This blog posting reports on the results of Avotres recent phase-I clinical trial into AVT001 and the company's future plans for testing. I reported on the start of this trial here:
AVT001 is an "autologous dendritic cell therapy" meaning that a person's own dendritic immune cells are taken out, processed in some way, and then put back. Dendritic cells can be thought of as the immune systems "sensors". They detect foreign invaders and then communicate that knowledge to other types of immune cells (especially T cells).
This trial flows out of some work done at Columbia University. Researchers there found a defect in a specific type of immune cell called a HLA-E–restricted CD8+ T cells. They believe that this defect leads to the immune system attacking the beta cells in the pancreas and causing type-1 diabetes. The basic technique being tested here is to take out dendritic cells from the patient and treat those cells so that when they are put back into the patient, they (in turn) fix the defect in the HLA-E–restricted CD8+ T cells which leads to type-1 diabetes.
This Study and Its Results
This study involved 25 people, 16 were in the treatment group and 9 in a control group. They were 16 years old or older, and in their honeymoon phase after diagnosis of T1D. There were primary end points for safety and a secondary end point for C-peptides. For me, the key results are below.
The table below covers a year, from left to right on the bottom, and the amount of C-peptides a person generated, from zero up, on the left side. A flat line shows success. The body continues generating C-peptides. For the first 150 days for the treated group, C-peptide numbers do not drop at all. This is the flat purple line. After that they did drop at about the same rate as untreated people. This is the purple line dropping down. You can notice that the purple line and the dotted orange line (the untreated group) drop at about the same rate. The difference is that the untreated group started immeadiately, but the treated group stayed constant for at least 150 days. Since the treatment group was given three infusions, 30 days apart, the treatment last 90 days (infusions were on days 1, 30 and 60). The treatment prevented beta cell loss for at least 90 additional days. Safety and side effect data showed that there were no safety issues.
That's hopeful news in terms of prevention. It suggests that giving this drug before the honeymoon phase might prevent T1D or at least delay it. Of course, a study giving this treatment to pre-honeymooners would be needed to see if this actually happened. Such a test would compare pre-honeymooners who got the treatment to pre-honeymooners who did not, and see how many of each group progressed to the honeymoon phase of type-1 diabetes. If enough people are enrolled, and they are followed for long enough, such as trial could be run. My memory is that such trials have been run lasting 2 and 5 years, and enrolling from 1 to 3 hundred people, so it is reasonable to do.
Also, it is important to remember that this treatment involves removing white blood cells from a person's blood, treating the cells in a lab, and then intravenously infusing them back into the person with T1D. So this is two clinic visits per treatment.
Journal Article: https://evidence.nejm.org/doi/abs/10.1056/EVIDoa2300238
Clinical Trial Registry: https://clinicaltrials.gov/study/NCT03895996
What Next?
From the point of view of Avotres, this was a clearly successfully phase-I/II and so are in discussions with the FDA to set up a phase-III clinical trial as the next step. There is no advantage in speculating as to what the FDA will do. The only thing that makes sense to do is wait a few months (or a year) and see what actually happens.
From my point of view, this was a successful phase-I study, which showed that AVT001 might work as a T1D prevention. If given to people before the honeymoon, it might delay or even prevent the onset of T1D. Therefore, Avotres could turn this into a prevention/delay treatment (like Tzield®) by running three more studies (one one phase-II study and two phase-III studies as a minimum) to get approval.
In addition Avotres could try to apply AVT001 to treatment of established T1D in a different set of clinical trials, and see where that led.
For background, the FDA generally requires one phase-I study, one phase-II study, and two phase-III studies as a minimum for approval, although there are occasional exceptions.
Company website: https://www.avotres.com/ and https://www.avotres.com/companyoverview
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 BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!
