JDRF Funding for a Cure 2020

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: 71% of the treatments currently in human trials have been funded by JDRF. (And the number is 80% 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 groups that JDRF has funded, and those JDRF has never funded.  This message is even more important this year, when JDRF's donations have dropped precipitously due to the COVID pandemic.  This year, more than previous years, it is important to continue to fund research aimed at type 1 diabetes.

In Processes To Submit For FDA Approval
Summary: currently there is 1 drug in process of being 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 plans to submit Teplizumab for FDA approval.   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 trials.  Both are funded by JDRF:

• Oral Insulin (Preventative)
• Teplizumab by Provention Bio 

Note: Teplizumab is listed separately here, because it is being tested separately for people with honeymoon type 1 diabetes.

Phase-II Human Trials

Summary: there are 21 trials in phase-II, and 17 of them have been funded by JDRF, while 4 have not. Here are the treatments that have been funded by JDRF:

• AAT (Alpha-1 Antitrypsin) by Kamada 
• ATG and GCSF by Haller at University of Florida (Established) 
• Abatacept by Orban at Joslin Diabetes Center 
• Abatacept by Skyler at University of Miami (Prevention) 
• Aldesleukin (Proleukin) at Addenbrooke’s Hospital, Cambridge, UK 
• Diamyd, Ibuprofen ("Advil"), and Vitamin D by Ludvigsson at Linköping University
• Diamyd, Etanercep, and Vitamin D  by Ludvigsson at Linköping University
• Diamyd and Vitamin D by Larsson at Lund University (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 
• TOL-3021 by Bayhill Therapeutics (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 14 trials in phase-II?, and 8 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
• Golimumab by Greenbaum (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
• Rapamycin Vildagliptin Combo by IRCCS (Established)
• Visbiome by Medical College of Wisconsin

Phase-I Human Trials
Summary: there are 18 trials in phase-I, and 12 of them are funded by JDRF, while 6 are not. Here is the list funded by JDRF:

• AG019 and Teplizumab by ActoGeniX
• Alefacept by TrialNet 
• CGSF by Haller at University of Florida 
• Golimumab by (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)
• Tauroursodeoxycholic Acid (TUDCA) by Goland at Columbia University
• Pro insulin peptide by Dayan at Cardiff University 
• VC-01 by Viacyte (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
• Microvesicles (MVs) and Exosomes by Nassar at Sahel Teaching Hospital 
• ProTrans by NextCell (Established)

Summary of all Trials
56 in total
40 funded by JDRF
So 71% 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
9 of these treatments (16%) are being tested on people with established T1D.
Of these, 6 are funded by JDRF.
So 66% of the trials recruiting people with established T1D are funded by JDRF.

Compared to Last Year
In 2019 there were 56 treatments in clinical trials, in 2020 there are 56 (no change).
In 2019 there was 1 treatment in process of approval to sell, in 2020 there is 1 (no change).
In 2019 there was 2 treatment in Phase-III trials, in 2020 there are 2 (no change).
In 2019 there were 21 treatments in Phase-II trials, in 2020 there are 21 (no change).
In 2019 there were 14 treatments in Phase-II? trials, in 2020 there are 14 (no change).
In 2019 there were 18 treatments in Phase-I trials, in 2020 there are 18 (no change).

The fact that there were no changes at all from last year is discussed below.

A Little Discussion
The big break through from 2019 was that Provention Bio expected to submit Teplizumab for approval in 2020.  Their most recent press release says they are still on that schedule.  They expect to complete their application to the US FDA in the 4th quarter.  

 

This year was unusual in that the total numbers did not change.  That has never happened before.  The studies were not static, a few clinical trials were removed and a few were added, but the overall counts were remarkably consistent from 2019 to 2020.  This might be because the COVID pandemic has slowed down research, but it might also be something else, or just random chance.

 
The money that we all donate is the thing that is going to move more Phase-II studies into Phase-III studies, the Phase-I studies to Phase-II, create more Phase-I studies, and so on.  If you don't like where we are on research, donating money is the way to make it better.  And if you do like where we are, then money is the way to push these things forward into the market.  If you're worried about your money going to non-research, then you can do what I do: fill out the attached form or go to the following website and send it in with your donation: http://thejdca.org/good-giving-landing-page/  (Unfortunately I don't know how to do this for on-line donations.)

Notes on How Trials Are Grouped

 

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. For example, JDRF is not funding the current trials for AAT, but they did fund earlier research into it, which helped it grow into human trials. I also include indirect funding of various kinds.  I also give credit if JDRF funds research 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.

The Difference Between Phase-II and Phase-II? Trials
Phase-II trials are "classic" phase-II trials; they are done after a successful Phase-I trial in type-1 diabetes.  What I call Phase-II? trials are done on known safe treatments, so they don't need Phase-I trials, but have never been tested on type-1 diabetes before.  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.

 

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. Also, I list experiments separately if they use at least one different drug. 
• The ITN (Immune Tolerance Network) has JDRF as a major funder, so I count ITN as indirect JDRF funding. 
• 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 this year was a population based study, so also not included.
• I've removed Dr. Faustman's BCG research from my list of potential cures, because it is no longer aimed at a cure.  For more information read this blog:
  https://cureresearch4type1diabetes.blogspot.com/2018/09/every-year-in-september-or-october-i.html and for even more details
  https://cureresearch4type1diabetes.blogspot.com/2018/07/dr-faustman-publishes-follow-on-bcg.html
• 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.
• Serova's Cell Pouch and DRI's BioHub: These two clinical trials are both testing one piece of infrastructure which might be used later in a cure. They are testing a part of a potential cure. However, in both cases, the clinical trials being run now require immunosuppression for the rest of the patient's life, so I'm not counting them as testing a cure.

This is an update and extension to blog postings that I've made for the previous twelve years:

• https://cureresearch4type1diabetes.blogspot.com/2019/10/jdrf-funding-for-cure-2019.html
  
• https://cureresearch4type1diabetes.blogspot.com/2018/10/jdrf-funding-for-cure-2018.html
• https://cureresearch4type1diabetes.blogspot.com/2017/10/jdrf-funding-for-cure-2017.html
• https://cureresearch4type1diabetes.blogspot.com/2016/10/jdrf-funding-for-cure-2016.html
• https://cureresearch4type1diabetes.blogspot.com/2015/10/jdrf-funding-for-cure-2015.html
• https://cureresearch4type1diabetes.blogspot.com/2014/09/jdrf-funding-for-cure-2014.html
• https://cureresearch4type1diabetes.blogspot.com/2013/10/jdrf-funding-for-cure-2013.html
• https://cureresearch4type1diabetes.blogspot.com/2012/09/jdrf-funding-for-cure-2012.html
• https://cureresearch4type1diabetes.blogspot.com/2011/10/jdrf-funding-research-for-cure-2011.html
• https://cureresearch4type1diabetes.blogspot.com/2010/09/jdrf-funding-research-for-cure-2010.html
• https://cureresearch4type1diabetes.blogspot.com/2009/09/jdrf-funding-research-for-cure.html
• https://cureresearch4type1diabetes.blogspot.com/2008/10/jdrf-funding-of-cure-research-phases-ii.html

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 

https://cureresearch4type1diabetes.blogspot.com 

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 adult 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.

Iscalimab (CFZ533) Starts a Phase-II? Clinical Trial

Iscalimab, also known by its "code name" of CFZ533 started a phase-II? trial last November, and is expected to finish in October 2022.  Although it has not previously been tested on T1D, it has been tested on other diseases.  A total of 11 clinical studies are either completed or currently underway, including several phase-I and phase-II trials. 

Iscalimab is being developed by XOMA and Novartis.  It blocks a specific type of immune cell, called CD40.  The drug has shown some success in clinical trials on Sjögren’s Syndrome, which is an autoimmune disease like T1D.  It has also shown some success in NOD mice (which are commonly used to test potential T1D cures), although there is some controversy about this result.

 

Iscalimab is a monoclonal antibody, which is created by cloning a single cell that attacks the cell you don't want.  You end up with a vast number of identical cells, all of which attack the cell you don't want.  By carefully choosing the starting cell, you can "target" the monoclonal antibody to attack a very specific type of immune cell.  So if a disease is caused by a specific type of bad cell, then using a monoclonal antibody to target that type of cell is a promising treatment. 

This Study

The study is enrolling 102 people into two groups.  Two thirds will get the treatment, while one third will get a placebo and be a blinded control group.  It is expected to finish in Oct-2022.  The trial is open to newly diagnosed (within 2-3 months of diagnosis) children and youth (aged 6-21). 

The primary end points are aimed at safety (adverse events, i.e. "side effects") and effectiveness as a cure (by measuring C-peptides).  There are a bunch of secondary outcomes most of which are focused on how Iscalimab moves through the body, but two are also focused on effectiveness as a cure: another C-peptide measure and a measure of people who go into partial or complete remission.

 

The study is recruiting at three different sites in Belgium (Edegem in Antwerpen, Jette in Brussel, and Montegnee).  You can contact the people running the study here:   +41613241111    novartis.email@novartis.com or clinicaltrial.enquiries@novartis.com

 

Discussion

One thing unique about this study is that the drug will be given in two different ways.  The first dose will be given "intravenously", meaning into the vein.  This generally must be done under the supervision of a medical professional.   However, after the first dose, all other doses will be given "subcutaneously", meaning under the skin.  This is how insulin is injected, and can be done by anyone at home.

This drug has already completed 5 studies in other diseases, so its safety is well understood, which is why it has skipped a phase-I trial in people with T1D and jumped directly to a phase-II study.   That is why I call this study a phase-II? study.  From a safety point of view it is a phase-II study, but from an effectiveness point of view, it is a phase-I study.

 

Iscalimab is the second T1D drug that XOMA has gotten into clinical trials.  Over 10 years ago, they started a phase-II trial into Gevokizumab (Xoma 052).  That was also a monoclonal antibody, but it targeted a different part of the immune system (called IL-1).  It was unsuccessful.

Clinical Trial: https://www.clinicaltrials.gov/ct2/show/NCT04129528

Also registered in the EU: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-004553-25/BE

NOD mouse results: https://link.springer.com/article/10.1007%2Fs00125-014-3342-5 

Controversy in CD40 NOD mice research: https://link.springer.com/article/10.1007/s00125-019-4893-2

Genetic Result for CD40: https://academic.oup.com/jes/article/4/Supplement_1/SAT-669/5833379

 

News (not T1D):  

• https://www.novartis.com/news/media-releases/novartis-presents-first-its-kind-histology-data-iscalimab-cfz533-suggesting-extended-survival-transplanted-organs-may-be-possible
• https://atcmeetingabstracts.com/abstract/cfz533-a-new-anti-cd40-mab-demonstrates-comparable-efficacy-and-better-renal-function-versus-tacrolimus-in-de-novo-cni-free-kidney-transplantation
  
• https://pubmed.ncbi.nlm.nih.gov/31512728/
• https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(19)30135-3/fulltext

 

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 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.