly, and then test in humans.  The second path is blocked by the FDA (because it's unsafe), but even if not, it's almost impossible that such guess work could lead to a cure.  

Now, if you want to only donate to research which is not currently using animals (which has already transitioned into human trials) then there are several research projects to choose from.  Any research in human trials would be a good target.  You can see a list from last September here:
http://cureresearch4type1diabetes.blogspot.com/2012/09/jdrf-funding-for-cure-2012.html
and I expect to post an updated list for this year in a few weeks.

But to put it bluntly: right now, if you are not willing to fund animal research, you are not going to fund a cure for type-1 diabetes.  For type-1 diabetes, cell cultures, tissue samples, and computer simulations are not good enough for research use.

Joshua Levy -- http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Possible Cures for Type-1 in the News (January)

I feel like I'm about two month behind, but this will get me closer to current news.

Kamada Reports Early Results from A Phase-I Trial

News: http://www.globes.co.il/serveen/globes/docview.asp?did=1000799026&fid=1725
Press Release: http://www.kamada.com/press_item.php?ID=29
Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01304537

I struggled quite a while with their press release, but in the end, this is my summary:

Kamada releases results from their phase-I trial, which they describe as "positive". However the data in the press release is too vague for me to come to any conclusion about weather their drug worked. I'm looking forward to a complete, peer reviewed paper.

Kamada manufactures Alpha-1 Antitrypsin (AAT).   You can read more about it here:

http://cureresearch4type1diabetes.blogspot.com/p/drugs-and-treatments-in-clinical-trials.html

and my previous blogging here:

http://cureresearch4type1diabetes.blogspot.com/search/label/AAT

AAT is an anti-inflammatory chemical which the body makes naturally, and which is already FDA approved for people who have a rare condition where a person doesn't make enough of it on their own.

These are the first results from the first phase-I clinical trial completed.  Unfortunately, there was no control group for this trial, so there is no way to compare people who got AAT with people who did not. The company's press release said that "almost all patients reached glycemic control below 7.5%" and that "the majority of the patients maintained levels of C peptide higher than ... 0.2 pmol/mL".

None of that is bad news, but this trial was for honeymooners (within 6 months of diagnosis).  So none of those results sound particularly stellar to me.  This is where a control group would be particularly helpful, because we could have seen a difference between the two groups, if there was one.  Because people with type-1 diabetes naturally vary a lot during their honeymoon, it is at this time that control groups are most important.  

I've asked the company when the full results will be published, and those might be much more interesting.  At the very least we should be able to see how the C-peptide numbers change over the  study.  That can be compared to the "normal" drop during the honeymoon phase.  My general feeling is that if this data is all the data they publish, then the trial was a failure.  They need to publish more data, especially C-peptide changes to show success.

Discussion

This study is important for a couple of reasons.  First, because of the number of AAT clinical trials. I know of a five AAT clinical trials aimed at type-1 diabetes going on now.  That's a lot; more than any other single drug.  So having mediocre results from the first study completed is not welcome news for any of the others.  Second, because of it's impact on the inflammation theory of type-1 diabetes.  This theory holds that inflammation destroys the beta cells in the pancreas.  The autoimmune reaction triggers inflammation, but does not directly destroy the beta cells.  This theory has never been the majority viewpoint (most researchers think that inflammation is a side effect of the destruction of beta cells, rather than a cause) but it is an active minority opinion.  Since AAT is an anti-inflammation drug, it is one of the first drugs to test this theory.  Since AAT does not appear to have a strong effect, that suggests that the whole inflammation theory might be wrong as well.  That would be unfortunate, since stopping inflammation is a lot easier than stopping the auto-immune attack!  Because there are lots of anti-inflammatories out there, there would have been lots of potential drugs to prevent type-1, if this theory panned out.

It is interesting to me, that even though this study did not have a placebo group (an untreated group), they did have three different levels of treatment.  Some people got 40mg of AAT, some people 60mg, and some people 80mg.  The press release did not include any difference in results between these groups.  That's a little ominous for me.  For a drug that is effective, I would expect one dose to be the most effective; others less so.  On the other hand, if the drug has no effect, then all the groups would be the same, and in this case, no differences were reported.

LCT Updates

Background: LCT is developing an encapsulated pig beta cell cure for type-1 diabetes.
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).

When last we left LCT, they were finishing a small phase-II trial in New Zealand, and starting a small phase-II trial in Argentina.  Links to press releases for the results and the follow on trial are below:
http://www.lctglobal.com/html/blob.php/121122%20LCT%20-%20Strong%20interim%20results%20in%20Argentinian%20%20DIABECELL%20trial.pdf?attach=0&documentCode=4774&elementId=20084
http://www.lctglobal.com/html/blob.php/121122%20LCT%20starts%20DIABECELL%20Phase%20IIb%20trial%20in%20Argentina.pdf?attach=0&documentCode=4775&elementId=20084

The Argentinian Trial

All the patients got two rounds of implanted islet cells, 12 weeks apart.  Half the patients got a base level, and the other half got twice this level.  The patients who got more islets had better results, which were:

• average insulin dose reduced by 20%
• a reduction of HbA1c from a pre-transplant average of 8.6% to an average of 6.7% at 12 weeks following the second implant
• up to 70% reduction in unaware hypoglycaemic events.

Obviously, this isn't a cure in it's current form (but see below for follow on products).  This study involved a total of 8 people, and so an obvious thing to do is to expand it, and the expansion was also announced.  LCT will implant an additional 20 people, all at the higher dose level.  For me the most interesting information in their press release is this:

“We are using an ‘adaptive trial design’ for our pivotal studies and so the data generated in this 20 patient trial will likely form the foundation data for our registration package,” said Dr Andrea Grant, Chief Executive, LCT. “We remain on track to meet our goal of completing clinical trials of DIABECELL by 2015 and having a product commercially available by 2016.”

I'm not an expert in this area, but I would be surprised if they could register a new medical implant for use in the US based on data from one study of 20 people (and their previous studies which contain about 24 people all together).  Especially with no clinical trials actually done in the US.  I assume that commercial availability will be in one or more of the countries where they have done research: New Zealand, Argentina, etc.

If you want even more information, you can read their CEO presentation, also done in November 2012, here:
http://www.lctglobal.com/html/blob.php/LCT%20AGM%20CEO%20Presentation%20Nov%202012.pdf?attach=0&documentCode=4762&elementId=20084

Which includes a slide "DIABECELL -- The path to patients" which lists four studies:
      A New Zealand phase II study [8 people]
      An Argentinian phase-II study [8 people]
      An Argentinian phase-II/III study [20 people, discussed above]
      A New Zealand and/or German Phase-III study [unknown size, not discussed above]
That forth study would make more sense to me, although I'm still not sure that this would get them approved in the US.  For comparison, the recent anti-CD3 drug approval attempts used two 300 person studies, one of which was done in the US.  And the pivotal DiaPep277 studies on-going right now are the same: two studies of 300 people each.  Maybe implants require less, but that much less?

No News from Russia

I'm also a little mystified because LCT had previously announced that their product had already been approved for sale in Russia:
http://cureresearch4type1diabetes.blogspot.com/2010/12/lct-gets-commercial-approval-in-russia.html
However, since then I can not find any reference to anyone selling it in Russia, or LCT getting any revenues from such sales. (But I don't speak Russian so can't search effectively in that language. If there are any Russian speakers out there, who would like to do some searches, please look for "LCT Biomedical Limited" (the company name) and/or "Natalia Dolgova" (the first company director) and tell me if they are selling anything in Russia.  If you find the web pages, I can Google Translate them.  But so far, I haven't even found them.)

LCT General Update

It is very rare for any executive at a medical company to make predictions about the future.  There are all kinds of rules about what they can and can not say.  So I was quite surprised (and happy!) to see these public posts from "elliott" in a posting on www.islet.org.  Dr. Bob Elliott is a founder of LCT.

Multi-centre Phase 3 studies will comemnce Q1 2013 and be completes by Q1 2015.
Registration based on a successful outcome will take anything up to a year, so we anticipate the LCT product will be marketed by Q1 2016 ie three years from now.
It will not cure diabetes, but is likely to be a valuable way of treating unstable diabetes.
'Fast follower' products will start to be tested clinically in 2014.

'Fast Follower' refers to the next generation of products. We are always seeking ways to improve the product but each improvement as seen in preclinicla studies in animals has to be tested in humans.   I have not give up on the idea of complete insulin independence, and we are making steady progress.

'Unstable' diabetes is the indication we are working on in the trials. But of course all Type 1 diabetics have unstable blood glucose control to a greater or lesser degree, so it really becomes a matter of how bad things are. 

He also said that they have improved the product since the peer-reviewed results were published in 2007, with the implication that they expect better results in the future then they reported in 2007.

Note that his statement that "Registration ... will take anything up to a year" might be true in some countries, but my belief is that in the US, marketing approval (our version of commercial registration) takes 1 to 2 years, especially if measured from the end of a phase-III trial.  I would not be surprised if other countries where LCT operates have faster registration processes.

Finally, I want to say that although LCT describes this 20 person Argentinian trial as "Pivotal" and "Phase-III", I will continue to refer to it as phase-II because of it's size. To be honest, I've seen phase-I trials with more than 20 people enrolled, so I think calling it a phase-II is proper.  Now if LCT gets approval in the US based on a 20 person trial, then I might change my standards. :-)

LCT's web page is http://www.lctglobal.com

Rituxan Safety in Rheumatoid Arthritis

Rituxan (also known as Rituximab or MabThera) is a monoclonal antibody which is being tested as a possible cure, or part of a cure, for type-1 diabetes.  My previous blogging is here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Rituximab
Monoclonal antibodies are a relatively new technology for developing drugs (only about 20 years old), but already about half of new drug approvals are monoclonal antibodies.  However, some people have expressed worries that, as a class, monoclonal antibodies are unsafe, or their safety profile is unknown or suspect.

This study is a big step towards putting those fears to rest. Since Rituximab is already approved for rheumatoid arthritis, these researchers followed people who used it for that purpose for many years.  The basic result was that people on the drug had a lower disease rate than similar people not on the drug:

The rate of serious infectious events for the 1,145 patients on Rituximab for more than 5 years was 2.76 per 100-person-years, and the rate for the 818 placebo patients in the studies was 3.6 per 100-patient years, they said.

"No new safety signals were observed with increasing duration of exposure including in patients with more than 5 years of follow-up."

"the rates of myocardial infarction [type of heart attack] (0.40 per 100 patient-years) and malignancies were consistent with those observed in epidemiological data from other RA cohorts (0.48 to 0.59 per 100-patient years for MI)."

News: http://www.medpagetoday.com/MeetingCoverage/ACR/35895

Note that many monoclonal antibodies have names that end in mab.  So if you see a drug named Joshuamab or Curecommoncoldmab or anything ending with mab, it is likely to be a monoclonal antibody.

Rituxan as an Injectable Drug

Currently, Rituxan must be given intravenously, rather than being injected under the skin, like insulin.  The difference is important, because intravenous administration usually requires a "medical setting" (like a hospital or clinic, or at least trained medical staff).  While we all know that under skin injections are commonly done everywhere and by anyone, with a little training.

Recently Roche announced publication of two studies showing that they had a formulation of Rituxan which could be injected and was "not inferior" to the intravenous formulation already approved.  Since "not inferior" is the FDA's requirement for approval in situations like this, that's good news.  Even better news is that the basic technology that they used to convert a previously intravenous formulation into an injectable formulation can be applied to other drugs as well.  So with luck, they will be able to make lots of drugs easier to administer.

Press release: http://www.roche.com/med-cor-2012-12-08b.htm

Update from Scott King on Islet Sheet Project

An Islet Sheet is a specific beta cell encapsulation technique, similar to what LCT is trying to do.  Because Islet Sheets have not yet started human trials, I don't follow this research very closely.  However, I know others are very interested in it, and Scott King posted an update on his blog, which you can read here:
http://www.hanumanmedicalfoundation.org/blog/2012/11/26/signal-breakthrough-islet-sheets-thrive-in-pig/

They are hoping for more animal trials in 2013.  King is a very insightful guy and previous blog postings are interesting as well.

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. My blog contains a more complete non-conflict of interest statement. 
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

Possible Cures for Type-1 in the News (June)

LCT Starts A Phase-II Trial in Argentina

LCT is developing an encapsulated pig islet cell product.  The hope is by implanting these cells, people with type-1 diabetes will not need to measure their BG level or inject insulin, and the cells will keep their BG levels in normal range without an external help.

LCT has gotten government permission to start a phase-II trial in Argentina.  They expect to dose 8 people in the second half of 2011.  Each person will get to implants about 3 months apart.  LCT has already run a phase-I trial in Russia, and a phase-II trial in New Zealand.  But together, those trials have treated only 20 people.  This trial will bring the number up to 28.  Previous results were that one patient was did not need external insulin for a few months, and another was insulin free for a few weeks.  Several other patients used less insulin after the implantation, for weeks or months.  From my point of view, that's a long way from a cure, but LCT has been working to improve their encapsulation technology and their islet cell processing technology, and research is always about doing better in the future.

http://www.lctglobal.com/html/blob.php/974605%20(2).pdf?attach=0&documentCode=3453&elementId=20084


Are Pharma Companies Paying Your Doctor?

The guys over at Pro Publica have gotten a hold of several databases of doctors who are being paid by pharmaceutical companies, for various reasons.  The companies provided this information to the government, but Pro Publica has also taken it and made an easy to search database.  See if your doctor is getting paid for speaking, or for meals, or for any other reason.  (Look up names like "Smith" and "Jones" to get a feel for how much money is involved.)  I never thought a lunch or two really mattered, but some of these guys are getting more than $35,000 in one year, and that's enough to make you wonder.  Or at least make me wonder.

http://projects.propublica.org/docdollars/

Xcell (Adult Stem Cell Clinic) Shut Down in Germany

Every few months, I get asked about for-profit clinics that offer to cure various aliments (including type-1 diabetes) by injecting people with their own adult stem cells.  I'm working on a detailed posting about these clinics, but in the meantime, there is one less clinic to worry about:  Xcell, with two locations in Germany, has been shut down.

I definitely got more questions about Xcell then about similar clinics in Mexico, Argentina, Thailand, the Ukraine  China or anywhere else.  I think being located in Europe gave them an aura of respectability missing from other clinics.   Years ago, they announced that they were going to start a clinical trial on type-1 diabetes.  I searched diligently, but never found any evidence that the actually had started the study, and certainly no results.  But they always had great on-line testimonials from people with type-1 diabetes (and many other illnesses) who they had "helped".

News coverage:
http://www.bionews.org.uk/page_95103.asp
http://www.telegraph.co.uk/news/worldnews/europe/germany/8500233/Europes-largest-stem-cell-clinic-shut-down-after-death-of-baby.html

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.
Blog: http://cureresearch4type1diabetes.blogspot.com
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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!
http://www.last.fm/music/Blur/+videos/+1-OSB3SUh3Xd8

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.

Discussion

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: http://news.smh.com.au/breaking-news-national/animaltohuman-transplant-first-20101210-18sfk.html
Press release: http://www.lctglobal.com/html/blob.php/LCT%27s%20Diabecell%20Registered%20for%20Sale%20and%20Use%20in%20Russica_101210.pdf?attach=0&documentCode=2409&elementId=20084
Forum: http://islet.org/forum/messages/54131.htm
Previous blogging on LCT: http://cureresearch4type1diabetes.blogspot.com/search/label/LCT
Previous status on LCT: http://joshualevy.pbworks.com/w/page/13864073/DiabetesCureReadyForHumanTrials#DiabecellbyLivingCellTechnologies

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. 
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials
Email:  To get these blog entries emailed to you join the Google Group:  http://groups.google.com/group/type-1-diabetes-clinical-trials-news

Snarski Confirms Burt's Phase-I Results

First, a little background.   The "Burt" clinical trial in Brazil is one of the very few clinical trials which has actually cured people of type-1 diabetes.  I know that is a provocative statement, so let me be clear:  Some of the people treated in this trial did not need to use external insulin (yet still had reasonable A1C numbers while eating normal diets) for a long as the study ran.   Some of these people were followed for years.  This was not just a "couple of week" or even a "couple of months" event.  

But, there are important safety issues to consider with this treatment.  Basically, the treatment is to "reboot" the immune system, hobbling the immune system, and then treating it so that when it comes back, it does not attack the body's own beta cells.  There are two serious safety issues here: first, during the time the immune system is down, the patient must stay in an isolation ward in a hospital, and is subject to opportunistic infections.  Second, the act of shutting down the immune system is a big deal, and might cause problems "down the road".  Cancerous tumors are a particular worry.  Neither of these risks is completely unknown.   Very similar immune system "reboots" are used today to treat cancer, and some other autoimmune diseases and their safety is understood.  Never the less, the general level of safety is lower than other possible cures for type-1 diabetes.

So, with all that as prelude:
 

Snarski Confirms Burt's Phase-I Results
Second trial cures type-1 diabetes, in people, for months, but at what risk?

A Polish team has run a clinical trial very similar to Burt's, and gotten very similar results.  Since Burt's results are the best in terms of curing type-1 diabetes, this is good news indeed! 

The results from the published paper is pretty simple: 8 patients were treated, and 7 of them did not need external insulin again, for as long as they were followed.  They were followed for an average of 7 months (longest was 16 months).  The one who still required external insulin used about 10% of the dose before treatment.  In personal communication this group said that as of November 2010 they had treated 15 patients and that 11 of them had remained off insulin (median remission duration of 16 months).

This team used a protocol very similar to Burt's, although not identical.  However, the entire discussion of safety that applies to Burt applies here as well.

Some Discussion and Opinions

Because of the safety issues, I was interested in how many people volunteered for the treatment.  For this group, 19 patients were offered enrollment, and 8 accepted it.  So that means that basically 40% of the people who had the chance, considered this treatment "safe enough" to try it.  This was an adults only trial, so the people making the decision are making it for themselves (not for their children). I would assume that as this treatment becomes more common, the perceived safety would go up.

The researchers for this trial consider the chance of death from this treatment to be less than 1 in 100 (but are are not specific about how much below it is).


Encapsulated Beta Cells vs. Immune System Reboot: Head to Head Comparison

In terms of results in people, there are two approaches to type-1 diabetes which are head and shoulders above the others: Encapsulated Beta Cells (with LCT in the lead), and Immune System Reboot (Burt and Snarski).  No one else has cured type-1 diabetics for any length of time.  So here is a (slightly irreverent) head to head comparison:

Cure Rates

Encapsulated Beta Cells: less than 20% of the people go into remission for over two weeks.
Immune System Reboot:  more than 80% of the people go into remission for over two weeks.

For patients that did not go into remission, they generally used less insulin (for both treatments).  However, I think the drop was great for the reboot patients, but I don't have detailed data to support that.

Cure Duration
Encapsulated Beta Cells: averages less than 3 months.
Immune System Reboot: averages over 10 months.
Note: these are both very rough estimates!

Cure Safety

Encapsulated Beta Cells: Very safe: no known short term or long term side effects.  Out patient surgery.
Immune System Reboot: Less than 1% chance of death (but how much less?)  Also, very  small additional risk of cancers years or decades after the treatment.  Surgery and hospitalized recovery time, lasting many days.  No serious side effects seen so far.

Experience with the Cure

Encapsulated Beta Cells:  Less than 16 people, Max duration less than 2 years.
Immune System Reboot:  Over 30 people, max duration over 4 years (maybe 6 years in Brazil, I need to get updated information on that trial).
(This includes some personal communication from the Snarski group.)

Snarski Abstract: http://www.nature.com/bmt/journal/vaop/ncurrent/full/bmt2010147a.html
Burt Abstract: http://www.ncbi.nlm.nih.gov/pubmed/19366777
Another Abstract: http://www.ncbi.nlm.nih.gov/pubmed/19773265

Dr. E Snarski was kind enough to send me a pre-print of his group's paper, and provide valuable information for this blog posting.  Of course, all mistakes here are my own.  One comment that Dr. Snarski made very specifically was that "we should not yet talk about cure - rather the word remission should be used".  I used the word "cure" in some parts of this posting, but that's me.

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. 
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

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

Below are some updates on research into curing type-1 diabetes.   Remember that I generally only cover clinical trials: research done in people.


AAT (Alpha-1 antitrypsin) Starts A Phase-I Trial

I've blogged about AAT in the past, here: http://cureresearch4type1diabetes.blogspot.com/search/label/AAT
The good news is that they (finally!) actually started their phase-I trial:
http://www.marketwatch.com/story/omni-bio-announces-first-infusion-in-phase-iii-clinical-trial-of-alpha-1-antitrypsin-in-recently-diagnosed-diabetic-patients-2010-10-18?reflink=MW_news_stmp
The announced that they were going to start the trial back in June, but this is the actual start of dosing for the first patient.


This is an anti-inflammatory drug, which the body makes naturally, and which is already FDA approved for people who have a rare condition where a person don't make enough of it on their own.  You can read my general comments about all inflammation based cures: http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation

Here is the clinical trial for "part 1" of the trial:
http://www.clinicaltrials.gov/ct2/show/NCT01183468
And here is the record for "part 2" of the trial:
http://www.clinicaltrials.gov/ct2/show/NCT01183455


Part 1 is 16 people and part 2 is 66.  Both are honeymooner's only (within 100 days of dx).  Together, they are supposed to run from Oct 2010 to Nov 2014, but I'm very hopeful that they will publish their part 1 results sooner than that.  They need to do part 1, before they start part 2.  However, the treatment phase will last at least 2 months, and then each patient will be followed for 2 years, so this is not going to be a quick result.  Part 1 is currently only recruiting in Emory University, Atlanta, Georgia, USA.   Contact: Stephanie Meisner     404-785-8136     type1diabetes@emory.edu.  However, they hope to recruit in many other places soon, including Barbara Davis Center; University of Colorado, Aurora, Colorado, USA, and (the only California location) University of California San Diego, La Jolla, California, USA.  Based on Dr. Lewis's comments (see below) they might already be recruiting at Barbara Davis Center.

Because AAT is already approved for use in people, it could start out at as a phase-II trial or even a phase-IV trial.  Both parts of this trial are labeled "phase-II" but since AAT has never been used on type-1 diabetics before, and part 1 only has 16 people, I prefer to think of part 1 as a phase-I clinical trial, and part 2 as phase-II.

In addition to all that, thanks to a anonymous but alert reader over at CWD, I can include a link to the following web with discussion by Dr. Lewis, who is deeply involved in AAT research:

http://www.healthcentral.com/diabetes/c/248704/108450/inflammatory-2
Be sure to read both page 1 and page 2, and most especially Dr. Lewis's answers to the many comments.  Also remember that he is covering both type-1 and type-2 in different parts of his text and helping transplants (rather than directly curing type-1) in some parts, so you need to understand the context of the question to understand his answer.
He is really positive about this.  Of course, everyone should be positive about their own research.  :-)

I would be particularly careful about his answer to question 9.  Especially during the honeymoon phase, you might get that kind of result from luck.  It's important to remember that's just one personal testimonial.  It is the kind of thing that motivates a clinical trial, but not a replacement for a clinical trial.  Finally, if anyone who does medical research professionally has any thoughts on his answer to question 13, I'd be interested in your opinions; especially the "AAT activity" part.


LCT Update


Basic summary is that they have now dosed 10 out of the planned 12 person clinical trial in New Zealand. (LCT refers to this a phase-II trial, and it is their second one, but it's also much smaller than other phase-II studies: 12 people, instead of the 50+ people that is common.)  The longest follow up was for one year.  The first 4 people got 10ku/kg and have been followed for 30 or more weeks, the second group of 4  got 15ku/kg and have been followed for 8 or more weeks, and the last group of 4 got 20ku/kg and are still being dosed.  


The first group's average insulin needs dropped by about 30%, but no one was reported to have gone "off insulin" for any length of time.  Both first and second groups had a large drop in low blood glucose episodes.

Press release: http://www.lctglobal.com/html/blob.php/LCT%20NZ%20Trial%20Update_271010.pdf?attach=0&documentCode=2264&elementId=20084 

Some Discussion and Opinions
This news definitely feels like more of the same.  Normally, more of the same (repeating your results) is a good thing.  And it may be a good thing here, also.  However I'm a little nervous that the dosage has gone up a lot: 5ku/kg to now 15ku/kg, but the results have not gotten better.  (At least that I can see from their published data.) Part of that is that the early 5ku/kg guys, some of them got extra transplants.  But still, whatever is happening, it does not look like simple giving more islets is going to result in big improvements.  At least not in a straight forward (linear) way.

The last group from this last clinical trial got the highest dose so far: 20ku/kg, and their data has not been reported on at all.  I hope that they do better than the earliest 5ku/kg group.  (Meaning at least 25% go insulin free for some period of time, for example.) 

El-Khatib Artificial Pancreas Update

Here is an "feel-good" article about the artificial pancreas being developed at Boston University
http://articles.latimes.com/2010/nov/01/health/la-he-diabetes-pancreas-20101101
This is an artificial pancreas which is unique in that it can dose insulin if the person goes high, and glucagon, if the person goes low.  Obviously, this gives it some interesting advantages over an AP that can only dose insulin.


This is the paragraph which summarizes where they are right now:

So far, Damiano's team has tested its algorithm in 15 people in one- to two-day experiments. The first trial, in which they tested adults for 27-hour stretches, demonstrated that safe and effective glucose control was feasible with the two-hormone artificial pancreas. In the second trial, currently underway, they are testing the system in children and adults for 51 hours and have included an exercise component. (Since exercise can lead to increased risk of hypoglycemia, this adds an additional level of challenge to the algorithm's decision-making process.) Because the trial is ongoing, the team is hesitant to draw early conclusions, but Damiano says that they are very encouraged by the results.

And where they hope to be in the future:

Damiano says he hopes to be performing out-patient trials by 2012 and estimates that the device could be on the market by 2015.

There was one wrinkle to this research, which I had not known before:

One of the hitches, however, is that glucagon is not yet approved by the Food and Drug Administration for long-term use because it breaks down in solution. Several companies are tackling that problem. In the meantime, since a system that uses only insulin is likely to be FDA-approved sooner, Damiano's team is working on an insulin-only system as well.

Some Discussion and Opinions

The "out patient" trials they refer to in 2012, mean wearing the AP outside of the hospital.  Right now, all testing is done in a hospital.  Also, I think the 2015 date for FDA approval is a little optimistic.  From a regulatory point of view, they would need to do phase-II trials, phase-III trials, and get marketing approval, all within five years. (And that's separate from the scientific work of developing an AP that worked, and the engineering work of figuring out how to produce it!  Nor is it counting separate approval for long term glucagon,)


Personal Notes
I want to thank everyone over at BB for their huge outpouring of support.  You guys have no idea how many emails I got; it felt wonderfully supportive. 

I feel that my blog looks a little "old", so I'm going to update how it looks sometime this month.  So don't be surprised if it suddenly changes it's look, and then changes again to something else!  If anyone has ideas on improvements to how the blog looks, or the static text on the blog page, now would be a great time to email me or leave a comment.

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. 
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

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

 
GCSF (Neulasta/Pegfilgrastim) Starts a Phase-I Clinical Trial
This is straight forward trial where GCSF is given to people in the honeymoon phase of type-1 diabetes.  It is interesting for many of the same reasons that the ATG+GCSF trial is interesting (see older post on ATG+GCSF).  Both of these trials are being done at the University of Florida, and Dr. Michael J. Haller is involved in both.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00662519

There is a second GCSF clinical trial being done at the University of Padova (Padova, Padua, Italy), but it is not aimed directly a curing type-1 diabetes.  Although I don't understand it fully, it appears to be more basic research into GCSF effects on people with type-1 diabetes.  Clinical trial record is here: http://www.clinicaltrials.gov/ct2/show/NCT01102699

A Little Discussion: Why a GCSF only Trial?
One obvious question that came to mind when I saw this GCSF only clinical trial, done at the same place and time, and by the same researcher as doing the ATG and GCSF trial, was: why do both?  I mean, if GCSF works, then certainly ATG and GCSF will work, and clinical trials are a lot of work and expense.

The answer to this question (for me) has to do with with three separate, but related goals:

1. We want to cure type-1 diabetes. (Cure Product Development.)
2. We want to learn how drugs effect type-1 diabetes, so we can find a cure.  (Basic research.)
3. We want the FDA to approve clinical trials which lead to points 1 and 2.

If you only look at point 1, then a GCSF-only trial (when a GCSF+ATG trial is also ongoing) might sound like a waste of time.  As a parent of a child with type-1 diabetes, I often focus only on point 1.  However, product development flows out of basic research, so points 2 and 3 are also important.  It may turn out that studying GCSF alone will help create a cure in the future, or that the FDA might require more knowledge of GCSF alone before it will approve some future clinical trial, which leads to finding a cure.

In the past I have blogged about not understanding how  Sitagliptin alone, or Sitagliptin and Lansoprozole combined, could cure type-1 diabetes.  However, it may be that these clinical trials will be valuable, because of points 2 or 3 above.  They might be the basic research or FDA required background that eventually leads to a cure, even if they are not the cure themselves.

LCT Announces Completion/Extension of their Phase-II Trial
LCT has announced these things in August:

1. Their phase-II trial has been extended with 4 new patients who will get dose 20k u/kg dose.  The phase-II study now includes 4 who got 10k u/kg, 4 who got 15k u/kg and these 4.  This is a 50% expansion of their study, at 33% higher dose.
2. The first four patients have seen a benefit of fewer (or elimination) of low BG episodes.  Only two such events, compared to nineteen, so almost a 90% drop.
3. They plan "commercial launch" in 2013, and "global reach though partnership".  They seem to be assuming that the operation will cost about $150k (I think this is US$, but not sure.)
4. They have also laid out the following time line for getting to commercial availability, which is the most detailed that I've seen:

• 2011: Continue phase-II trials, get approval for phase-III trial (They use the term "pivotal".)
• 2012: Complete phase-III, report on results.
• 2013: "Approval and revenue"

That's their plan, and I hope they make it.  I see the following issues for them to overcome.  First, they need to have a cure.  Right now, the longest they have had anyone insulin-free is 32 weeks, and only two people (out of twelve) have been insulin free for any number of weeks.    Obviously they need to improve both of these numbers.  (Although, if you view them as a treatment to help brittle diabetics, then their results might be good enough already - depending on how long they last - but that wouldn't be a cure.) Second, they need to treat enough people to get their approvals.  Right now, they have treated a total of 16, with 4 more on the way.  That is far fewer patients than any other phase-II trial that I know of.  A more common count is 20-30 in the phase-I trial, 80-120 in phase-II, and 300 in a phase-III "pivotal" trial, and then a second phase-III trial for confirmation.  (Basically all the drugs in phase-III trials have followed that path.)  LCT is running at about 1/3 the size in their phase-I trial, and 1/10 the size in their phase-II.


Press release: http://www.blogger.com/post-edit.g?blogID=5472921328078253036&postID=548554300707664816
Corporate Overview: http://www.lct.com.au/downloads/cms_latest_news/2010-08-26-Presentation%20August%2010.pdf
This corporate presentation contains a lot of information on where they are, what they plan to do in the future, and how they plan to make money.  It is targeted at investors, after all.


NovImmune has started a phase-II for NI-0401
This company is very hard for me to follow, because they don't issue many press releases, don't have the clinical trial records, that most other researchers have, and it is just generally hard to find information on them.  The  are a small, relatively new company and their lead product (the one farthest along is the drug development process) is NI-0401 which is and anti-CD3 drug, generally similar to the Teplizumab and Otelixizumab. 

Their recent corporate literature makes it clear that NI-0401 has started a phase-II clinical trial for type-1 diabetes.  Unfortunately, I have not been able to find clinical trial records for either the phase-I or phase-II trials, so I have no ideas how many patients are involved, if they are honeymoon or not, or any other of the most basic information about the study.  Even worse, I can not find any published results for the phase-I study in type-1 diabetics.  (I did find results for their phase-I trial on Crohn's disease, but not tyoe-1.)


Corp presentation: http://www.swissequitybiotechday.ch/media/biotechday/downloads/novimmune.pdf


AP News: Faster Insulin
Below is a link to a JDRF press release on their project to created faster acting insulin (mostly to help their Artificial Pancreas project):
http://www.eurekalert.org/pub_releases/2010-08/jdrf-jlr081610.php
I normally would not cover it, because it doesn't talk much about results or progress, however I did want to mention it because it is much broader and contains more context than your usual press release.

Most press releases just cover one piece of news for one line of research, but this press release gives a lot more useful context to the search for faster acting insulin.  Basically, it starts out with a goal.  The goal is to get faster acting insulin, mostly because it will make creating an artificial pancreas easier, and make the resulting pancreas better.  (Obviously,  it will also help everyone who uses insulin with meals, which is basically all type-1s.)  The simplest way to speed up insulin (and the way done in the past) is to create a new form of insuilin which is faster than the currently available forms.  And JDRF is funding Dr. Buckingham at Stanford to test one of those.  Another way is to find a faster pathway into the body.  So JDRF is funding Dr. Zisser testing of AFREZZA, which is inhaled insulin; the hope is that inhaled equals faster.  A third idea is to use microneedles to deliver insulin faster (JDRF is working with BD on this one).  A fourth is a port-system which puts insulin from a standard pump directly into a person's liver.  Since insulin mostly effects the liver, this could speed up the effectiveness of pumped insulin.  (JDRF is working with Roche on this.)  Finally, there is a post-pump insulin warmer which might also speed up insulin effectiveness.  (JDRF is funding Dr. Tamborlane of Yale to test this for InsuPatch.)

My Opinions.....
The whole point of research is that you don't know which projects are going to pan out and which are not.  This press release shows how JDRF is trying many different possible paths to faster insulin.  Some of those paths seem like good ideas to me.  Others seem very inventive, if a little strange.  Others don't strike me as unlikely to succeed.  I'm sure other people looking at the same list will expect different research to fail and succeed than I do.  That is why JDRF is funding all of them.  No one knows which will pan out.  I believe that this whole project is part of JDRF's "glucose control" research area, and that whole section includes about 6% of their funding.  So even though it sounds like a lot of different research projects in different areas (and it is!), all together it is only a few percentages of JDRF's total investment.   It doesn't even begin to touch the 33%+ aimed at immune therapies or the 40% aimed a regrowing beta cells.

JDRF Page on Spending: http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&page_id=0B36CA86-9128-4C49-B7D8F55955507931




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. 
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

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

Low Dose Naltrexone starts a Phase-I Trial

Background
Naltrexone was approved in 1984 for use in treating heroin addiction, but was never widely used, because of strong side effects.  The low dosage level is one tenth the dose approved, so it is much lower, and doesn't have these strong side effects. Low Dose Naltrexone (LDN) is undergoing several clinical studies aimed at different diseases.

Here is how the researchers describe this trial:

The purpose of this early study is to see if a drug called naltrexone should be studied more in people with Type I diabetes and hypoglycemia unawareness. This study will show whether naltrexone could reduce hypoglycemia unawareness. The study will also show, by using magnetic resonance imaging (also called MRI), whether naltrexone changes the way blood flows in the brain when a person is experiencing hypoglycemia.

Discussion
I'm not sure if I'm going to follow this trial as a potential cure, because it seems to be focused very specifically on "hypoglycemia unawareness", and that is not a cure.  On the other hand I mention it here, because I know that some people are very interested in Low Dose Naltrexone, and it is the first time LDN has been tried on type-1 diabetes.  Unfortunately, they are going going to be measuring blood flow in the brain, and too-low blood sugar events.  Some people think that LDN might result in lower insulin requirements, and producing more natural insulin.  However, this trial is unlikely to detect that (unless they test for more things than are mentioned in their clinical trial record). 


Clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT01053078
Wikipedia: http://en.wikipedia.org/wiki/Naltrexone 
Facebook group: http://www.facebook.com/group.php?v=info&gid=342192490776 


LCT's DIABCELL: Two Year Delay to General Availability

Dr. Elliot (a major player at LCT) said in a public forum:

"We do not anticipate being in the clinic before 2013 and even then in a very limited way."   Source: http://islet.org/forum/messages/53927.htm

This is a two year delay compared to their previous statement (in a yearly report) saying that they hoped to be doing transplants in Russia by 2011.

Also, LCT made a very nice presentation at ADA, which you can see here:
http://www.asx.com.au/asxpdf/20100628/pdf/31r13z624mnx7g.pdf
The really interesting slides start on page 30 and runs to the end (although slides 22 and 27 aren't bad, either).

Artificial Pancreas Photo
Here is a link to a "puff piece" in a Boston newspaper about the "bihormonal" (glucagon and insulin) AP work:
http://www.bu.edu/today/node/11148
The reason I include it is because it starts out with a big photo of a person with this AP.  Notice the five different "sets" on the person's abdomen.  It's a good reminder of where AP is and is not. How far we have come with an AP, and have far we have yet to go.

Dr. Ward's Artificial Pancreas Trials
This newspaper article describes some AP trials being done in Oregon, USA:
http://www.earthtimes.org/articles/press/an-artificial-pancreas-closer,1359773.html

These guys are testing a bihormonal (glucagon and insulin) AP device, similar to El-Khatib's group in Boston, Massachusetts, USA.  However these guys are using a different computer algorithm to control the hardware.  The key achievements include an average BG of 138 and "nighttime hypoglycemia was reduced nearly to zero".  Testing was for a 24 hour period.  I think that 21 people were involved.  (The newspaper article says "21 experiments".)

Stem Cells
I recently came across a group of 8 stem cells experiments (mostly phase-I) which did not require long term immunosupressives.  So those could be part of a future cure.  For example, if Diamyd, DiaPep, or any of the anti-CD3 treatments currently in phase-III trials pan out in honeymoon diabetics, then these stem cells might extend that cure to people with established type-1 diabetes.  I will devote a future posting to these Stem Cells trials.  With the 3 stem cell trials that I already knew about, that's 11 total. 


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.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

Possible Cures for Type-1 in the News (April)

LCT Will Start Phase-II Clinical Trials in New Zealand
LCT Publishes results from Phase-I Clinical Trials in Russia
Background: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#DiabecellbyLivingCellTechnologies
Blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/LCT

Two pieces of good news from LCT, who are trying to cure type-1 diabetes by implanting encapsulated pig beta cells.  First, they have got permission from New Zealand to start a phase-II clinical trial.  Second, they published 18 month follow up results from the eight patients they treated as part of their phase-I trial in Russia.

Phase-II Permissions
Basically, they are half way done with their New Zealand phase-I study, but they can now call the second half the start of a phase-II study.  There is a clear progression here.  The first guys in Russia got about 5ku/kg, while the second half got 10ku/kg.  The first half of the New Zealand patients also got 10ku/kg, but the second half (the phase-II part) are getting 15ku/kg.  Right now, they have 8 patients as part of the Russian phase-I and 4 more as part of the New Zealand phase-I.  The second half of the New Zealand trial (the phase-II part) is 4 patients.  I don't think that is even close to enough people to finish a phase-II.  (80 or more people is normal for a phase-II.)  But it does get them started. And milestones are all about getting things started.

Congratulations to LCT for moving from phase-I to phase-II clinical trials!

Phase-I Results
I'm sorry that I don't have time to discuss their results, but I don't think they are radically different from the previously released data.

Press release: http://www.news-medical.net/news/20100330/LCT-receives-approval-for-New-Zealand-Phase-II-human-trial-of-DIABECELL.aspx
Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT00940173


Atorvastatin (Lipitor) completes enrollment of Phase-II Trial

Background: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#AtorvastatinbyWilli

Blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/Atorvastatin

Dr. Willi at Children's Hospital of Philadelphia is running an experiment where he gives Atorvastatin (Lipitor) to newly diagnosed type-1 diabetics.   I would summarize the rational behind this trial as "it worked in mice, and the drug is already approved, so let's try it".  This is the more official version from the study:

Preliminary studies have shown that members of the statin family of medications, including atorvastatin (Lipitor®), preserve beta cell function in a mouse model of type 1 diabetes. These finding suggest that use of atorvastatin in combination with insulin therapy may delay and potentially reverse the destruction of beta cells in patients who have recently developed type 1 diabetes. Atorvastatin (Lipitor®) is approved for use in adults and children (>10 years of age) who have elevated blood cholesterol levels. This study will examine whether atorvastatin (Lipitor®) may also help the body preserve insulin production in patients with newly diagnosed (within 8 weeks) type 1 diabetes.

In Feb 2010, this study finished enrolling patients.  This is important, because it is now possible to predict when they will finish collecting data.  (This study runs for a year, so they should have data collected by Feb 2011.)

More on GAD and Diamyd
I'm not big on posting links to other sites.  I figure if you want information from the net, you will go find it.  And since you know exactly what you want, and I don't, you will do a better job find links that you want to read, than I will.  However, I thought the link below was a particularly good overview of the history of Diaymd's drug (currently in phase-III trials - honeymoon only - and in the lead for eventual FDA approval):

http://www.diabeteshealth.com/read/2010/03/23/6611/the-story-of-gad/

My Web Page is Finally Updated
In addition to this blog, I have a web page where I try to keep status information on each treatment currently in clinical (human) trials.  However, this web page had gradually become out of date.  However, I have recently put a lot of time into updating it:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

One of my major goals for this update is so that when I blog about a particular piece of research, I don't need to include basic information on that treatment.  Instead, I just have a link back to the web page, which describes how each treatment is expected to work.  You can see that philosophy in action, below.  Although I've made many improvements to the web page, it still has a ways to go.  Several of the descriptions of specific trials need more information and organization.


News on Animal Trials
Remember always: even successful animal trials usually don't result in human trials.  And even if they do, it is over 10 years from start of human trials to market approval, and none of the treatments discussed below have even started human trials, yet.

Leptin
Leptin is a hormone which has treated type-1 diabetes in NOD mice, and I've blogged on it before.  But the last time, I thought that an injection of leptin cured type-1 mice.  However, that was not true.  (My mistake.)  Instead, the mice were given a gene which caused them to generate their own leptin from that point onward, and they did not need insulin after that.   So the goal of this research is to use Leptin as a treatment for type-1 diabetes.  For mice it replaced insulin, but for people it might replace insulin or a combination of leptin and insulin might be a better treatment that insulin alone.  But in any case, leptin is being tested as a treatment for type-1 diabetes, not a cure.


I think the biggest news now is this paragraph:

Unger's team first asked permission to start human trials almost a year ago, he said. The hospital is prepared, they have an ample supply of potential volunteers, and they've lined up funding. What's holding the process up, Unger said, is getting the manufacturers of leptin to set up the logistics to guarantee the supply.

Usually, people are complaining about lack of money, not lack of drug.  So I think it is very likely that a clinical trial will start soon.  I know of one other Leptin study that has been running for years, (at Columbia) so maybe Dr. Unger's team can ask the Columbia team about their supplier. :-)


Newspaper: http://www.dallasnews.com/sharedcontent/dws/news/healthscience/stories/030210dnmetdiabetesstudy.1668e2147.html

I'm not sure that I will cover this moving forward.  It is interesting and unique and new, but I don't think it is a cure.

CureDM
These guys are working on a protein which stimulates the growth of beta cells (so much like Exsulin).  They cut a big deal with Sanofi-Aventis.  They will get millions of dollars, based on making development milestones, and (if successful) Sanofi-Aventis will market their new drug and pay royalties.   They hope to start human trials later this year.  The headline for this news article, which I think sums up the situation perfectly is this:  Sanofi-Aventis Places Large Bet on Diabetes Drug Candidate.

News article: http://www.medicalnewstoday.com/articles/185008.php
Press release: http://www.curedm.com/news/2010.04.08_curedm_press_release.pdf 

I do not think that simply growing more beta cells will -- by itself -- cure type-1 diabetes, because the broken immune system will attack the new beta cells same as the old.  But I do think it could be part of a cure: http://joshualevy.pbworks.com/ConceptsAndBackground#RegrowingBetaCells

New Cure in Mice (by Dr. Pere Santamaria)
Vaccine-like cure works in mice.  Remember: mice cures seem to be found about 4 times a year (over 145 so far), and so far none of these has led to a cure.  So this is good news, but not break-through news.

News article: http://www.businessweek.com/lifestyle/content/healthday/637852.html

I usually include a link to the abstract, and here it is:
http://www.cell.com/immunity/retrieve/pii/S1074761310001226
but it was so technical and dense that I had trouble understanding it, although it was written in English. 

Joshua Levy

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