Thursday, September 24, 2009

Two Possible Cures go to the Boneyard

It's never good news when possible cures "go to the boneyard", but it is part of research. Some treatments work and many don't. Here is a little discussion of two treatments, one of which has not worked out (for type-1 diabetes), and the other is on hold, with no clinical trials in sight:

Transition Therapeutics's TT-223 goes to the Boneyard

Transition Therapeutics is researching using a combination of two drugs to cause beta cell regrowth in an attempt to cure type-1 and type-2 diabetes. As of May 2009, they had officially marked their phase-I human trial for type-1 diabetes as closed. I haven't seen any published results for it, but I'm still looking. However, actions speak louder than words, and Eli Lilly (working with Transition Therapeutics) started a clinical trial in February 2009 using Transition Therapeutics's TT-223 product, but only for people with type-2 diabetes.

Also, in May 2009 they announced that JDRF and Transition Therapeutics had agreed that JDRF would stop funding clinical development of TT-223. Transition Therapeutics and JDRF terminated their agreement. Eli Lilly is taking over support for TT-223, but is applying the technology only to type-2 diabetes.

So the news from Transition Therapeutics for type-1 diabetics is not good. I will move Transition Therapeutics to my "boneyard" of research that has not panned out if there is no good news in the next 6 months.

Discussion

This result is not too surprising, and is similar to previous results with INGAP: because type-1 diabetes is an autoimmune disease, simply regrowing new beta cells can not cure it. The immune system attacks the new beta cells the same as the old ones. This type of treatment has more direct applicability on type-2 diabetes, where more beta cells are more likely to be helpful. Of course, if any of the treatments currently being developed succeeds in ending the autoimmune attack, then treatments that regrow beta cells will suddenly be in high demand. Unless the body regrows beta cells naturally without intervention.

A few months after stopping the funding of TT-223, JDRF started funding a large, general program (together with Genomics Institute of the Novartis Research Foundation) to test generic drugs for their ability to help regrow pancreas cells. Although I don't have visibility into JDRF's decision making, I think it is reasonable to say that since TT-223 did not pan out, JDRF is putting money into other research with similar goals. Unfortunately, that research is not in human trials yet, so I won't be following it.

These are records for Transition Therapeutics's phase-I studies:
http://clinicaltrials.gov/ct2/show/NCT00239148 (type-1)
http://clinicaltrials.gov/ct2/show/NCT00239187 (type-2)

And here is the clinical trial record for their phase-II study (which is type-2 only):
http://clinicaltrials.gov/ct2/show/NCT00853151

I'd like to thank Susan Mohr for some of the information used here.

Alba's Lazotide (previously AT-1001) goes to the Boneyard for type-1 diabetes, but not Celiac Disease

I recently moved Alba Therapeutics's Larazotide (previously known as AT-1001) from my "preparing for clinical trials" section to my "boneyard" for treatments that are no longer under development as cures for type-1 diabetes.

I did this before reading the following Scientific American article:
http://www.scientificamerican.com/article.cfm?id=celiac-disease-insights
That article (written by a founder of Alba Therapeutics) says that the FDA approved human trials for Larazotide for type-1 diabetes. However, I can not find any references at the company's web site that they are planning such a clinical trial, and there is nothing in www.clinicaltrials.gov, either. So therefore it is staying in the boneyard for now.

If you read the article linked above, remember that the author did some of the original research into Larazotide and founded Alba Therapeutics, so is not an unbiased source! In particular, this quote:
Surprisingly, essentially the same trio—an environmental trigger, a genetic susceptibility and a “leaky gut”—seems to underlie other autoimmune disorders as well. This finding raises the possibility that new treatments for CD may also ameliorate other conditions.
This is the author's opinion, however I don't think it is general consensus among researchers. Most researchers believe that autoimmune disorders are built on a foundation of a genetic susceptibility and an environmental trigger. The idea that "leaky gut" underlies autoimmune disorders is a minority opinion. Of course, if Larazotide works the way Alba hopes it will, that might change.

All of the above comments pertain to using Larazotide for type-1 diabetes, not Celiac Disease. The situation for Celiac is much different: Alba is running human trials. There are several listed at www.clinicaltrials.gov, and I think some of them are phase-II. (But I don't follow Celiac closely so am unclear on the details. Also, there appear to be two different drugs called "AT-1001" and "AT1001" so don't get confused.)

Joshua Levy

5 comments:

Bill Ahearn, JDRF said...

Joshua:
Someone forwarded me your posts on type 1 diabetes research. I thought them thoughtful and insightful, and ultimately helpful for people with type 1 in understanding the landscape of research aimed at better treatments and a cure. Keep them coming.
I did want to add some information to your post about JDRF and Transition Therapeutics.
You are correct that JDRF is no longer funding TT’s gastrin- based therapy to regenerate beta cells. However, we stopped funding this research for good reasons, not a lack of results for type 1 diabetes.
JDRF funded TT through an innovative program we began a few years ago called our Industry Discovery and Development Partnership program. We fund small biotech companies with promising ideas for cures and treatments; they need proof-of-concept trials before they can attract large-scale funding from pharma or diabetes companies to carry those targets through the expensive final stages of product development. JDRF acts like an investor, funding early research that will encourage a larger company to step in. If that happens, it’s a win-win for diabetse research and JDRF: a big player takes a promising diabetes drug and moves it through the product pipeline, and we get our funding back and redeploy it for other research.
JDRF stopped funding TT when its proof-of-concept trials encouraged Eli Lilly to create a licensing and collaboration agreement for the gastrin-based product with them. Once Lilly and TT entered into this agreement, there was no longer a funding gap for JDRF to fill, so we were able to direct our funding towards other important research.
Regarding the patients who may benefit from this, the current trials involve type 2 diabetes. However, this is just the initial stage of research. Trials are starting with them because they have existing beta cell mass; later trials are expected to move on to type 1 patients. We’re excited about this research, and are optimistic that beta cell regeneration in general will ultimately help people with type 1.
Thanks again for all you do to keep people with type 1 diabetes informed about research.

Joshua Levy said...

Bill Ahearn is the Vice President, Strategic Communications for JDRF International, so he can speak with an insider's knowledge of JDRF.

I'm very glad to hear that TT-223 may yet be used for type-1. I understand the problem of testing anything that is designed to help beta cells grow in a type-1 diabetic. The autoimmune attack is likely to kill the new growth before you can even measure that it's there. (It is possible that both INGAP and DiaPep227 had this problem.) So testing that it works in type-2 diabetics seems like a reasonable way to move forward. Until we can stop the autoimmune attack. Once we can do that, then suddenly all these beta cell growing treatments will suddenly be very valuable. (That is one cure scenario, anyway.)

biobetter said...

I think it may be premature to bury TT223 for Type 1 diabetes. Transition Therapeutics will announce TT223's results for the P2 type 2 diabetic trial in the 1st qtr of 2010. Then early in the 3rd qtr will come the combo treatment results where Lilly's glp1 + TT223 is tested for type 2. That Lilly has chosen to go after the much larger type 2 market first is econ 101. Besides the greater financial rewards another reason to go after the type 2 disease first is in that group it should be easier to get a therapeutic effect. If the combo treatment works for type 2s than I'd expect a TT223/GLP1 trial for type 1s.

What you may not be aware of is that TT223 has only a 15-30 minute half-life and despite this short time span is given only once a day. Lilly has recently discovered TT223 analogues that have a much longer half life of 4-8 hours. In similar animal studies these gastrin drugs have outperformed TT223. These analogues might be a better alternative to TT223 for the more severe type 1 diabetics.

Anonymous said...

Alba Therapeutics as probably with many other small drug companies was hit by the financial crisis and had to lay off half of its staff. The remaining staff is focused on getting their drug approved for celiac disease. If they get more venture capital or have success with their current research, then it is likely that they will restart research on Type-1 diabetes.

Scott said...

I am curious where JDRF stands on TT-223 given that the trial in type 2 diabetes failed to meet it's primary efficacy endpoint http://goo.gl/Zj1Hr , making us wonder whether these should be moved to a permanent graveyard instead!