Wednesday, January 8, 2014

Possible Cures for Type-1 in the News (early January)


This posting covers two news items and discussion to go with each.  I'm about 4 months behind on blogging about current events that might lead to a cure or prevention of type-1 diabetes.  Even after this posting, I'll still be several months behind.  I hope to catch up by end of January.

As you read these summaries, remember that C-peptide is generated when your body makes it's own insulin, so more C-peptide means your body is generating more of it's own insulin.

Results from Alefacept in a Phase-II Trial ("T1DAL")

Alefacept is a drug that has been used to treat the skin condition, psoriasis.  Psoriasis is generally considered to be an autoimmune disease, similar to type-1 diabetes, but with the body attacking it's own skin cells, rather than it's own beta cells.  So trying a drug already approved for Psoriasis on type-1 diabetes seemed like a reasonable thing to do, and these researchers did it.  You can read my previous blogging here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Alefacept

This was a honeymoon trial.  33 people got the drug and were compared to 16 who did not.  The treated group got a dose a week for 12 weeks, then a 12 week break, and then weekly doses for 12 more weeks.  They will be followed for 2 years, but these results only cover the first year.

Results

There were six results:
1. A two hour after eating C-peptide test: Treated generated about 0.130 nmol/L more than untreated, but this was not statistically significant.  However, all the rest of the results were statistically significant:
2. A four hour after eating C-peptide test: Treated generated about 0.171 nmol/L more than untreated.
3. Daily amount of insulin used: Treated people used about 25% less insulin.
4. Number of low BG events: Treated people had 10 such events vs. 17 in untreated.
5. No difference in A1c numbers between treated and untreated groups.
6. No serious adverse effects occurred.

Discussion

This is a good news / bad news kind of study.  I'll give you the bad news first:
* Because the first measure was the primary end point, this trial failed it's primary end point.  The others were secondary end points, some of which were successful.

Good news second:
* In for both of the C-peptide numbers, the treated group actually went up (a tiny amount) in the year after diagnosis, while the untreated group went down. So it is possible, that using this drug earlier in the process will preserve more beta cell function.
* Using 25% less insulin (with no difference in A1c numbers), and having half the low BG events both seem promising to me as well.

But the important thing to remember about this study, is that Alefacept is no longer on the market.  When this study started, it was being sold as an anti-Psoriasis drug.  However, the manufacturer withdrew it from the market while this study was running.  (The study was a little smaller than planned, because of that.)  The drug was not subject to any kind of recall prior to the withdrawal.

Because the drug is no longer on the market, I'm not sure if this research will move forward or not.

News: http://medicalxpress.com/news/2013-09-psoriasis-drug-results-diabetes.html
Abstract: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70111-6/abstract
Web page: http://www.immunetolerance.org/news/2011/04/itn-announces-enrollment-first-participant-t1dal-trial-people-recently-diagnosed-type-1
Recruiting web site: http://www.t1dal.org/
Clinical Trial: http://www.clinicaltrials.gov/ct2/show/study/NCT00965458
Official Notice of Withdrawal: http://www.amevive.com/Patient%20letter.pdf


Results from Extended AAT (Glassia) Phase-I/II Trial

There are two pieces of news on AAT.  One is the results of an extension to their phase-I clinical trial, the other is informal news of a specific case study.  In this blog posting, I'm only covering the phase-I trial.  I'm gathering more information on the case study, and will present that in a future blog posting (probably at the end of January).

AAT is an anti-inflammatory chemical which the body makes naturally, and which is already FDA approved for people who have a rare condition where they don't make enough of it on their own.  There are several clinical studies going on, which use AAT.  In October, one of those studies released data on 20 people who were followed for 20 months after diagnosis.  There was no control group for this phase-I study. You can read more about AAT here:
http://cureresearch4type1diabetes.blogspot.com/p/drugs-and-treatments-in-clinical-trials.html
Results

Three results were reported:
* 60% of the patients where generating more than 0.2 nmol/L of C-peptide.
* 75% of the patients had an A1c of 7.5 or lower.
* No safety issues were found.

Because there was no control group, I can not directly compare these results to an untreated group of people.  However, my understanding is that both of these numbers are better than expected without treatment.  So this looks like good news, although not cure-type news, and without a comparison group, it's hard to tell.

Next Steps

Kamada is planning a phase-II/III study with 190 people.  The plan is for a double-blind, placebo-controlled, multicenter study on honeymoon type-1 diabetics.   The study will follow people for two-years measuring C-peptide parameters, HbA1C levels, hypoglycemic events, insulin daily dose, safety/tolerability, etc.  They will start in Israel, and expand elsewhere later.

Press Release: http://www.kamada.com/press_item.php?ID=73
The new study: http://clinicaltrials.gov/ct2/show/NCT02005848

Factoid: Type-1 Prevalence in USA Might be 1 in 500

Ten years ago, when my daughter was diagnosed, we were told that about 1 in 250 or 300 people had type-1 diabetes.  Over the years I've seen those numbers repeated many times for the US population, and they seem to fit in with what we see in schools.  Many with a few hundred students have zero or one type-1 diabetics, and those with several hundred often have one or two.   So it all makes sense.

However, a study recently published suggests that the actual number might be just under 1 in 500.  You can read the details at the link below, but they found a prevalence of 1.93 per 1000 in kids 20 and under:

Abstract: http://care.diabetesjournals.org/content/early/2013/09/11/dc13-1838.abstract.html?papetoc


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com 
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Tidepool news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

2 comments:

Valentin Andrei said...

Hi Joshua,

Happy New Year!

Great article, as usual, but it’s so frustrating to see things like this, when a drug who demonstrate that can be used as a possible cure, it’s retired from the market. This reminds me “Pancreate”, the CureDM’s product, bought by Sanofi in 2009…and no news since then…
Could you advise me what is the way to measure the C-Peptid? First of all, I see no doctor to recommend this due to the reason “regardless of its current value, it will decrease day by day…”. If you still insist, it’s a must to eat nothing for at least 12h. I know that the C-Peptid is generated when te pancreas is generating insulin, right? But we also now that the pancreas in producing continuously, but only when it’s needed, and I think that after 12-13h without any food, what insulin will be generating?
In that study I observed that those researchers measure the C-Peptid after two and also after four hours after eating. I saw this method only in clinical trials, but not in the “real life”.
Thank you!

Josh Eisenfeld said...

Hey Joshua,

I'm a documentary filmmaker following a trial for a preventative cure of type 1. I would like to talk to you more about the trials you have been reporting on. Please feel free to email me at josh@4twelvepictures.com