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.

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

MicroCHIPS Will Start phase-I Trial of new CGM (and gets 16+ million)

For people interested in the artificial pancreas project, MicroCHIPS just got about 16 million dollar investment, and one of the things they will do with that money is start a phase-I study later in 2010 on their CGM technology. Here is their description of why their technology is better than current technology:

MicroCHIPS hopes their product will last months, or even years, and their main innovation is to create the implant with a differently-built sensor. Current devices, Pax says, have a single sensor that can only detect glucose levels until it runs out of the sensing chemical. But the MicroCHIPS device employs a redundant array of sensors, with each one becoming active as needed.

And the part that interests me the most is this:

MicroCHIPS intends to conduct initial clinical testing in 2010 to advance its diabetes program.

Some Discussion

I think it is clear that CGM technology is the weakest component in current artificial pancreas research. However, a CGM technology that lasted 3 months or more in the body would be a huge improvement in this area. So I'm excited by this technology, and am looking forward to seeing how well it works. One of the new funders is Medtronic. Since Medtronic already has cutting edge commercial CGM technology, they are not expecting more of the same: they are expecting better than they have. So I think it is fair to expect that whatever MicroCHIPS is creating, it is a lot better than we have now.

Press Release: http://www.mchips.com/10_Jan_07_pr.html
News Article: http://www.dotmed.com/news/story/11267/

Novo starts phase-II Clinical Trial of oral GLP-1

Novo Nordisk (one of the largest pharma companies targeting type-1) is working with Hvidovre University Hospital in Denmark to test an pill version of Victoza (generic: Liraglutide) which is a GLP-1 receptor agonist. They are specifically targeting type-1 diabetics in this study. Technically a phase-II trial (because the drug is already approved), it will enroll about 30 people, and be completed by second half of 2010.

A Little History

Several treatments leveraging GLP-1 have been tried over the years as GLP-1 related drugs help the pancreas generate more insulin. They are usually targeted at type-2 diabetics, who have a lot more useful pancreas to work with. Byetta is the most famous GLP-1 analog used by type-2 diabetics. Of course, the question here is: will it help people with type-1 diabetes?

Some Discussion

This is right on the edge of what I consider a possible "cure". It seems unlikely to me that any treatment that works by causing the pancreas to generate more insulin will -- by itself -- result in a cure for type-1 diabetes. However, I'm reporting on this because it might turn out to be part of a cure. For example, by combining it with Diamyd's, ToleRx's or MacroGenic's treatments (all in phase-III clinical trials, and all of which prevent/weaken the autoimmune attack) .

The injected form of this drug (Victoza) was approved for use in the EU in 2009, and is marketed in at least three countries (UK, Denmark, and Germany). However it has not been approved in the US, because of worries about thyroid tumors. The US FDA review was in April 2009.

If this drug turns out to help type-1 diabetics, then (in addition to Byetta) there are two other similar drugs, each being developed by a different drug company, which may also help type-1 diabetics: albiglutide and taspoglutide.

Press Release: http://www.reuters.com/article/idUSLDE60C0CB20100113?type=swissMktRpt
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00993720
Wikipedia: http://en.wikipedia.org/wiki/Liraglutide

News (but no Announcement) from Faustman

Although Faustman's team has not made an official announcement (at least not one that I've seen), they did reopen enrollment in their phase-I BCG clinical trial, after having closed it last February. Without information on why they did this, there is no way to know if this is good news or bad, or if it will cause a delay in reporting their phase-I results. Although you'd think if it was good news they would have had an announcement.

This is the timeline: In Feburary 2009 they updated their clinical trial record to show that they had finished enrollment in their phase-I trial. In mid 2009 they announced that their results would be published in early 2010, and specifically would be turned over to their internal statistics group in November of 2009. However, in October 2009 they updated their clinical trial record again to show that they were once again enrolling patients in the study. Right now, their web site says specifically they are NOT enrolling new patients, but their Clinical Trials web page says that they ARE enrolling new patients.

What might this mean? The best possible news would be that they are trying to do more with their phase-I trial than originally expected. LCT did this for their trial in Russia. Once it was underway, they updated it to include more people and bigger doses. If the BCG team is trying the same thing, that would be good news.

The worst news would be that they did some early data analysis of their results, and found they did not have statistically significant results. So they added more people to the study in the hopes of getting a statistically significant result. The DiaPep227 guys did this with their phase-III study.

Middle of the road news would be that some of their samples or data got lost, mislabeled, or a patient pulled out at the last minute or something. So they need some more patients to enroll, and might have a delay, but nothing really bad. Something like this happened to Diamyd's phase-II LADA trial.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00607230

JDRF, J and J's Animas Corp, and DexCom Start Joint AP Project with Clinical Trial this Year

For people interested in the artificial pancreas project, there was a big announce from JDRF of a joint project with Animas (pump makers, and a division of Johnson & Johnson), and DexCom (CGM makers). It's been widely publicized, so I won't go into details. To me, the most interesting part was this:

The first patient testing could begin in less than a year, Kowalski said.

and that is good news, especially since most phase-I AP testing can be done quickly. We should start seeing clinical trial results on this AP combination maybe by end of this year, but more likely sometime next year.

News Article: http://abcnews.go.com/Business/wireStory?id=9550823

Joshua Levy