Friday, October 2, 2015

Summary of EASD 2015


EASD is the European Association for the Study of Diabetes.  Their conference is the largest diabetes research gathering in Europe.  I did not attend, but reviewed all the abstracts, posters, and 100s of tweets sent with the EASD2015 hashtag.  This posting is my summary.

Unfortunately, as with ADA 2015 earlier this year, there was not much research aimed at a cure which had reached human trials.  I've divided this posting into four areas: news on human trials aimed at a cure, artificial pancreas research, high buzz research, and other research I found interesting.  But there was only one abstract dealing with a cure in human trials.  Disappointing.

Research In Human Trials Aimed At A Cure

Proinsulin peptide immunotherapy in type 1 diabetes: safety data of a first in new-onset type 1 diabetes phase 1b trial || Abstract #503
http://www.easdvirtualmeeting.org/resources/proinsulin-peptide-immunotherapy-in-type-1-diabetes-safety-data-of-a-first-in-new-onset-type-1-diabetes-phase-1b-trial--2
These researchers are testing a type-1 diabetes vaccine made from part of an insulin molecule.  They are testing it for safety in newly diagnosed type-1 diabetics.
The poster is not on line, but you can see the abstract.  It appears that the study was strictly safety-only, and there were no safety issues, but no data on effectiveness, either.

Artificial Pancreas Research

There was a lot of AP research.

This was a presentation by the Cambridge group:
http://www.easdvirtualmeeting.org/resources/twelve-week-unsupervised-day-and-night-closed-loop-insulin-delivery-during-free-daily-living-in-adults-with-type-1-diabetes-a-multicentre-randomised-cross-over-study--3
33 adults used an AP for 12 weeks "free range".  Trial was open label, cross-over design.  (Meaning that all patients were both treatment group and control group at different times.)  AP did not handle meals.  AP did better than non-AP in terms of average BG, and no worse for lows.  AP also did better on A1c.  This research was published in the New England Journal of Medicine:
http://www.nejm.org/doi/full/10.1056/NEJMoa1509351
and is also discussed here:
http://www.clinicalendocrinologynews.com/specialty-focus/diabetes/single-article-page/artificial-beta-cell-insulin-systems-post-more-positive-data/8e1e8f69192b2d3f1dc40f418cffb9a6.html
and here:
http://www.medpagetoday.com/MeetingCoverage/EASD/53621

This was a presentation by groups in France and Italy using the University of Virgina AP:
http://www.easdvirtualmeeting.org/resources/hba1c-improvement-with-less-hypoglycaemia-in-patients-with-type-1-diabetes-wearing-an-artificial-pancreas-for-two-months-from-dinner-to-breakfast
35 adults used an AP overnight for two months. Trial was cross-over design.  AP did better than non-AP in terms of time in target, with less time in both high and low BG.
One patient dropped out of this study because he was not able to trust the device enough to participate in the study.  This patient was a professor of mathematics.  (This got a laugh during the presentation.)
These researchers are now testing 24 hour use of the device.

This presentation was by Steven Russell on the Bionic AP (same project as Dr. Damiano works on):
http://www.easdvirtualmeeting.org/resources/the-bionic-pancreas-when-will-the-dream-come-true
This presentation included previous data from adults and camp kids, but also new (to me) data from younger children (6-11 years old).  This was also at camp, and was 5 days on, 5 days off (cross-over design).  The BG improvements seen in these younger kids was better than seen in adults or in camp kids.  In my opinion, the improvements seen in these kids were striking.

He then presented data from a "free range" trial of 40 adults for 11 days on, and 11 days off (cross-over) study.  This data was also very good.  The whole presentation was well done, and well worth viewing, but if you just want some quick data: fast forward to slide 25 (usual care) and then compare it to 26 (AP); this is for one selected patient, but you can see the huge improvement.

He then presented data from a comparison of glucagon vs. no glucagon study.

Finally he presented their target (hoped for) timeline:

  • Transitional Studies: 2013 - 2016
  • Production of a fully integrated device (prototype already made via private donations).
  • Bridging Studies: starting in 2016
  • Pivotal Studies: 2017 - 2018
  • Review by FDA: 2018
  • Commercial availability: late 2018 or early 2019


Dr. Russell said that the FDA had indicated that this device and long term glucagon use, could be approved based on a single pivotal trial of 450 patients for 6 months, with a 6 month extension for 100 of the patients.  (And this length and size is due to the needs of the glucagon approval.)

Also, Tidepool is collaborating with this research team in creating the user interface for their AP.

High Buzz Research

The research which generated the most buzz, by far, was the results of the EMPA-REG study.
However, this was a huge study of a SGLT2 drug in type-2 diabetes, so I won't comment.

There were also a lot of "Insulin vs. Insulin" and "New Insulin" papers and posters.  These are studies which show that one type of insulin is better than another, or that a new type of insulin is safe and effective.  I didn't count, but suspect there were over 20 of them, but this kind of research does not excite me.  There was some early work on a weekly shot basal insulin, and that is interesting to me. The research was on people, too.  But it is still years off, I think.

Glucagon nasal powder: an effective alternative to intramuscular glucagon in youth with type 1 diabetes (Abstract #42) generated some buzz:
http://www.easdvirtualmeeting.org/resources/glucagon-nasal-powder-an-effective-alternative-to-intramuscular-glucagon-in-youth-with-type-1-diabetes--2
You can watch the 15 minute presentation or read the abstract, at this web page.
Slide #5 shows clearly that glucagon nasal powder is similar to glucagon injection.
This tweet contains a one chart summary: https://twitter.com/jgryan0/status/643779712385478656
Patients in this study were between 4 and 17 years old; a previous study had focused on adults.
The nasal formulation was much easier to use, and (of course) no needle was needed.  Also the same nasal dose can be used for youth of all ages, so no more "half shots" for younger/smaller kids.
One patient sneezed immediately after getting the nasal glucagon, and this patient's BG levels did not rise, but the researcher wasn't worried because glucagon is usually given to unconscious people, who don't sneeze.  The company involved (Locemia Solutions) is "in discussions with regulatory agencies".

There was a phone app (I think called "gocarb") where you took a picture of a plate of food, and it estimated carbs.  Here are some of the tweets for that:
https://twitter.com/sugartweaks/status/643400361588465664?ref_src=twsrc%5Etfw
I'm a little dubious about this whole idea, but it did generate a lot of positive tweets.

Dexcom's G5 will soon be available in Europe:
https://twitter.com/danielvegh/status/643770125095706624

The Google/Dexcom tiny BG sensor also generated some buzz:
https://twitter.com/diaTribeNews/status/643339894522142720?utm_source=fb&utm_medium=fb&utm_campaign=sciencehorse&utm_content=643759843656884224


Other Research I Found Interesting

The talk by Andrew Hattersly:
http://www.easdvirtualmeeting.org/resources/insights-into-the-beta-cell-from-patients-with-monogenic-diabetes
This is a one hour talk given by Dr. Hattersly, who basically discovered monogenic diabetes (often called MODY).  I really enjoyed it, even if I did not understand all of the science.  The talk is good because it shows how different scientific work comes together to make important discoveries, and how science is a team effort, and patients are involved.  Monogenic diabetes  is caused by a single genetic mutation.  There are several different types of monogenic diabetes , each involves the mutation of a different single gene.  This is quite different than classic type-1 diabetes, where there are many genetic features, some of which make type-1 more likely, some less likely, plus environment triggers, all of which come together to cause type-1 diabetes.  Monogenetic is binary: you have the gene, you get the disease.

The key points from this talk are two fold:

  1. Anyone diagnosed with type-1 diabetes when they are under six months of age, actually has neonatal diabetes (one form of monogenic diabetes ).  Neonatal diabetes can be treated with insulin, but can also be treated with a much cheaper pill (no shots!)  If you, or someone  you know, was diagnosed when less than six months old, and uses insulin, you (or they) may want to talk to your doctor about trying to switch to the pill.  More information: http://www.diabetesgenes.org/content/neonatal-diabetes
  2. Dr. Hattersly estimates that between 1% and 3% of the people diagnosed with type-1 diabetes actually have some form of monogenitic diabetes. Except for neonatals, these people generally must be treated with insulin, just like type-1s, but it's still valuable knowledge.  He has an experimental web page to calculate a person's chance of having monogenic type-1 diabetes: http://www.diabetesgenes.org/content/mody-probability-calculator


Autoimmune diseases in children and adults with type 1 diabetes from the type 1 diabetes exchange clinic registry || Abstract #499
http://www.easdvirtualmeeting.org/resources/autoimmune-diseases-in-children-and-adults-with-type-1-diabetes-from-the-type-1-diabetes-exchange-clinic-registry--2
This link has an abstract, the poster, and a 5 minute discussion by the author.
The Type 1 Diabetes Exchange is a huge project, funded by the Helmsly trust, to gather all kinds of data on over 25k people who have type-1 diabetes.    Some findings:
The #1 additional autoimmune disease found in type-1s is thyroid disease at 19%.
Celiac's is #2 at 6%.


Sustained glycemic control and less nocturnal hypoglycemia with new insulin glargine 300 U/ml versus glargine 100 U/ml over 1 year in Japanese people with type 1 diabetes mellitus (EDITION JP 1) || Abstract #4http://www.easdvirtualmeeting.org/resources/sustained-glycaemic-control-and-less-nocturnal-hypoglycaemia-with-new-insulin-glargine-300-u-ml-versus-glargine-100-u-ml-over-1-year-in-japanese-people-with-type-1-diabetes-mellitus-edition-jp-1--2
ADA 2015 had at least one paper (which I found interesting) suggesting that higher density insulins were better for type-2 diabetics.  Some extremely obese type-1 diabetics need to refill their pump every day with standard u100 insulin, but only every other day with u300 insulin.  This is a money and convenience issue.  But additionally, there was evidence that higher density insulins were more effective; that fewer units were needed for the same carb or basal situations.  This study found that type-1s used more insulin, but had lower nocturnal numbers and at the same time, fewer lows.  That's still a good outcome.

I found the comparison to u100 to higher density insulins interesting, especially if we get sets that can last longer than 3 days, the pressure for high density will become stronger.

Joshua Levy
http://cureresearch4type1diabetes.blogspot.com public
joshualevy 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.

3 comments:

Diane Roth said...

Hello,
Above you mentioned you were disappointed there was only 1 human trial going on to cure type 1 diabetes. I just learned of the Phase II human clinical trial just approved by the U.S. FDA in June 2015 at Massachusetts General Hospital. Their goal is to complete enrollment and fund raising by the end of 2015. Was this trial and its potential for a real cure discussed at the above mentioned diabetes research gathering?
Diane Roth

Joshua Levy said...

There were no presentations on the Phase-II clinical trial being done at Mass General. That same group did present a poster and a 15 minute talk on low levels of C-peptide and its value in long term type-1 diabetics. You can see and hear those here:
http://www.easdvirtualmeeting.org/resources/persistence-of-c-peptide-secretion-and-impact-on-health-in-advanced-type-1-diabetes--2
http://www.easdvirtualmeeting.org/resources/low-levels-of-c-peptide-production-protect-from-complications-and-improve-hba1c-control-in-longstanding-type-1-diabetes--2
but neither deal with a cure.

As for the trial having a "potential for a real cure", as long as trial is going on, there is always hope. That trial is scheduled to publish results in 2022 at the earliest, so I'm looking forward to seeing those results, then. In my experience the best predictor of the success of the phase-II trial is the results from a phase-I trial (if any). In this case the phase-I trial was unsuccessful, so that plays into the odds of the phase-II being successful.

Joshua

Lars, Profil said...

Hi, you mentioned the AP@home artificial pancreas coverage.
We were part of the study and posted a blog here.
http://blog.profil.com/blog/longest-at-home-free-living-closed-loop-study-so-far

Also in German media there was major coverage on this project.

Best,
lars