Current Research into Cures for Type-1 Diabetes: Anakinra

Showing posts with label Anakinra. Show all posts

Sunday, April 28, 2013

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

Unfortunately, this is bad news. But here it is:

Canakinumab and Anakinra Both Fail Phase-II Trials in Honeymooners

Canakinumab (brand name Ilaris, previously known as ACZ885) and Anakinra (brand name Kineret) are different drugs, but they have a lot in common. Both target IL-1, which is part of the immune system. Canakinumab is already approved in the US for the treatment of cryopyrin-associated periodic syndromes. Anakinra is already approved in the US for the treatment of rheumatoid arthritis. Unfortunately, both failed Phase-II trials for type-1 diabetes. Here is the quote from the abstract:

Canakinumab and anakinra were safe but were not effective as single immunomodulatory drugs in recent-onset type 1 diabetes.

A previous, smaller test of Anakinra had also failed.

Discussion

I occasionally hear arguments that testing drugs on NOD mice is the wrong approach. That we should not bother to do that, and just go straight to human testing. People who make this argument are quick to point out that NOD mice are commonly cured of type-1 diabetes, but none of these cures have worked in people. They often go a step farther and suggest that maybe NOD mice are so different that they are leading researchers astray. That a successful mice cure means it won't work on people, and conversely that drugs that work on people might not work on mice.

However, both of these drugs were tested initially in people. They were never tested (alone) in NOD mice. And they both failed. Of course, two examples don't prove anything. However it does support the idea that curing type-1 diabetes is tough no matter if you test first in mice or first in people.

Abstracts:

http://www.lancet.com/journals/lancet/article/PIIS0140-6736%2813%2960023-9/abstract

http://www.ncbi.nlm.nih.gov/pubmed/21518168?dopt=Abstract

Clinical Trial Records:

http://clinicaltrials.gov/ct2/show/NCT00947427

http://clinicaltrials.gov/ct2/show/NCT00711503

http://clinicaltrials.gov/ct2/show/NCT00645840

Wikipedia:

http://en.wikipedia.org/wiki/Canakinumab

http://en.wikipedia.org/wiki/Anakinra

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. Thanks to everyone who helps with the blog.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

Saturday, April 4, 2009

Two New Trials to Test Kineret / Anakinra

I recently found out about two clinical trials into the drug Kineret also known as Anakinra (an Anti-Interleukin-1 treatment). A phase-I study which started in March 2008, and a phase-II study which started in January 2009. Last year there was some interest in the idea that inflammation was a causative factor in type-1 diabetes. These are the first human trials that I know of which are based on attacking inflammation to try to cure type-1 diabetes (in honeymooners only, however). This drug is already approved by the US FDA for the treatment of rheumatoid arthritis. It has also already be used in clinical trials focusing on type-2 diabetes and some autoimmune diseases (in addition to RA).

The phase-I study is 15 kids (aged 6 to 18) who are within one week of diagnosis. The trial is scheduled to end in July 2009. It is being done by Soumya Adhikari at Children's Medical Center Dallas, Texas, United States, and is funded by their own foundation. You can read the US Clinical Trail Record here: http://clinicaltrials.gov/ct2/show/NCT00645840. I can find no other information on this trial on the web.

The phase-II study is being done by the Steno Diabetes Center in Denmark is testing using Kineret on newly diagnosed type-1 diabetics. The study is called "AIDA". It is multi-site, all in Europe. You can read more about it here: http://www.aidastudy.org. The study is funded by JDRF, Steno, and Oresund.

This is their description of the drug:

Kineret® is already being used in the treatment of patients suffering from arthritis and studies are now suggesting that it may also be useful for patients with Type 1 diabetes. The active substance in Kineret is interleukin-1 receptor antagonist, a blocker of an immune-signal molecule named interleukin-1. During inflammation this blocker is produced by your body to limit tissue damage caused by inflammation, and kineret is an exact copy of this naturally occurring molecule.

The study will use 160 patients, starting in January 2009 and ending (they hope) in September 2011. Half will get the drug, half placebo. After 80 patients have been followed for 6 months, they will do analysis on the available data, and decide if it is worth continuing the trial, and if it is safe to do so. I don't know if this interim analysis will be published or not. (I hope so!)

Patients will inject themselves once a day, for two years, so this is a pretty big commitment on their part. Since patients must be 18 or over, and with in 12 weeks of diagnosis, I suspect it will take them quite a while to enroll 80 people, even as they have 23 sites participating. Although the fact that it is using an already approved drug should make it easier to recruit.

The US Clinical Trial Record for this is NCT00711503, which you can see here: http://www.clinicaltrials.gov/ct2/show/NCT00711503

There is more information on the Steno center here: http://www.stenodiabetescenter.com/documents/home_page/document/index.asp

If you are newly diagnosed (less than 12 weeks), and in Europe, here is a list of trial sites:
http://www.aidastudy.org/centers/index.htm

A Little Discussion

Everyone knows that type-1 diabetics have a lot of inflammation in their pancreas and especially around their beta cells. Most researchers believe that inflammation is a result of the body's immune attack on it's own cells. That is, the underlying immune problem causes inflammation and also causes beta cells to die (which causes the symptoms of type-1 diabetes). However, some researchers believe that the underlying immune problem causes inflammation, and that this inflammation kills the beta cells, which causes the symptoms of type-1. The difference is that, in the second model, if you stop the inflammation you can stop the symptoms of type-1 diabetes (the high BG numbers and the low numbers). And that is a big difference. But this second model is still a minority opinion.

The treatment being tested should lower inflammation, so if the second model is correct, it will lessen the symptoms of type-1 diabetes, maybe remove the symptoms entirely: the body will naturally produce more insulin. In any case, one of the great things about this research, is that we should have some solid data soon. The phase-I trial should complete mid this year, the early data from the phase-II later this year, and the final data from the phase-II by year after next.

Joshua Levy

This blog discusses cures and preventatives for type-1 diabetes that are either in human trials or just about to start. Treatments for diabetes are not generally discussed here, unless they can turn into a cure or a preventative. My definition of a cure is this:
1. Blood sugar control without testing and with doctor's visits 4 times a year, or less. Any cure must result in an average lifespan close to normal.
2. Does not require a lifetime of immunsuppressive drugs, so it is not trading one treatment for another. (but a couple of operations, or a short course of drugs is OK)
Obviously, this is my personal definition of a cure; yours may differ.
Because a cure for type-1 diabetes is likely to involve a combination of several different drugs or treatments, I try to follow research into anything which may be an important part of the cure.

My Non-Conflict of Interest Statement

For the first 10 years of running this blog, I did not work for a company doing medical research. In 2018, I started working for Bigfoot Biomedical, which is developing an "automated insulin dosing/delivery solution" (what many call an Artificial Pancreas).
I blog on research aimed at curing type-1 diabetes, and I view Bigfoot Biomedical's work as treating type-1 diabetes (not a cure at all). Therefore, I don't view this work as conflicting with my blogging. However, if you consider the kind of automated insulin dosing/delivery solution that Bigfoot is developing to be an actual cure for type-1, then this would conflict with my blogging. I think they are quite different.
I don't get paid in any way by any company working on a cure for type-1 diabetes; I never have. And that includes free samples, free travel, or free anything. I do sometimes participate in market research studies or focus groups, and they sometimes pay.
None of the hours that I have put into my blog, or the posts that I make to any web site, has ever been paid for. (Except for some very nice and heart felt thank-you emails, and those are worth more than money.)
My daughter has type-1 diabetes and participates in clinical trials. I sometimes report on trials that she participates in, but I do not reveal her participation because I consider her medical history to be private.
I sometimes "beta test" new software or devices involved in type-1 diabetes. When I'm blogging about something where I have been given special access, I say so.
In the past I have volunteered with JDRF and The NIIB Project. I currently am a fellow with JDCA. The JDRF and NIIB work was completely unpaid. JDCA has given me equipment that I use to help my blogging, and on one occasion paid for specific consulting work.