Diamyd Combo Phase-II Trial Scaled Back

Back in Feburary 2009 I blogged on a very promising clinical trail that was combining the Diamyd treatment to stop the autoimmune attack and two drugs which were already approved for use in the USA.  This is an update for that research.

Diamyd Combo Phase-II Trial Scaled Back 


This Phase II study combines regenerative agents (lansoprazole and sitagliptin) and Diamyd. The regenerative agents are both marketed drugs in the US.  Diamyd is a vaccine like drug which trains the body's autoimmune system not to attack it's own cells.  Sitagliptin (Januvia) is a dipeptidyl peptidase-4 (DPP-4) inhibitor, and is used for type-2 diabetes.  Lansoprazole (Prevacid) is a proton-pump inhibitor (PPI) which prevents the stomach from producing gastric acid. The researchers hope that both lansoprazole and sitagliptin will help reverse beta cell damage or develop new beta cells.

This trial has been scaled back is a big way.  Originally, the researchers were hoping to screen about 160 people and include about 80 of them in the trial.  However, just after the study enrolled it's first patient, there was a major funding cut at NIH (the part of the US government were the study was being done).  At the same time, the primary investigator (Dr. David Harlan) got a new job at UMass at Worster, and so left NIH.  This double setback caused the study to shrink and be redesigned.  

Instead of 80 people in a placebo controlled, randomized trial, they ended up with 3 people in a pilot study where everyone was treated (so no control group).  Now the good news is that the trial is fully enrolled, so they will have all their data by October 2012.  However, the bad news is that the results will be hard to interpret (maybe impossible).  Because this study is using honeymoon type-1 diabetics, there is natural fluctuation in the amount of insulin used.   So with only 3 people and no control group, it will be hard to tell if any improvements are caused by the treatment or random fluctuation during the honeymoon.


Some Personal Opinions


Obviously, I'm hopeful that Dr. Harlan will restart this experiment once he gets settled at UMass Worster.  As far as I know this is the only clinical trail combining a treatment to control the autoimmune attack and a treatment to help the body generate more insulin.  I think combination like this represent one very promising approach to a future cure to type-1 diabetes. It's very disappointing to have it scaled back so much, and for reasons so unrelated to safety or effectiveness.

Clinical Trials site: http://www.clinicaltrials.gov/ct2/show/NCT00837759
NIH page: http://clinicalstudies.info.nih.gov/detail/B_2009-DK-0056.html
Unofficial Diamyd blog: http://diamyd.blogspot.com/

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

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

Tolerx Completes Enrollment in Phase-III Otelixizumab Trial

On Jan 7, 2010 Tolerx announced that they had completed enrollment of their DEFEND-1 clinical trial. This is a phase-III study which is randomized, placebo-controlled and includes 240 patients at over 100 sites all over Europe and North America. Because each patient is followed for a year, we can expect results from this study after January 2011.

The study is designed to evaluate whether a single course of otelixizumab, administered to type-1 diabetics during their honeymoon phase, will preserve insulin production.

Otelixizumab targets CD3 receptor on a T cell.  The hope is that it will work in patients with type 1 diabetes who have residual beta cells by blocking autoimmune attack, while helping the "good" regulatory T cells that protect against the "bad" T cells, thus preserving the beta cells' ability to make insulin.

Press Release: http://www.prnewswire.com/news-releases/tolerx-completes-enrollment-in-defend-1-a-phase-3-type-1-diabetes-study-with-otelixizumab-80892467.html
Corporate Description: http://www.tolerx.com/index.php?page=trx4
Trial's Public Web site: www.DefendAgainstDiabetes.com

Diamyd Will Apply for Approval of Type-1 Treatment in 2011

Diamyd has announced that they expect to file the paperwork for market approval of their GAD65 targeted, type-1 treatment in 2011, after they complete the phase-III trials they have ongoing right now.  Obviously, the headline is great, but remember these things:

• No results from their phase-III trials have been released, yet.  They've got two different large phase-III trials going on right now.
  
• Applying for approval is great, but it usually takes a year or two to get it, after you apply.
  
• The current phase-III trials are all for honeymoon only, and so this approval will be for honeymoon only.
  

Even with all that, it would be great news to have something new approved for honeymoon type-1 diabetes. (Even if the short term result is likely to be just "uses less insulin" or "has longer honeymoon".)  Right now, we have nothing like that.  When they publish their phase-III results, we're likely to see how much of a cure this is likely to be, and for how many people.

Also, you might have seen a HULIQ headline "Approval of Diamyd's Diabetes Vaccine Set for 2011".  That's an outright mistake.  They expect to start the approval process in 2011, not finish it then.  The process takes a year or two to complete.

Press release: http://www.tradingmarkets.com/news/stock-alert/dmydf_swedish-diamyd-medical-to-apply-for-diabetes-vaccine-approval-2011-737987.html

Novo Nordisk Receives US Approval for Victoza (liraglutide) for the Treatment of Type 2 Diabetes 

This really isn't type-1 news by itself, but Liraglutide just got FDA approval, and this is the same drug that just started phase-II trials for type-1 diabetics, and that I reported on in January.  So there are now at least two drugs (the other is Byetta) which are approved for type-2s and causes them to generate more insulin.  If a treatment is found that ends the autoimmune attack, then these treatments might be paired with it to create a faster, more complete cure. 

I'm optimistic about this approach, because there are now four drugs in phase-III trials which are targeted at ending the autoimmune attack, and at least two already approved drugs,  another in phase-III trials, and several more in phase-II trials, which increase the insulin supply.  So those two treatments together might represent a relatively quick path to a cure, if they both pan out and work well together.

News Article: http://money.cnn.com/news/newsfeeds/articles/marketwire/0580389.htm

Transition Therapeutics Announces Results of a Phase 2 Study of TT-223 in Type 2 Diabetes Patients
  
At one time it was hoped that TT-223 would help type-1 diabetics regrow their beta cells and generate more of their own insulin.  However current testing is limited to type-2s (as in this trial).  The good news is that it worked for type-2s: the treated group A1C dropped by about 1.13, while the untreated group dropped by only 0.22.  

To me, this suggests that if we are successful at stopping the autoimmune attack, then TT-223 might be helpful in helping to regrow beta cells.  But so far, there is no evidence that TT-223 would be helpful as a single treatment for type-1 diabetics. 


Press release: http://money.cnn.com/news/newsfeeds/articles/globenewswire/182542.htm

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Hovorka's Aritficial Pancreas Results

Hovorka's Artificial Pancreas Results

Lancet is publishing a paper on Hovorka's AP work.  This work is funded by JDRF (and several European diabetes charities), but is not part of the recently announced collaboration with Animas.

The basic trial was to take 17 kids and teenagers, and have each use a closed loop system while they slept in a hospital (with a nurse double checking that all was well).  One interesting wrinkle was that some of the patients exercised just before going to bed, others ate a large meal, while others did neither.  The idea was to test some situations which would push the AP into tougher situations.  Testing at night and in a hospital is definitely targeting the easiest time of day in the easiest environment. Commercially available pumps and CGMs were used (Smiths Medical, Abbott Diabetes Care, and Medtronic).

I thought the results were good for a phase-II type trial.  Patients using regular pumps were in range 40% of the time during the night.  But when they used the AP, they were in range 60% of the time.  Even better, the regular pumpers went very low nine times, but the APers never did.   So if you want an AP to prevent "dead in bed" situations, then the results were particularly good.

News articles: http://news.bbc.co.uk/2/hi/health/8498993.stm http://abcnews.go.com/Technology/wireStory?id=9752115  http://www.nytimes.com/2010/02/05/business/05diabetes.html
Abstract: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961998-X/fulltext
Trial Record: http://controlled-trials.com/ISRCTN18155883

Joshua Levy

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.