Monday, July 14, 2014

ADA 2014: Type-1 Diabetes Cure Research, Immunology

This posting discusses two treatments which have the potential to cure type-1 diabetes, which have been tested on people, and which were reported on at the ADA's 2014 Scientific Sessions.  They were both tested in honeymoon diabetics (as I define "honeymoon").

The soundtrack for this posting (in honor of the Ramones,  RIP):
http://grooveshark.com/#!/s/What+A+Wonderful+World/1XjvmQ?src=5

Expanded Polyclonal Tregs

There was a presentation of results from a clinical trial on Expanded Polyclonal Tregs, which I've blogged about before:
http://cureresearch4type1diabetes.blogspot.com/search/label/Polyclonal%20Tregs
Remember that this line of research is being pursued by two teams: the UCSF team (led by Dr. Gitelman) which is reported on here, and a team at Medical University of GdaƄsk lead by Dr. Trzonkowski.

A quick summary of this treatment is as follows: remove one specific type of T regulator cell (called "CD4(+)CD25(+)CD127(lo)") from a person with type-1 diabetes.   Grow them out so you have about 500 times more, and then put them back in the body.  Since regulatory T cells naturally regulate the body's immune system, the hope is that they will prevent the autoimmune attack which causes type-1 diabetes.

The UCSF team ran a phase-I clinical trial with 14 people.  There was no placebo group and the patients had type-1 for between 3 and 24 months.  The basic results were that after two years, these patients continued to generate C-peptide at the same rate as when they started the trial.  There was no drop off in C-peptide production.  That means there was no drop off in insulin production.  Since all these people were already diagnosed with type-1 diabetes, they were not generating much insulin, however people with type-1 generally generate less and less insulin over time.  So these patients did better than would be expected of an untreated group.   (Although as a pilot study, there was not an untreated group here.)

Source: ADA 2014 Presentation 174-OR.

ATG and GCSF

There was presentation of results from a clinical trial on Antithymocyte Globulin (also called Thymoglobulin or ATG) and Granulocyte Colony Stimulating Factor (GCSF).  I've blogged on this trial before:
http://cureresearch4type1diabetes.blogspot.com/2012/08/possible-cures-for-type-1-in-news-early.html

The basic idea behind this research is that ATG modulates the body's immune system, while GCSG causes the body to generate more T-cells directly from it's own bone marrow.  So this therapy is a combo therapy with one treatment to stop the autoimmune attack, and another to restore beta cells.

This study had 17 patients who got the treatment, and a placebo group of 8 who did not.  People had type-1 diabetes for 4-24 months when they received the treatment.  Basically, the 8 untreated people lost C-peptide production (which means they lost insulin production), just as you would expect.  The 17 treated patients ended up, after one year, at about the same C-peptide level from where they started. So they did significantly better than the untreated group.

This news article covers this research as well:
http://www.gainesville.com/article/20140619/ARTICLES/140619588
But note that this story has some phrases like this "there was an increase in the insulin-producing beta cells in the pancreas" which is overselling, in my opinion.  This treatment preserved beta cell levels; I don't see evidence that it increased them.

The most interesting quote in this story is the following forward-looking view from the researcher:
[Dr.] Haller said the eventual goal, years down the road, is developing a therapy that first uses an IV infusion of Thymoglobulin and then a Neulasta [trade name of GCSF] treatment once every two weeks for three months to greatly reduce or eliminate the need for some Type 1 diabetes patients to take insulin injections.
Another interesting point, is that both ATG and GCSF are already FDA approved for other uses.  This makes them easier to use in clinical trials, and means they could be used "off label" for type-1 diabetes, if prescribed by a physician.

Source ADA 2014 Presentation 173-OR.

Discussion

First, these two studies highlight the lack of standardization in terminology used to describe "honeymoon" type-1 diabetes.  The first study enrolled people 3-24 months after diagnosis, and used the term "recent onset" (which I interpret as a more scientific way of saying "honeymoon").  The second study enrolled people 4-24 months after diagnosis, and used the term "established" (which I interpret to mean "non-honeymoon").

For my part, I'm considering both of these clinical trials to be "honeymoon" tests, because they included people who had been diagnosed for less than a year.  That's the dividing line I've used informally in the past, and I'm going to continue to use it, until I see a better definition.

Second, I view both of these results as honeymoon style results.  If they gave these treatments to people with long established type-1 diabetes, one would expect no improvement because the group would start out with no C-peptide production. On the other hand, these treatments have real benefits to recently diagnosed type-1s (who still have some insulin production), and could be even more beneficial to people who are losing insulin production, but have not yet been diagnosed. This is the hallmark of a honeymoon style result to me: it is highly dependant on how long a person has had type-1 diabetes.

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, JDCA, or Tidepool 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.

Sunday, July 6, 2014

ADA 2014: Type-1 Diabetes Cure Research, Artificial Pancreas


At the 2014 ADA Scientific Sessions, there were several reports on progress on artificial pancreas (sometimes called "closed loop").  Unfortunately, all of them were reported on a day that I was not at the convention, so the information below is mostly from the printed materials at the convention, news reports, and convention "buzz".

The "Bionic" Pancreas:
Bihormonal, Closed Loop, Artificial Pancreas Progress


This was clearly the big news of the scientific meeting.  Here is my previous coverage on this (and it includes links to DiaTribe's more complete coverage):

Bihormal refers to supplying both insulin and glucagon (so it can raise or lower a person's blood glucose).  Closed loop artificial pancreas refers to automatic dosing as needed with data from a CGM to a pump without human intervention.  Bionic is a marketing name used by Dr. Damiano's group at Boston University.

There were two big publications on the Bionic AP.  The first was in a scientific journal, published the month before the show, and the second was a presentation at the show.

First, I'l discuss the study published just before the show.  The basic set up was that people wore the devices for one day of calibration, and then two days of data collection.   Data was collected for four groups: adults and adolescents, and people who signaled when they were going to eat a meal, and those that didn't.  No one counted carbs or dosed in response to meals.  The signaling group just told the AP that they were about to eat a breakfast, lunch or dinner; nothing about the content.

Group
  Average BG  
  Estimated A1c  
  % in range  
(70-180)
Adults Before Treatment7.3
Adults who signaled meals1326.280
Adults without meal signaling1426.770
Adolescents Before Treatment7.9
Adolescents who signaled meals1627.368
Adolescents without meal signaling1757.760

What this means, is that for adults who did not signal when they were going to eat, they had an average BG level of 142, a likely A1c level of 6.7 (if they had done this for 3 months), and their BG levels were in range 70% of the time!  Now, that looks pretty good, but the news gets better.

Here are the results from the follow up study, done by the same researchers, and given as a scientific talk.  This study was "free range" adults who were free to roam over 3 square miles of Boston, staying in a hotel, working out at a gym, and eating mostly at restaurants, while the adolescents were attending camp.  For this study, no one signaled meals.  It included 20 adults and 32 adolescents, which makes it phase-II sized by my reckoning.

This study has only two data points that matter:

Average BG Number
  (for both adults and adolescents)  
  Estimated A1c  
138
6.4

There was slight complexity in the data.  That 138 number was the average over all five days of the test.  The researchers expected that the first day would be worse than the other four, because the unit was calibrating itself to the patient the most during that first day.  For adults, this worked out, the next four days average BG was 133 suggesting that long term use would result in an even lower number, and might even drop a few more points (over time, as the AP better learned how the person reacted to insulin, glucagon, and food).  But for adolescents, that's not what happened.  They averaged 147 over days 2-5.  Even if 147 (A1c of 6.7) is the long term number, that is still a complete success.   It is lower than the ADA standard of 7.5 for adolescents.  But it is a mystery to me why those days should average higher than the first day.

Summary of NEJM data: http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1314474&iid=t02

Note: information for this section came from an ADA abstract, a JCEM paper, and a NEJM abstract.   You can read the whole NEJM article here:
http://www.nejm.org/doi/full/10.1056/NEJMoa1314474#t=articleTop
JCEM abstract here:
http://www.ncbi.nlm.nih.gov/pubmed/24483160

Single Hormone vs Bihormonal Artificial Pancreas
A group from Canada gave a talk where they directly compared injected insulin, an insulin AP, and an insulin and glucagon AP.  For average BG numbers, they found that both types of APs were similar to each other (the dual pumps were only very slightly better), and that they were both significantly better than injections.  However, when they looked at low BG events, then the dual hormone APs had significantly fewer such events than single hormone APs.  This makes sense, since the dual hormone pumps can directly prevent lows by dosing glucagon.

So this Canadian trial suggests that a bihormonal AP might do a little better than a "classic" AP, but it should not do vastly better, if measured by average BG.  When I first saw that poster, I was a little dubious.  Two hormones seemed like much better technology than one.  But then I saw the results below.  One of the complexities, is how does one measure an AP?  Using average BG is easy and straightforward, but should we also measure low BG events and/or high BG events?  If you do (especially low BG events), then the dual hormone APs might look better in comparison.

The Cambridge Artificial Pancreas

With all the excitement about the bihormonal AP, it is important to remember that there are also several "classic" AP projects out there.  For example, the results from the Cambridge AP, a "classic" insulin-only AP, were almost as good as the bihormonal results.  There were something like 7 presentations on various aspects of this project, so it was very well represented.

The "24 hours a day" trial included 17 people, and ran for 16 days (8 days with AP and 8 days with regular treatment).  They also reported on a nighttime only trial, which ran for 90 days!  Again, half with AP and half with regular treatment.

It's big results that matter, from the 24 hour and day trial, are:

Average BG Number
  (for both adults and adolescents)  
  Estimated A1c  
146
6.7


MD-Logic Artificial Pancreas Project

What's better than two closed loop, artificial pancreas projects?  Three!  The MD-Logic project uses a "fuzzy logic theory algorithm" to predict insulin dosing.  The research group presented a poster, which showed that using the MD-Logic AP at night, improved BG numbers the next day.  This clinical trial included 24 people and lasted for 3 months (6 weeks using the AP, 6 weeks not, for comparison).

People who used the AP woke up about 15 points lower (on average) than people who did not use it. Looking at all the BG numbers the next day, people who used the AP the night before had an improvement of about 11 points on average.  People who did not use the AP were in range about 66% of the time, while those not using the AP were in range about 62% of the time.  (Range was 70-180).

Source is poster 949-P.

The Virginia Artificial Pancreas

This is another ongoing research project into a "classic" artificial pancreas.  In the trial reported on at ADA 2014, 13 people were tested for 42 hours: 14 hours "open loop" treatment, and 28 hours of "closed loop" treatment.  People in the trial could move about a hotel.  This same research group is planning a 2 month trial of the same AP.

Source is poster 954-P and 104-LB.

Direct Comparison

Group
Average BG
Estimated A1c
Size
Adolescents?
Duration
AP Use
Boston University138
6.4
53
Yes5 days24 Hours/Day
Cambridge
146
6.7
17
No
8 days24 Hours/Day
MD-Logic
24
Yes
90 days
Night Only
Virginia
135?
13
No
2 days
24 Hours/Day

When you look at that, you might say the two hormones are better than one.  But I would not read too much into that difference.  It's not huge (8 BG points and 0.3 A1c), and remember that the single hormone solution is simpler all the way around: only one hormone to buy and load into the pump, less moving parts on the device, and so on.  (Not to mention the fact that Glucagon hasn't yet been approved for this application, although that is expected.)  Of course, the comparison is based on average BG, so might miss extra low BG events in the single hormone APs.

None of this competition bothers me in the least.  I love the idea of having four closed loop systems getting to market at about the same time with slightly different feature sets.  Having a bihormonal AP with slightly better control competing against a single hormone AP which is slightly simpler, sounds like just the sort of competitive situation that feeds progress in a capitalist economy.

Other Bits and Pieces

Poster 75-LB compared CGM data from actual BG data (measured using laboratory grade equipment) from blood pulled directly from a vein. They found that CGM data was very similar to the actual BG data, and that even when different, the differences were small. The researchers conclude that existing CGM technology is not the "weakest link" of AP technology.

Poster 747-P asked people who were testing a closed loop AP, what they thought of it. They liked it. They liked it because it provided better BG control, reassured them that nothing bad would happen while they slept, and improved BG control the next day.  Poster 110-LB contained similar information, but focused on the remote monitoring of an AP in a family situation (ie. parents remotely monitoring children).  A major conclusion of this research was that families wanted the AP/remote monitoring combo being tested; it did not need any improvements at all, it just needed to be made available.

Poster 948-P tested a closed loop system using diluted insulin compared to regular insulin, for small children (aged 4-7).  They found that diluted insulin worked a little better.  Average BG levels were the same, but time spent in range was 8% higher when diluted insulin was used.

Poster 951-P tested a closed loop system which (in addition to BG data) also used energy expenditure and galvanic skin response data.  These are two measures of energy use.  The hope was that by using energy expenditure data, they could make a better AP.  However, the data showed very little difference between using this data and not, and even this little difference was only when BG was above 250.

Summary

My summary of closed loop, artificial pancreas research is this:  We are seeing cure level control in phase-II clinical trials and for several different AP systems.  This is great news, for several reasons. First, it means they "only" need to get through phase-III trials (and marketing approval) for these APs to be sold in the US. They don't need to do better than the results they already have, just produce the same results in larger trials. Second, it means that if one falls apart, there are others which can still get marketed. Third, it means that the technology is ready. When one AP is successful, that team might just be ahead of the rest, but if four groups can do it, that means the technology is here for all.

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, JDCA, or Tidepool 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.

Saturday, July 5, 2014

More About ADA 2014

The JDCA recently published a "Flash Report"  based on try trip to ADA 2014.  You can read it here:

It covers some of the same topics that I already posted here, but has some different information in it as well.

Also, as part of attending ADA 2014, I have on line copies of almost all the abstracts presented there, and many of the posters, and a few of the presentations.  So, I'm going to experiment with "doing requests".  If you have a topic (a few keywords, or a sentence) and you would like to know if it was discussed at ADA 2014.  Send it to me, and (If I have time) I will summarize the ADA material that pertains to your topic.  Please note that I don't expect to start this for about a month, so send in now, but expect results in 4-8 weeks.  (Not very internet, I know!)  If you're interested in a specific researcher, I can tell you if they published anything at this meeting.

Joshua Levy

Sunday, June 29, 2014

ADA 2014: Non Scientific Summary

This is my non-scientific summary of the American Diabetes Association Scientific Sessions 2014.  I'm also putting together two or more postings to cover the scientific content, which I hope to publish over the next few weeks.  I want to specifically thank:
  • The Juvenile Diabetes Cure Alliance (JDCA) who paid for my ticket to the conference.
  • My employer (a large software company) which gave me paid time off to cover the convention for JDCA, as part of their "service learning" project, which pays for engineers to spend time working for non-profits.  It is a wonderful fringe benefit. 
As you read this, please remember that the meeting ran from Friday to noon on Tuesday, but I was only able to attend on Saturday, Monday, and Tuesday.

Size vs. Applicability

The first thing that hit me, as I was planning my attendance, was how huge it was.  Especially over the weekend, there were often more than eight sessions going on at the same time.  So the initial worry was "where do I spend my time" and "what do I see".  Unfortunately, when I started looking at the session titles and the exact papers, I realized very quickly that, since 90% of the people with diabetes have type-2 diabetes, therefore 90% of the sessions dealt with type-2 diabetes.  Sometimes there would be one session that covered type-1, sometimes none at all.  Suddenly I was looking at each paper, trying to find something that applied to type-1s.  Then things got worse: most of the papers were about treatments and complications.  So while there were a small number of type-1 papers, only a couple of these discussed cures in any way.  

So my planning ended on a profoundly depressing note.  I was at a huge scientific meeting with over a thousand posters, scores of oral presentations, over a dozen symposia, and very little to see!

I also got particularly unlucky, because the three sessions which covered T1C  (Type-1 Cure) most directly were on Sunday, which I could not attend.  (I'll blog more about these in a future blog, but they covered Expanded Polyclonal Tregs, an ATG/GCSF treatment, and the closed loop artificial pancreas.)

One good thing about the scientific sessions, is how broad they are.  While there were only a few cure focused papers, there were a vast number of papers in general, and they covered far more different subjects that I expected.  I often see people asking "has anyone ever studied teenage depression and type-1 diabetes? or seeing a doctor every 6 months rather than every 3 months? or using this insulin rather than that insulin? or taking insulin N minutes after starting the meal or M minutes before? or ....   One thing I realized while attending ADA is that just about everything related to diabetes has been studied at one point or other.

Science Divided from Commerce

The show has a severe case of schizophrenia, which I hadn't realized before.  There are the scientific tracks, which are all about research for the future (but nothing available now), and the exhibition (the trade show) which was all about what is being sold now (but nothing about the future). And there is a very strong division between the two.

I'm used to software shows.  If you walk around the trade show part of a software show, everyone is excited to tell you about their future products.  At the slightest provocation, they gush about the new better stuff that will be available soon.  But the pharmaceutical industry is highly regulated, and apparently they are not allowed to talk about future products (at least not to non-medical professionals).  I would ask the most innocuous questions "what features will be in your next pump/CGM combo product?" or "[pointing at a huge sign for a type-2 drug] aren't you guys testing that on type-1 diabetics?" and their eyes would get big and they would walk me over to a tiny corner of their booth (often called "medical information") where a specialist would deal with me.

The specialist would ask me two questions "Are you a medical professional?" and "Please sign this non-disclosure agreement (NDA)".   Of course, I'm not a medical professional, and I'm not going to sign an NDA because then I could not blog about what I learned.  So they smile nicely and are very polite, but cannot tell me anything.  So frustrating!  It's a little eerie, also.  It's clear that there is some FDA rule about not talking about future products to non-medical professionals; all the reps, in all the different booths, all say the exact same thing when you ask about research or future products.  It's like they are all sharing one hive mind.

At software shows, it's very common to hear some new research talk, and then wander over to a company's booth and discuss how that paper might apply to their product. But it is not done at medical conventions! I heard a really cool research talk on the advantages of U-500 insulin for type-2s (as compared to standard insulin, U-100). I asked a guy in a pump booth about using U-500 in his pump. His eyes got big, and his expression became a mix of awe, fear, and horror: "U-500 is not approved in our pump!", "you cannot do that! [and I can't even discuss it!]".

The biggest single goal of the exhibition was to get type-2s to take more drugs. Not on insulin? Get on insulin! Taking metaformin? Take something else, too (we've got lots of drugs to choose from). Partly this is because type-2 is a large market, but also it is because there is big room for growth. Type-1s already take insulin, and there is not much more for them to take. But type-2s often don't take insulin, so there is room for sales growth. Plus there are several different classes of adjunct drugs, and they generally don't interact with each other, so if you're taking 1 or 2, there's probably another 1 or 2 you could be taking. More revenue growth.

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, JDCA, or Tidepool 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.

Friday, May 30, 2014

Research In The News (May)

This post is a collection of interesting items that have not yet made it into clinical trials, or which were unsuccessful in previous clinical trials, but are still being worked on.  These are not aimed at a cure.

Comparing Three Continuous Glucose Monitors

This is the summary of a study aimed at comparing CGMs:
The Navigator and G4 Platinum had the best overall accuracy, with an aggregate mean absolute relative difference (MARD) of all paired points of 12.3 ± 12.1% and 10.8 ± 9.9%, respectively. Both had lower MARDs of all paired points than Enlite (17.9 ± 15.8%). Very large errors (MARD > 50%) were less common with the G4 (0.5%) than with the Enlite (4.3%) while the number of very large errors with the Navigator (1.4%) was intermediate between the G4 and Enlite.
Full Study: http://dst.sagepub.com/content/early/2014/04/21/1932296814532203.full.pdf+html%20


New Treatment Option for Type-1s?

LX4211 is an experimental drug designed to cause people to pee out more sugar than normal.  It is designed to cause people to need less insulin at meals, because they can get rid of more sugar by urinating it out.

Quote from the news:
Lexicon said the drug, codenamed LX4211, reduced the total dose of insulin taken by patients at meal times by 32 percent, compared with a 6 percent reduction in patients given a placebo.
News: http://www.reuters.com/article/2014/04/14/us-lexicon-pharm-diabetesdrug-idUSBREA3D0KB20140414

Discussion
When I first heard of this I thought it was a "cheap trick" and not particularly important.  But using 32% less insulin at mealtimes (which is probably about 16% less in total), is a pretty big effect, so it is at least interesting.  I would be even more interested if it improved A1c or BG numbers, since those are directly correlated with better health.  Also, the people in the study had "poorly controlled" type-1 diabetes, but the exact level of control was not stated in the clinical trial record. So it is important to see what happens with people whose control is normal or average.

This drug has been (or is being) tested in a total of 12 clinical trials; one of which is on type-1 diabetics specifically.  The type-1 test was on 36 people.  The study says that people in it must be "willing to refrain from using carbohydrate counting to adjust insulin during the study".  I'm not sure what is going on with that, but if they require people to change their insulin dosing regime as part of the study (and especially to not count carbs), that is certainly something where details matter.

There is a diagram describing how this drug works on the company's web page (but the rest of the page is mostly about type-2):
http://www.lexgen.com/pipeline/lx4211.html


Enzyme Based Artificial Pancreas

This is another way of making an artificial pancreas that uses chemistry rather than electronics. Unfortunately, it looks to me like they are many years away from even starting human tests, and once those start, they are still many more years away from availability.  Still, it is a good idea, and the more different paths to a cure that are being worked on, the better.

News: http://phys.org/news/2014-04-mechanobiology-enzyme-micropump-autonomously-insulin.html

Bi or Tri Hormonal Artificial Pancreas
The link below is to a company trying to develop a tubeless bi or even tri hormonal artificial pancreas.  Sounds interesting, but I can't tell when the website was last updated.  One of the items is a job listing, and it contains the following two quotes:
The CoreMD and "wedges" electronic hardware designs have already been completed. You will work closely with hardware and software engineering senior management in fine-tuning and prototyping (SLA) its pumping mechanism design, making re-design suggestions to save power/space, and capturing that design in SoliWorks. You will then test the SLA and re-design it if needed.  [Which sounds pretty good.]
We are looking for volunteers willing to work "pro bono" (free of charge) [Which does not sound good at all.]
http://pancreum.com/index.html

Serova

Below is an update on Serova's Cell Pouch.  It looks like they had good results on the very early testing, and expect to spend the rest of 2014 getting more, similar data.  They are still testing with immunosuppressive drugs, and obviously, this gets a lot more interesting when they stop using those.

http://online.wsj.com/article/PR-CO-20140422-903834.html

New Delivery Mechanism

The link below reports on another "cured in mice" experiment. This was done by combining GAD-65 IL-10, and an anti-CD3.  (I'm not holding my breath on that getting into human trials; not with the problems GAD65 and anti-CD3s have already had.)  However, I was interested in the dosing method.  They modified (possibly via genetic engineering) a safe bacteria, which is commonly found in the gut, to generate two of the drugs they gave.  This sounds like a very interesting and broadly useful technique, if they can control the dosing sufficiently.

http://diabetes.diabetesjournals.org/content/early/2014/03/25/db13-1236.abstract?papetoc

INGAP Continues

INGAP is a beta cell growth hormone.  It was tested on type-1 diabetics and did not have positive results.  The news article below, which reports on a high school science project, reminds me of two things:

First, some researchers never give up.  Some of them are so committed to their discoveries, that they will continue to work on them even after there have been significant failures in clinical trials. This probably is a good thing; we want researchers who are "all in" and willing to push things as far as they can possibly go, even in the face of failure.  Those are the kind of researchers who will get the eventual cure into our hands.  However, it is important to remember just how committed they can be, when evaluating what they say.

Second, it is always shocking to me just how far technology has gone, in terms of letting younger people do more serious research.  Lab equipment has gotten easy enough to use, and cheap enough to use, so that high school students can do more serious research than they ever could before, and that has to be a good thing.

http://www.montrealgazette.com/news/Montreal+teen+awarded+diabetes+research/9757443/story.html

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, JDCA, or Tidepool 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.

Saturday, May 17, 2014

Secukinumab and Ustekinumab each start Phase-II Trials


Secukinumab and Ustekinumab have a lot in common, including both starting phase-II trials in the last few months, so I'm covering them together.  Both of these drugs are monoclonal antibodies, meaning they are specifically targeted at one kind of immune cell.  (Approximately 1/3 of all new drugs in the US are monoclonal antibodies, so this is not unusual.)  In both cases the drugs have already done phase-I trials for other diseases, so the phase-II trials described here are the first times these drugs have been tested on type-1 diabetes.

Soundtrack for this blog posting: http://grooveshark.com/#!/s/The+Chain/1Ty1wz

Secukinumab

This drug has been submitted to the FDA for approval for treating moderate-to-severe plaque psoriasis (an autoimmune disease), but has not yet been approved.  It has also been tested for some other autoimmune diseases.   Secukinumab is thought to work by blocking inflammation, specifically blocking IL-17, an immune molecule.  Secukinumab was known as AIN457 during development.

The trial has started recruiting, and is expected to run until April 2019, enrolling 100 people.  Half will get the drug, half will be in a placebo group (randomized, double blind).  The primary end points are safety and C-peptide generation after a meal.  Secondary end points include A1c, insulin usage, etc.  This study is funded by Novartis Pharmaceuticals.  They are recruiting people at least 15+ locations all over the US.  Unfortunately, none of them are in the San Francisco bay area.

Ustekinumab (Stelara)

This drug was approved in the US in 2009 for treating psoriasis, which is an autoimmune disease (where the immune system self attacks skin cells rather than pancreas cells, as with type-1).  It has also been tested on multiple sclerosis, Crohn's disease, and sarcoidosis (also all autoimmune diseases).  Ustekinumab is thought to work by blocking inflammation, and specifically blocking two immune molecules called IL-12 and IL-23.

This trial will run from July 2014 to March 2016, and will enroll 20 people, in 4 groups of 5 people. There is no control group; each group will get a different dose of the drug.  The primary end points are all safety related, the secondary endpoints are all immunology related, but there are "exploratory" endpoints which are the results a person with type-1 would care about: C-peptide measurements, insulin usage, and A1c.  The study is being done at the University of British Columbia, by a professor in their dermatology department.  I assume he has experience with the drug's use on psoriasis. It is funded by JDRF.


Discussion 

These studies brought up two points for me:

First: They show the power of money and capitalism in getting research done.  The JDRF (a non profit) is funding the Ustekinumab study, and they can only afford to dose 20 people (no placebo group).  On the other hand, the Secukinumab study is funded by industry, and they are dosing 50 people and in addition have a full placebo group.  It is nice to have money.

Second; conspiracy theorists will need to ignore the Secukinumab study, because it doesn't fit with their "corporate America is making too much money to cure type-1" theory.  That study is being funded by Novartis Pharmaceuticals, which makes a huge amount of money off diabetics.  It is a classic "Big Pharma" company, yet here it is funding a drug that might be a cure for type-1.  Why?  Because they think they can make more money faster by curing type-1, than by treating it.  And they are afraid that if they don't, someone else will, and they'll be left with nothing.  The other company will get all the money from the cure, and they will be left with no one to treat.  Die hard conspiracy  theorists will say "they're funding the trial just to bury it", but if that were true, why fund it at all?  Running a human trial in the US right now, requires public disclosure.  If they really wanted to run some secret trial, they'd be doing it in Russia, China, or some country that didn't have public registry requirements.

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, JDCA, or Tidepool 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.

Friday, May 9, 2014

Four Months of New Studies (Jan-April 2014)

The FDA requires registration of all clinical trials done in the US, or used to get approval for the US market.  Since just about everyone wants to get their drugs sold in the US, this is pretty much a list of all clinical trials.  It is a public database, and I searched it for all new trials starting in the first four months of 2014.  Here is a quick summary:

60 Studies Total
15 - Management of type-1 diabetes carb counting, exercise, etc.
 9 - Artificial Pancreas research and testing
 8 - Insulin testing
 8 - "Interesting" Possible cures for type-1 diabetes.  I will blog on each of these.
 6 - Basic or genetic research
 6 - Complications (this includes 2 tests on Glucagon)
 4 - Equipment (Pump or CGM)
 4 - Non-insulin treatments for type-1.  I might blog on these, if I have time.

This is actually pretty good news because about 13% of the studies are "possible cures".  In the past this number has been closer to 4%, so that's a noticeable improvement.  The interesting trials include these:
  • AAT - Follow on to previous studies (Pathway 5: Inflammation)
  • Beta-O2 - Follow on to a previous case study (Pathway 4: Encapsulated Beta Cells)
  • Secukinumab - First in type-1 study (Pathway 1: Blocking Autoimmunity)
  • Ustekinumab First in type-1 study (Pathway 1: Blocking Autoimmunity)
  • Stem Cells - Implantation of bone marrow stem cells
  • AbATE - Extended data collection for teplizumab trial (Pathway 1: Blocking Autoimmunity)
  • BCG - Dr. Faustman's trial (Pathway 1: Blocking Autoimmunity)
  • ORMID-801 - Oral Insulin (Pathway 1: Training Immunity)

The "Pathway #" come from a report that I worked on with JDCA, which you can read here: http://www.thejdca.org/wp-content/uploads/2014/04/Platforms-Report-.pdf.  It provides a basic overview of how type-1 diabetes might be cured.

The non-insulin treatments include Liraglutide (Victoza) and PF-06342674.

Also, in the past, there has sometimes been a trial so silly it was worth mentioning.  But this time I did not see anything really silly.

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, JDCA, or Tidepool 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.