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

Discussion in 'Research' started by joshualevy, Feb 22, 2014.

  1. joshualevy

    joshualevy Approved members

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    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/20...DiaVacs-type-1-diabetes-mellitus-therapy.aspx
    http://www.post-gazette.com/news/he...-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.
     
  2. sszyszkiewicz

    sszyszkiewicz Approved members

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    Thank you Joshua!
     
  3. katerinas

    katerinas Approved members

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    Is it me or are the results getting gloomier? I remember 2-3 years ago reading the possible cures (thanks Joshua!) and having something to look forward to. I haven't felt this way at all the last year or so.
     
  4. sszyszkiewicz

    sszyszkiewicz Approved members

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    I am new....and have only been watching 3 months. I had the luxury of reading old articles and seeing how things actually panned out in the same day. It was like being able to watch an entire season of your favorite sitcom without having to wait an entire year because it was on Netflix and you could simply press "Watch Next Episode".

    This is just me, and I am no researcher or in the medical profession, but after spending literally hundreds of hours reading whatever I could about cures/potential cures/ongoing research etc....to solve this problem wholistically there are going to be three breakthroughs that will have to be combined. A way to modulate the immmune system. A way to transplant beta cells back into those afflicted with the disease, and finally those cells will have to somehow come from the person who needs the transplant.

    So you can close your eyes and imagine going to the hospital with your DC where you get something like the "Stem Cell educator" treatment and simultaneously get some skin cells scraped so they can turn those cells into beta cells in the lab, and then in a couple of months, after the immune system has been modulated, you are transplanted with a Biohub or Cell pouch or some other encapsulation technology that contains your beta cells. You may have to do that every 5 years initially, but they will get better at it. There seems to be a lot of realization that the encapsulated cells need a good source of oxygen.

    The above represents the impressions I get by looking at the history that was written before I got here,and I could read about it all at once (mostly due to Joshua's blog...and then the many places that lead to)

    In the mean time I will keep my DC as healthy as possible by taking advanatge of whatever technology that helps us get through the daily grind. I will advocate for research organizations that are dealing with this at a level I cannot begin to understand. But when I get depressed....I close my eyes and imagine that car ride to the TREATMENT center.
     
    Last edited: Feb 24, 2014
  5. Deal

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    The more time that passes the more realistically you look at the timeline between today and the day your child no longer has to test daily, count carbs, or wear technology.

    I like your vision of a practical cure. It might be shortened somewhat if the cell education component can be skipped. That's a very complex outcome to think we can stop our immune system from doing just one action. I don't see that happening. I also think the process of using the subjects cells to create individualized beta cells will be very expensive and not very scalable.

    The implanted pouch however may be able to shield it's internal cells from attack all while allowing blood/oxygen supply to it. They also may be able to use generic glucose responsive insulin producing beta cells based on Pig cells within that pouch as well. That is where my hope lies and it is an area of active research.

    I hate to estimate time lines but my belief is we will all be encouraged and talking about the actual solution on these boards 10 years before any of our kids receive it. How long until that 10 year clock starts is real hard to guess. People have been predicting it any day now for over 30 years.
     
  6. joshualevy

    joshualevy Approved members

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    I think that my coverage might be getting gloomier. Years ago, if researchers talked about a treatment being a potential cure, then I would treat it like a potential cure. But over the last year, I've stopped doing that. If the results don't look like a cure to me, I consider it a treatment, not a cure, no matter what the researchers think of it. (No matter how optimistic they are.)

    Similarly, if a treatment had a very small effect in phase-I or phase-II trials, I was still optimistic about it, and my reporting reflected that optimism. That's because I was hoping they would do better in the next phase of trials. Or, they would find a way to combine it with another treatment or change the dose or something to make it much more effective. But again, in the last year, I've come to the conclusion that it rarely happens that way. If the results are so-so in phase-II, they are not going to be great in phase-III, and so on. So, again, my reporting is less optimistic than it used to be.

    Joshua Levy
     
  7. katerinas

    katerinas Approved members

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    I have also become more sceptical over the years. the only thing that I am still excited about is the CGM technology.
     

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