Sunday, October 16, 2022

JDRF Funding for a Cure 2022

In the US, we are in the "Walking Season" when JDRF (Juvenile Diabetes Research Foundation) asks us to walk to raise money for a cure for type-1 diabetes. So I'd like to do my part, by reminding you all of how important JDRF is to the human trials of potential cures for T1D, which I track.

Let me give you the punch line up front: 65% of the treatments currently in human trials have been funded by JDRF. (And the number is 78% for the later phase trials!) This is a strong impact; one that any non-profit should be proud of.  Below is a list of all the treatments, grouped by phase, and separated into trials that JDRF has funded, and those JDRF has never funded.  
I've made two big changes to how I track treatments this year.  
  • In the past, I counted each combination of treatments separately.  For example,  Diamyd, Etanercep, and Vitamin D was considered one possible cure and Diamyd alone was a separate possible cure, and Diamyd and Vitamin D was a third.  This year, I'm changing my methodology to group all of these possible cures together as one, since they are all really based on Diamyd.
  • In the past, I counted a possible cure separately if it was tested in different phases of type-1 diabetes.  For example, TOL-3021 was being tested on honeymooners, but also in people with established T1D, so it got counted twice.  This year, I'm no longer doing that.  Another example is Teplizumab.  It is in the approval process for at-risk people, but in phase-III trials for honeymooners, so it is listed in both phases but only counted once.

The List, Divided by Phases
Below is the list of all treatments, divided into five phases: In Process (of FDA Approval), Phase-III, Phase-II, Phase-II?, and Phase-I.  Phase-II trials are "classic" phase-II trials, which are done after a Phase-I trial.  What I call Phase-II? trials are done on treatments which never went through phase-I trials on people with T1D.  They've been shown safe in other diseases, so have skipped phase-I trials on people with T1D.  These Phase-II? trials might be Phase-II from the point of view of size and safety, but they are Phase-I in terms of effectiveness, so I'm putting them in their own category. 

In Process of FDA Approval
Summary: currently there is 1 drug which has been submitted to the US FDA for approval for sale, and it was funded by JDRF.
  • Teplizumab by Provention Bio (At Risk)
In the forth quarter of 2020, Provention Bio submitted Teplizumab for FDA approval.  Unfortunately, there have been some delays, but there is hope of an FDA decision in November  2022.  This application will cover people who are "At Risk" (as described below) for T1D, and the aim will be to delay the onset of T1D by 2-3 years.

Phase-III Human Trials
Summary: currently there are 2 treatments in a phase-III clinical trial.  Both are funded by JDRF:
  • Oral Insulin (Preventative)
  • Teplizumab by Provention Bio
Phase-II Human Trials
Summary: there are 16 trials in phase-II, and 12 of them have been funded by JDRF, while 4 have not. Here are the treatments that have been funded by JDRF:
  • ATG and GCSF by Haller at University of Florida (Established) 
  • Abatacept in honeymooners and as a prevention by Orban at Joslin Diabetes Center and Skyler at University of Miami (Prevention) 
  • Aldesleukin (Proleukin) at Addenbrooke’s Hospital, Cambridge, UK 
  • Diamyd in several combinations by Ludvigsson at Linköping University and Larsson at Lund University (Honeymoon and Prevention)
  • Gleevec by Gitelman at UCSF 
  • Gluten Free Diet: Three Studies  (Preventative)
  • Stem Cell Educator by Zhao (Established) 
  • Tocilizumab by Greenbaum/Buckner at Benaroya Research Institute 
  • TOL-3021 by Bayhill Therapeutics (Honeymoon and Established)   
  • Umbilical Cord Blood Infusion by Haller at University of Florida 
  • Ustekinumab by University of British Columbia
  • Verapamil by Shalev/Ovalle at University of Alabama at Birmingham
Not funded by JDRF:
  • ATG and autotransplant by several research groups: Burt, Snarski, and Li 
  • Dual Stem Cell by Tan at Fuzhou General Hospital 
  • Stem Cells of Arabia (Established)
  • Vitamin D by Stephens at Nationwide Children's Hospital (Prevention)
Phase-II? Human Trials
Summary: there are 13 trials in phase-II?, and 7 of them have been funded by JDRF, while 6 have not. Here are the treatments that have been funded by JDRF:
  • Alpha Difluoromethylornithine (DFMO) by DiMeglio
  • GABA by Diamyd
  • Golimumab by Janssen (Honeymoon and Established)
  • Hydroxychloroquine by Greenbaum (At Risk)
  • Intranasal Insulin by Harrison at Melbourne Health (Prevention)
  • Iscalimab (CFZ533) by Novartis
  • Rituximab by Pescovitz at Indiana University
Not funded by JDRF:
  • Azithromycin by Forsander
  • Ladarixin by Emanuele Bosi of Dompé Farmaceutici
  • Liraglutid (At Risk)
  • NNC0114-0006 and Liraglutide by Novo-Norsk (Established)
  • Rapamycin Vildagliptin Combo by IRCCS (Established)
  • Visbiome by Medical College of Wisconsin
Phase-I Human Trials
Summary: there are 22 trials in phase-I, and 15 of them are funded by JDRF, while 7 are not. Here is the list funded by JDRF:
  • AG019 and Teplizumab by ActoGeniX
  • DIMID1 (Faecal Microbiota Transplantation) at AMC Hospital 
  • CGSF by Haller at University of Florida 
  • Golimumab (At Risk)
  • MER3101 by Mercia (previously IBC-VS01 by Orban)
  • MonoPepT1De by Cardiff University
  • Mozobil by University of Alberta (Established)
  • MultiPepT1De (Multi Peptide Vaccine) by Powrie at King’s College London
  • Nasal insulin by Harrison at Melbourne Health (Prevention)
  • PRV-101 (Coxsackie B Vaccine) by Provention Bio (Prevention)
  • Tauroursodeoxycholic Acid (TUDCA) by Goland at Columbia University
  • TOPPLE T1D by Novo Nordisk (Established)
  • Pro insulin peptide by Dayan at Cardiff University 
  • VC-01 by Viacyte (Established)
  • VCTX210A by Viacyte/CRISPR (Established)
Not funded by JDRF:
  • AVT001 by Avotres
  • Baby Teeth Stem Cells by CAR-T Biotechnology 
  • Gluten Free Diet by Carlsson at Lund University
  • Mesenchymal Stromal Cell by Carlsson at Uppsala University
  • NN1845 (Glucose Sensitive Insulin) by Novo Nordisk
  • PIpepTolDC at City of Hope Medical Center
  • ProTrans by NextCell (Established)
Summary of all Trials
52 in total
34 funded by JDRF
So 65% of the human trials currently underway are funded (either directly or indirectly) by JDRF. Everyone who donates to JDRF should be proud of this huge impact; and everyone who works for JDRF or volunteers for it, should be doubly proud.

Just Looking at Trials on Established Type-1 Diabetics
12 of these treatments (23%) are being tested on people with established T1D.
Of these, 8 are funded by JDRF.
So 66% of the trials recruiting people with established T1D are funded by JDRF.

I'm not comparing these numbers to the 2020 numbers because I've changed the way I count potential cures, so the numbers are not equivalent.   However, I did do a quick comparison applying the older methodology to this year's data, and there was little change: 4 more phase-I trials, and 1 less phase-II trial. 

A Little Discussion
The money that we donate does many things:
  1. It finances more clinical trials (especially early clinical trials).
  2. It finances making clinical trials (especially early clinical trials) larger and better designed.
  3. It helps push possible cures to the next level of trial.  It finances moving phase-I trials to phase-II, and phase-II to phase III.
I like to say that there are two reasons for donating money for research into T1D.  People who like the research being done should donate money to move it forward, faster.  People who don't like the research being done should donate money to start up different research which (presumably) they will like more.  So no matter which group you are in, you should donate.  😀
Trial Populations
The list above uses the following marks to show the nature of the treatments, and if one treatment is being tested in different populations, then it will be listed more than once.
Honeymoon: Most trials are done on people within the first year of diagnosis.  All the studies listed above which are not Established, At Risk, or Prevention are in this Honeymoon category.
Established: One or more trials are open to people who have had type-1 diabetes for over a year. 
At Risk: One or more trials are open to people who have 2 or more autoantibodies, but have not yet started showing symptoms of type-1 diabetes.
Prevention: This treatment is aimed at preventing type-1 diabetes, not curing it.
If a trial is not marked, then it is for people in the honeymoon (first year) of T1D.

I give an organization credit for funding a treatment if they funded it at any point in development; I don't limit it to the current trial.  
I also give credit if JDRF funds research indirectly, through another organization.  For example, JDRF funds both nPOD and Immune Tolerance Network and so I give JDRF credit for clinical trials based on their work.
How I Count Trials for This Comparison
  • I mark the start of a research trial when the researchers start recruiting patients (and if there is any uncertainty, when the first patient is dosed). Some researchers talk about starting a trial when they submit the paper work, which is usually months earlier. 
  • For trials which use combinations of two or more different treatments, I give funding credit, if the organization in the past funded any component of a combination treatment, or if they are funding the current combined treatment.
  • I have made no attempt to find out how much funding different organizations gave to different research. This would be next to impossible for long research programs, anyway. 
  • Funding of research is not my primary interest, so I don't spend a lot of time tracking down details in this area. I might be wrong on details. 
Some Specific Notes:
  • I only include intervention studies here, because those are the only type of study that the FDA will accept for the eventual approval of a new treatment.  
    • The PreventT1D study (Vitamin D and Omega-3s) is a "field study" so not included.
    • A Rotavirus Vaccine study which was published a few years ago was a population based study, so also not included.
  • Oral Insulin: This trial was a phase-III trial, meaning that it was large and designed to provide enough information so that, if successful, the treatment could be widely used. However, as it turned out, only part was successful, and that part was phase-II sized, so I don't think we will see widespread use based on this trial alone. You can think of this as a phase-III trial with phase-II results.
This is an update and extension to blog postings that I've made for the previous twelve years:
Please remember that my blog (and therefore this posting) covers research aimed at curing or preventing type-1 diabetes that is currently being tested in humans. There is a lot more research going on than is counted here.

Please think of this posting as being my personal "thank you" note to all the JDRF staff, volunteers, and everyone who donates money to research a cure for type-1 diabetes:
Thank You!

Finally, if you see any mistakes or oversights in this posting, please tell me! There is a lot of information packed into this small posting, and I've made mistakes in the past. 

Joshua Levy
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA 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.