Background on the drug: Rituximab targets the CD20 part of the immune system's B cells (different from the pancreas's beta cells) to try to prevent the autoimmune attack. B cells are part of the body's immune system and communicate with the T cells, which actually attack the body's beta cells in the pancreas. By targeting the B cells, it is hoped this treatment will stop or lower the attack of the T cells. Rituximab showed some effectiveness in preserving the beta cell function of honeymoon type-1 diabetes in a phase-II trial, and there is a second trial underway. Rituximab is a monoclonal antibody, a product of Genetech (now a division of Roche), and already approved by the US FDA for rheumatoid arthritis and several cancers (and used off label for several other diseases).
Background on antibodies: Type-1 diabetes is triggered when the body's own immune system attacks it's own beta cells in the pancreas, which create insulin. Autoantibodies are part of the process of this self-attack. In type-1 diabetes four different types of autoantibodies have been measured: GAD, Insulin, IA2, and ZnT8. There might be a few more autoantibodies that we don't yet know about. People with type-1 diabetes usually have one or more autoantibodies in their system, and this starts before they are diagnosed. I think that GAD is the most common, and IAA is second, but I'm not up on the details.
For this study, 49 patients where given four doses of Rituximab, while 29 got the placebo. For all patients, measurements were made for each different type of autoantibody. What they found was that Rituximab was very good at lowering IAA autoantibodies, but much less effective on the other three known types of autoantibodies. This was the biggest finding:
A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients.So that means that Rituximab was highly selective as to what antibodies it shut down. This is a very interesting finding, at least for me. In terms of impact on patients, we need to see the C-peptide numbers, which were not in the abstract.
In light of these results, one obvious clinical trial to run would be to treat honeymoon type-1 diabetics, who only have autoantibodies to IAA, with Rituximab, and see what happens. The results above imply that over a third of these patients would end up having no autoantibodies remaining, and it would be very interesting to see what happens to these patients. What effect will it have on their insulin production? Will they still have type-1 diabetes? Will their pancreases regrow? If so, how quickly? These are critical questions.
Another interesting clinical trial to run would involve patients that did not have type-1 diabetes, but were being tracked by TrialNet's Natural History Study, and are known to only have IAA autoantibodies. Basically, does treating these specific people with Rituximab delay or reduce the onset of type-1 diabetes?
And finally, there is a potential study for established type-1 diabetics who only have IAA antibodies. Would giving them this drug have good effects?
I have no idea if any studies like these are feasible, or are being planned, but I hope so!
News article: http://www.doctorslounge.com/index.php/news/pb/22439
More on Autoantibodies: http://www.msdlatinamerica.com/diabetes/sid683880.html
News about News on DiaPep277
DiaPep277 is the longest running phase-III study aimed at curing type-1 diabetes. It is a honeymoon only treatment. Results from the phase-II study were (in my opinion) "mixed". (I know that doesn't sound very definitive and I really should go back and review their phase-II results in more depth, but I haven't had time.) My most detailed discussion of their phase-II results is here, but it's not much:
and all of my blogging on DiaPep277 (hsp60) is here:
The following quote is from a news article on them, and is the most recent news I have heard about when they might have some phase-III results. The key news is that the study should be done late this year, which is not very far away. With a little luck, we'll see results in 2012.
In the first Phase III studies being conducted at 40 medical centers in Europe, South Africa and Israel, diabetes patients aged 16 to 45 have been receiving DiaPep277 injections once every three months. The study began in 2005 and is ending late this year.They have a second phase-III study already underway, and expected to finish in 2014. (Remember, you need two in order to get FDA or EU approval.)
News coverage: http://www.shalomlife.com/health/15810/promising-treatment-for-diabetes/
Rilonacept is Recruiting for a Phase-I Trial
I know there is a lot of frustration about studies that are targeted at "honeymoon" diabetics. And it is certainly true that most current trials are aimed at honeymooners. However, "most" does not mean "all". Dr. White is running a study on Rilonacept that is open to people within 5 years of diagnosis. Also, this study has no placebo group, so if you are in the study, you know you are getting the treatment.
I have previously blogged on this clinical trial, which you can read here:
This drug is already approved in the US under the trade name "Arcalyst", but not for type-1 diabetes. In addition to this approval, it is currently being used in about 12 other clinical trials for a variety of inflammation related diseases. Dr. White has told me (via email) that there have been "no untoward effects thus far". The trial is being run in Dallas, Texas. Contact information is in my previous blogging (link above).
Trial web site: http://www.childrens.com/specialties/endocrinology/rilonacept-study/
Clinical Trial Site: http://www.clinicaltrials.gov/ct2/show/NCT00962026
Some Background Reading
Below is a link to a short interview with Dr. Arthur Caplan, a bioethicist at University of Pennsylvania, which makes for some interesting reading. It is about the ethics of overseas medical research. Something that we are seeing a lot of in type-1 diabetes research. Dr. Caplan is an interesting guy and a good speaker. UPenn is my alma mater:
The following Wikipedia article covers accuracy of home glucose monitors. Many people are shocked to learn that they are only accurate to within 20%. So you might get 310, 340, or even 360 at the same time: http://en.wikipedia.org/wiki/Clarke_Error_Grid
Thanks to swellman at CWD for pointing this out to me and many others.
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.
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news