Diamyd Fails in Phase-III Trial

Diamyd Fails in Phase-III Trial

Diamyd's European phase-III trial has failed. The official quote is "did not meet the primary efficacy endpoint". Basically, the the people who got the drug did not do better than those who did not, in the the most important measurement of success. The primary endpoint for this experiment was C-peptide generation, which is a marker for natural insulin production. Basically, they were hoping that giving this drug would help honeymoon type-1 diabetics generate more of their own insulin, but it did not.

(By the way: if that paragraph sounds familiar, it's because its the exact same paragraph that I used to describe Tolerx's Otelixizumab failure a few weeks ago, and could have been used to describe MacroGenics's Teplizumab failure a few weeks before that. It applies pretty much the same to all three. They all failed in about the same way and at almost the same point in their development cycle.  They were all in phase-III clinical trials.)

This is a vaccine like treatment designed to teach the body's own immune system to stop attacking it's own beta cells. You can think of it like the anti-alergy injections that people sometimes get. They give a little of the allergen so that the body slowly becomes used to it. The company's description is this: "with Diamyd® is thought to induce tolerance to GAD, thereby intervening in the autoimmune attack and preserving the capacity to produce insulin in patients with autoimmune diabetes".

Where is Diamyd Now?

The situation for Diamyd is a little more complex than for ToleRx or MacroGenics, because there are more different studies being done with Diamyd's drug than for ToleRx's or MacroGenics's drugs, and those studies are being done by more different people.  Diamyd is planning to continue their large phase-III trial in the US, which is basically a twin of this trial that failed.  And they are also going to continue following the patients in this trial, just in case there are good results after a longer period of time.  I don't hold out much hope for either of those studies being successful.

Additionally, there is at least one study which is using Diamyd to try to prevent type-1 diabetes by giving it to people who have not yet been diagnosed.  There is at least one phase-II study being done by academics in the US (so not run by Diamyd).  Finally, there is a very small "combo" study being done at the NIH where Diamyd is being combined with two other drugs to try to either regrow beta cells, or get more insulin out of the existing beta cells.  The hope is the combination of all three drugs might impact type-1 diabetes.  I expect all three of these trials to continue, and they are all a little different from the one that failed, so there still is some hope.

So Where are We Now?

I think everyone needs to understand that these last six months have been disastrous in for human trials designed to lead to a cure for type-1 diabetes.   We've gone from having 4 drugs in phase-III trials -- the last phase before market approval -- to having just 1.  The remaining one is DiaPep277.  On average, a drug which enters phase-III trials should successfully move to the next stage (market approval) about 55% of the time.  In fact, for type-1 diabetes we are currently somewhere between 0% and 25% (the higher number only if DiaPep277 eventually gets approved).

Also, it is disturbing to note that no new drugs have started phase-III trials in the last two years.  We have gotten new phase-I and phase-II drugs, but nothing has entered phase-III trials to take the place of the three that have dropped out.  That's a bad sign as well.

I'm not sure the proper musical background for this blog entry, but definitely something by Nine Inch Nails,  maybe "Something I Can Never Have".

You Won't Hear It Here, First
I was talking on the phone to a research analyst months ago, and he as me "how do you know all this research news before anyone else".  I was so shocked, I almost dropped the phone.  Because it's not true.  Almost never am I the first person to publish something in my blog.  Why not?  First, because I'm in California.   That means if something happens in Europe or the East Coast, local bloggers will be posting about it hours before me.  But the big reason is that I'm not trying to to be quick; I'm trying to provide context and thoughtful reflection on the news.  I'm not trying to be news clipping service.  My own goal, is to blog on important events within a week of when they occur, and more minor events within a month.  But I don't always succeed even at that.


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. 
Blog: http://cureresearch4type1diabetes.blogspot.com
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Orban's Phase-I Results

I'm a little embarrassed that it has taken me so long to blog about Dr. Orban's results.  They were announced almost a year ago.


Data from Orban's Phase-I Trial

This research is a vaccine-like attempt to teach the body's immune system to stop attacking it's own beta cells.  A molecule (insulin B chain) similar to insulin was given along with IFA (an adjuvant, a chemical that makes the immune system react more strongly to a vaccine) to try to train the immune system not to attack beta cells.  This was a single injection during the honeymoon phase and patients were then followed for two years.

In terms of safety, the results were fine: nothing bad happened, and this is a new treatment, so safety was an important question.  But in terms of effectiveness, the results are mixed.  The vaccine did result in a specific immune system change that looks promising.  The exact quote was:

The induction of a lasting, robust immune response generating autoantigen-specific regulatory T cells provides strong justification for further testing of this therapy in type 1 diabetes.

But no effectiveness was seen during the trial.  Their was no improvement in C-peptide generation of the treated group compared to the non-treated group.  They were checked every six months.  Dr. Orban works at the Joslin center.

Opinions

In my mind how you view these results says a lot more about your personality, than the results themselves.  If you are an optimist, then you say "they proved safety, and they proved the treatment induced the change in the immune system the researchers were looking for so this is a success, and they should move on to phase-II testing to find a dose that will have a good effect on the person".  If you are a pessimist, then you say "it did not effect the patient's C-peptide numbers, so there is no reason to think it will end up curing (or even improving) type-1 diabetes".  The American phrase for this dichotomy  is "Is the glass half empty or half full?"

But the truth is, that my opinion doesn't matter, and neither does your's.  (Unless you happen to be funding Dr. Orban, of course!)  If Dr. Orban gets funded for the next phase, then this study is a success on a path that might lead to a cure.  If not, then it is a failure.  That's not a very scientific view of success, but it is very pragmatic.

In the past, I know that ITN has discussed the possibility of doing a phase-II trial, but nothing ever came of it.  I don't know why.  Also, Dr. Orban has started his own company, specifically to bring this cure to market.  Their web page is here: http://www.orbanbiotech.com/

The most recent news I have have from them is that in Nov 2010 they got a grant from the US Government: http://www.marketwire.com/press-release/orban-biotech-awarded-244000-qualifying-therapeutic-discovery-grant-from-us-government-1354039.htm
"Orban Biotech Awarded $244,000 Qualifying Therapeutic Discovery Grant From U.S. Government"
Abstract: http://www.ncbi.nlm.nih.gov/pubmed/19931408
Summary: http://www.immunetolerance.org/studies/autoantigen-vaccination-newly-diagnosed-type-1-diabetes-mellitus
Full Paper: http://www.immunetolerance.org/sites/files/2010.04_Orban_JAutoimmunity.pdf
(Thank you Immune Tolerance Network!  For making this available on your web site.)
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00057499

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.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials