DiaVacs Starts a Phase-II Trial of Dendritic Cells (DV-0100)
DiaVacs is a newly created company with a goal of further developing the Dendritic Cell research done in Dr. Trucco's lab. You can read my previous blog posting on this research here:
http://cureresearch4type1diabetes.blogspot.com/2011/11/results-from-truccos-phase-i-dendritic.html
The idea behind this research is to remove dendritic cells from a person, grow them out, and then put them back in. The hope is that they will then regulate the immune system and cut down on the autoimmune attack. Dendritic cells are part of the immune system which find foreign cells and "present" them to T-cells (another part of the immune system) so that they know what to attack. You can read more about them here:
http://en.wikipedia.org/wiki/Dendritic_cells The goal of this therapy is to interrupt the immune system's internal communications so as to stop the immune attack on beta cells, without stopping immune attack on foreign cells.
The goal is to enroll 90 people, eventually. The first 10 will need to be adults, and then the hope is that the safety record from those first patients will be used to get the FDA to approve children. Since this is a honeymoon trial (within 6 months of diagnosis), limiting recruiting to adults will slow everything down, but the FDA will not approve a trial on children without some safety data from adults, if they can possibly avoid it.
Treatment is expected to last 3 months, and then patients will be followed for another year. Primary goal is safety, secondary goal is C-peptide production (as a stand-in for insulin production) 12 months after treatment. C-peptides are measured because they are created naturally when insulin is generated by the body. So they are a measure of natural insulin production. Insulin measurements can't be used, because there is no way to tell if the insulin was injected or created naturally. So all modern research measures C-peptide to determine insulin production.
A Little Discussion
When I heard this group was doing a phase-II trial, I was a little surprised. If you look at my summary of their phase-I trial, I did not see a clear success in their Phase-I results. There were some results that the researchers viewed positively, but there was no improvement to insulin generation (for example). However, that first study was done on established type-1 diabetics. My understanding is that they expect this treatment to stop the immune attack, but not automatically regrow beta cells, so it should be much more effective in the honeymoon phase, because there are still some beta cells at that time.
Put another way, the researchers did not expect this treatment -- by itself -- to cure established type-1 diabetes. They did expect it to have some impact on the immune system, and think that it did, and think that the impact of these changes will be seen when used on honeymooners.
In some ways, this treatment is similar to the "Polyclonal Tregs" treatment, which is in phase-I trials for honeymooners. One difference is that different immunology cells are being amplified (a specific type of T-reg cell vs. a dendric cell).
News:
http://www.news-medical.net/news/20140106/FDA-grants-orphan-drug-designation-for-DiaVacs-type-1-diabetes-mellitus-therapy.aspx
http://www.post-gazette.com/news/health/2014/02/10/Type-1-Diabetes-A-treatment-s-in-sight-but-where-s-the-funding
Clinical Trial Record:
http://www.clinicaltrials.gov/ct2/show/NCT01947569
Corporate Site:
http://www.diavacs.com/
Facebook:
https://www.facebook.com/DiavacsTheCureForJuvenileDiabetes
DiaPep277 Starts an Extension to Their Phase-III DIA-AID2 Study
In the past I have thought that DiaPep277 might result in a cure, but I no longer think that is likely, but it still maybe be used as a treatment or a honeymoon extender. In case people are still interested, you can read my previous blogging here:
http://cureresearch4type1diabetes.blogspot.com/search/label/DiaPep%20277
The recent news, is that they have started treating their first patient in an extension to their phase-III clinical trial. That means the main part of the phase-III study is done, and this is the second such trial. So they have the option of starting the process of getting marketing approval (so they could actually sell it, and we could buy it). I don't think any truly new treatment for type-1 diabetes has ever entered the FDA's marketing approval phase before. (Not counting different versions of insulin.)
Opinion
It will be interesting to see if these guys try to get it approved, and if so, will the FDA approve it, and will insurers pay for it? My take is that the impact of the treatment is pretty small. The safety profile is good, however, so the FDA could approve it as a small impact, small risk treatment. But they could decide the impact is so small that it should not be approved. Even if the FDA approves it, some insurance companies might not pay for it, arguing that it does not give a large enough benefit, or does not give a cost effective benefit.
Here are some recent news stories:
http://online.wsj.com/article/PR-CO-20140112-900596.html
http://www.pharmabiz.com/NewsDetails.aspx?aid=79410&sid=2
Abatacept
Abatacept is a treatment that prevents T-cells from becoming activated. Presumably, for type-1 diabetes, it works by blocking the "bad" killer T-cells from activating. ("Bad" killer T-cells are those which target the body's own beta cells rather than the foriegn invaders they are supposed to target). This drug is already approved for use in rheumatoid arthritis when other treatments have failed, and is marketed as Orencia. It regulates (or modulates) T-cells, rather than depleting them, so the hope is that it will have fewer side effects than other immunosuppressives.
This was a honeymoon study. It was a placebo controlled, double blind trial with 112 patients. About 2/3s (77 people) got the treatment and 1/3 (35 people) did not. The treatment consists of three infusions the first month, and one a month thereafter for two years. C-peptide production in response to a meal was measured after two years. Those results were discussed in a previous blog:
http://cureresearch4type1diabetes.blogspot.com/2011/09/results-from-phase-ii-trial-of.html
Now, the researchers have published a follow-on paper, which contains data for a C-peptide production a year later. So this is one year after the last dose of Abatacept, and three years after diagnosis (approximately).
Results
People treated with Abatacept continued to generate about 50% more of their own insulin, than those not treated. The amount of insulin generated years after diagnosis is pretty small, so the actual difference is half of a tiny number. One way to view these results was that Abatacept delayed the "end of insulin generation" by 9.5 months. Someone who got the drug generated the same amount of insulin 36 months after diagnosis as someone who did not get the drug generated 27 months after diagnosis.
Discussion
My view of this drug is very similar to my view of Rituximab in a blog posting last month. (Which makes sense, since the results were similar.) By itself, it's not a big step towards a cure. I used to hope that by combining drugs or changing doses, researchers would take so-so results like these, and create a cure or a preventative. However, I have yet to see many clinical trials where these sorts of drugs are combined, or doses changed significantly, or any other way of improving on these results. And these results, as reported here, are not going to lead to a cure.
Abstract:
http://care.diabetesjournals.org/content/early/2013/11/22/dc13-0604.abstract?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.
