Breakthrough T1D (formerly JDRF) Funding for a Cure 2024

Normally, sometime in October, I write a summary of all the clinical trials funded by JDRF.   However, this year I didn't, which was a mistake.  But late is better than never, so in this post I summarize the clinical trails that Breakthrough T1D (formerly JDRF) is funding as of October 1st, 2024.

I hope to remind everyone of how important Breakthrough T1D 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 Breakthrough T1D, and this goes to 77% for the Phase-III and Phase-II studies!  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 Breakthrough T1D has funded, and those Breakthrough T1D has never funded.  

 

The List, Divided by Phases

Below is the list of all treatments, divided into six phases: FDA Approved, In Process of Approval, Phase-III, Phase-II, Phase-IIΔ, and Phase-I.  Phase-II trials are "classic" phase-II trials, which are done after a Phase-I trial.  What I call Phase-IIΔ trials test treatments which never went through phase-I trials on people with T1D.  (I used to call those Phase-II? but I think using punctuation that way is confusing, so I'm using a delta instead: Phase-IIΔ.)  They've been shown safe in other diseases, so have skipped phase-I trials on people with T1D.  These Phase-IIΔ 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.

For T1D research, phase-I studies are usually about 10 people and test for both safety and efficiency.   In other diseases, phase-I trials are sometimes only done on healthy people, or only test for safety issues, but this is not the way T1D research is usually done.  Over 90% of phase-I studies are done on people with T1D, and over 90% test for both safety and effectiveness.

Phase-II trials are about 100 people, and phase-III about 300. After two successful phase-III trials, the FDA considers approval for general use.  These two studies can be run at the same time, and are often identical.  Occasionally, only one phase-III trial is required for approval. 

Approved or In Process of FDA Approval

In 2024, nothing was approved and nothing is in process of approval.

Phase-III Human Trials

Summary: currently there are 3 treatments in phase-III clinical trials.  2 are funded by JDRF:

• Diamyd by Diamyd 
• Oral Insulin (Preventative)
  

Not funded by JDRF:

• Ladarixin by Dompé
  

Phase-II Human Trials

Summary: there are 19 trials in phase-II, and 15 of them have been funded by Breakthrough T1D, while 4 have not. Here are the treatments that have been funded by Breakthrough T1D:

• 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) 
• Difluoromethylornithine (DFMO) by Panbela
  
• Gleevec by Gitelman at UCSF 
• Gluten Free Diet: Three Studies  (Preventative)
• Rituximab and Abatacept by TrialNet
• Stem Cell Educator by Zhao (Established) 
• Tauroursodeoxycholic Acid (TUDCA) 
• 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-IIΔ Human Trials
Summary: there are 19 trials in phase-IIΔ, and 10 of them have been funded by Breakthrough T1D, while 9 have not. Here are the treatments that have been funded by Breakthrough T1D:

• Alpha Difluoromethylornithine (DFMO) by DiMeglio
• Baricitinib by St Vincent's Institute of Medical Research
• 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
  
• Influenza Vaccination at Aarhus University Hospital
• Pleconaril and Ribavirin by Oslo University Hospital
• Siplizumab by NIH and ITB-Med LLC

Not funded by JDRF:

• Abrocitinib or Ritlecitinib by NIH/Pfizer
• Azithromycin by Forsander
• BMF-219 by Biomea Fusion (Established)
• Fenofibrate at Warsaw Medical University
• Ixekizumab/Taltz by Vastra Gotaland Region
  
• 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 21 trials in phase-I, and 13 of them are funded by Breakthrough T1D, while 8 are not. Here is the list funded by Breakthrough T1D:

• AG019 and Teplizumab by ActoGeniX
• DIMID1 (Faecal Microbiota Transplantation) at AMC Hospital 
  
• Diamyd by Diamyd (At Risk)
• CGSF by Haller at University of Florida 
• Golimumab (At Risk)
• MER3101 by Mercia (previously IBC-VS01 by Orban)
• Mozobil by University of Alberta (Established)
• PRV-101 (Coxsackie B Vaccine) by Provention Bio (Prevention)
• Semaglutide by Dandona at University of Buffalo
  
• TOPPLE T1D by Novo Nordisk (Established)
• VC-01 by Viacyte (Established)
• VCTX210A by Viacyte/CRISPR (Established)
  
• VX-264 by Vertex (Established)

Not funded by JDRF:

• AVT001 by Avotres
  
• Baby Teeth Stem Cells by CAR-T Biotechnology
• Extracorporeal Photopheresis by ADSCC
  
• Gluten Free Diet by Carlsson at Lund University
• NN1845 (Glucose Sensitive Insulin) by Novo Nordisk
• OPT101 by Op-T (Established)
• PIpepTolDC at City of Hope Medical Center
• ProTrans by NextCell (Established)

Summary of all Trials
62 in total
40 funded by JDRF
So 65% of the human trials currently underway are funded (either directly or indirectly) by JDRF. Everyone who donates to Breakthrough T1D should be proud of this huge impact; and everyone who works for Breakthrough T1D or volunteers for it, should be doubly proud.

Just Looking at Trials on Established Type-1 Diabetics

 
Of these treatments 14 (23%) are being tested on people with established T1D, of those, 9 are funded by Breakthrough T1D.  So 64% of the trials recruiting people with established T1D are funded by Breakthrough T1D.

Compared to Last Year
In 2023 there were 59 treatments in clinical trials, in 2024 there are 62 (growth of 5%).

In 2023 there was 2 treatments in Phase-III trials, in 2024 there are 3 (growth of 50%).
In 2023 there were 17 treatments in Phase-II trials, in 2024 there are 19 (growth of 11%).
In 2023 there were 14 treatments in Phase-IIΔ trials, in 2024 there are 19 (growth of 36%).
In 2023 there were 25 treatments in Phase-I trials, in 2024 there are 21 (dropped by 16%).

I think that the drop in Phase-I trials was mostly caused by me doing a good housecleaning to remove old, moribund trials, when I had not done that in several previous years.

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 nPOD, Immune Tolerance Network, and INNODA and so I give Breakthrough T1D credit for clinical trials based on their work.

 

How I Count Trials for This Comparison

• I don't count trials where the Breakthrough T1D funded some basic research, but not the research which lead to a specific clinical trial.  I'm sure this under estimates JDRF's impact.  For example OPT101 is an anti CD154 drug.  JDRF has funded many studies on CD154, but not the particular research that is being tested here.  Similarly with Ixekizumab, JDRF has funded related research on that drug, but not the clinical trial or the research immediately leading to the clinical trial here.
  
• 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. 
• 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. 
  

Research Not Listed Here

I sometimes get asked why some piece of research is not listed here, and so here are some of those answers:

• VX-880 is a transplant study which requires life long immunosuppression.  Read here why I do not consider these to be cures.
• Levicure's Combination Therapy has only been tested in a retrospective study, not an intervention based clinical trial.

Some Specific Notes:

• 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 fifteen years.  Below is a link to last year's, but you can search for "JDRF Funding for a Cure" for the rest of them:

• https://cureresearch4type1diabetes.blogspot.com/2023/11/jdrf-funding-for-cure-2023.html

Please remember that my blog (and therefore this posting) covers research aimed at curing, delaying, 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 Breakthrough T1D 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

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 kid 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.

Fenofibrate Is Unsuccessful In A Phase-IIΔ Trial In Honeymooners

Fenofibrate (also spelled Phenofibrate) is commonly prescribed for high cholesterol and high triglycerides. In 2017, it was the 70th most commonly prescribed medication in the United States with more than eleven million prescriptions.  However, it is not approved for use in children under 18. It is also sometimes prescribed for diabetic retinopathy (eye damage from long term diabetes), and (off label) for gout.

However, it also showed some promise in NOD mice (an animal model for T1D), and so one person took it "off label" when they were diagnosed with T1D as a 19 year old.  They did not need to inject insulin for years after that, a huge result.  Still later, some researchers started a Phase-IIΔ trial.  These are my previous blog posts on Fenofibrate:

https://cureresearch4type1diabetes.blogspot.com/search?q=Fenofibrate&by-date=true

I had high hopes for this research.  I try not to become emotionally attached to specific research, because it clouds my judgement and because most research fails.  However, having one person go years without having to inject insulin was so good, and so unusual, that I was hopeful.  Unfortunately, this research did not pan out.

Results From the Phase-IIΔ trial

Here is the conclusion from the result's abstract:

Contrary to the beneficial effects of fenofibrate found in preclinical studies, this longitudinal, randomized, placebo-controlled trial does not support the use of fenofibrate for preserving beta cell function in individuals with newly diagnosed type 1 diabetes.

Since my initial excitement was based on a person who did not need to inject insulin after taking Fenofibrate, it makes sense to look at the insulin use and compare the people who got the drug (in red below) with the people who got the placebo (in blue).  You'll notice that the people who got the drug used a little more insulin.  This is the exact opposite of success, although the difference was not statistically significant.  Bottom line: it did not work.

Journal Article: https://www.researchgate.net/publication/385385677_Effect_of_fenofibrate_on_residual_beta_cell_function_in_adults_and_adolescents_with_newly_diagnosed_type_1_diabetes_a_randomised_clinical_trial/link/6722f02decbbde716b4c5777/download

This study used the same dose (160mg/day) that the successful "off label" used.  And that person stopped taking insulin after 19 days, so this study lasted much longer than needed to see the effect.  Also, the "off label" use started 7 days after T1D diagnosis, while this study started, on average, 22 or 24 days after diagnosis, with a standard deviation of 10 or 11 days.  The number of people who were "in remission" of T1D during their honeymoon was higher in the placebo group than in the treated group.  I put "in remission" in quotes because it is not what most people would consider remission.  They still used a little insulin, just not very much.  The researchers used a formal, technical definition of remission called the ADDRESS-2 definition, which is quite different than what you or I would call remission.

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 kid has type-1 diabetes and has participated 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!

Encellin Starts a Phase-I Trial of ENC-201-CED (Encapsulated Beta Cells)

The company Encellin has started a Phase-I clinical trial to test ENC-201-CED an encapsulated beta cell product.

Encapsulated Beta Cells In General

Encapsulated beta cells are implanted devices.  The encapsulation allows blood sugar in, and insulin out, but does not allow the body's immune system to attack the beta cells. It also allows nutrients in and waste products out. This allows the beta cells to naturally grow and to react to the body's sugar by generating insulin which goes into the body's blood system. Meanwhile, the body's autoimmune attack cannot target these beta cells, and you don't need to take any immunosuppressive drugs (as you would for a normal beta cell transplantation).  The cells inside the encapsulation can come from different sources, depending on the company creating the product.

Encapsulated beta cells seem like a straight forward cure for type-1 diabetes, but companies have been working on them since the 1990s, without creating a cure.  There appear to be several difficult problems to solve, especially getting oxygen to the new cells.   Bottom line is this: while encapsulated beta cells sound like a "just needs engineering" cure for type-1 diabetes, decades of work has not led to a cure yet, so it is obviously harder than it looks.

I have blogged at least 10 times over the last 15+ years on different encapsulated beta cell approaches:

https://cureresearch4type1diabetes.blogspot.com/search/label/Encapsulated%20Transplant

This Study

This study will recruit 10 people between 18 and 70 years old.  Everyone will get the treatment.  There is no control group.  Everyone will be followed for about 4 months.  This is strictly a safety/tolerability test.  They are measuring adverse effects and how well the implant takes.  They are not measuring effectiveness.  Even in the secondary outcome measures there are no tests for A1c, Blood glucose, C-Peptide, or time in range.

The study started in March 2024 and they hope to finish in December 2025 and publish by July 2026.

Other than that, their clinical trial registry is very sparse, and I cannot find any information on the trial on the web site of the hospital which is actually running it.  Therefore, I don't know the exact requirements to participate in the study, how many operations are required, what sort of immune suppression is being used (if any), or how man encapsulated beta cells (or devices) will be implanted.

Contact Information:

Study Contact: Phone: +1-650-434-0987  Email: info@encellin.com

Study Contact Backup: resCON Research  Email: info@resconresearch.ca

They are recruiting at one site:

McGill University Health Centre Montréal, Quebec, Canada, H4A 3J1

Contact: Lin Jawhar

Principal Investigator: Steve Paraskevas, MD

Clinical Trial: https://www.clinicaltrials.gov/study/NCT06408311

Discussion

I usually don't comment on company funding because I have found that it doesn't matter who funds research.  Sometimes big name companies fund failures and people I've never heard of fund successful research.  However, I will say that Encellin is mostly funded by Khosla Ventures, which is a big name in Silicon Valley venture capital.  Also, Encellin was incubated by Y-Combinator, which is a big name "factory" of Silicon Valley start ups.  These guys would be Silicon Valley royalty, if Silicon Valley had royalty.

Company's Web Site: https://www.encellin.com/

History

About 7 years ago, there was a lot of excitement about research done at Tejal Desai's lab at UCSF.  Several people asked me about it and at least one person lobbied for me to write a blog on it.  There was widespread hope that this research would lead to a cure in a few years.  There was widespread belief that it would lead to clinical trials sooner than that.

I didn't blog on it because my policy is to wait until recruiting has started on a clinical trial (a test done on people).  Seven years ago, all we had was very optimistic press releases.  But now, finally, this clinical trial is the follow on to Tejal Desai's work all those years ago.  They have started a clinical trial on this technology and so I'm blogging on it.

Remember this when you are frustrated because some research that you heard very positive things about never seemed to go anywhere.  First, a lot of very positive sounding research never does go anywhere.  That is the normal nature of research.  Second, even when it does, it takes many years.  The successful out come still takes many years.

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 kid has type-1 diabetes and has participated 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!

Frexalimab Starts A Phase-IIΔ Clinical Trial (FABULINUS)

There are two good reasons to test Frexalimab as a cure or treatment for Type-1 Diabetes (T1D).  The first is that it has shown some effectiveness in treating Multiple Sclerosis (MS).  MS is an autoimmune disease, generally similar to T1D, except that the immune system in MS attacks nerve cells rather than beta cells.  So the thinking goes, if it works for MS maybe it will work for T1D. 

The second reason is more direct, but also a little more complex to explain.  You can think of the immune system as being a large collection of different cells, often with CD or IL names.  These cells interact in various ways to attack (or ignore) certain cells.  Many immune responses are controlled by a balance between two different types of cells.  One of these two-cell balance points is between CD40L/CD154 cells and CD40 cells.  CD40L and CD154 are two different names for the same kind of cell and it balances the CD40 cell.  They balance each other so the the immune system is aggressive enough to attack foreign cells, but not so aggressive as to attack the body's own cells. Frexalimab is a Monoclonal Antibody which is an antagonist to CD40L.  That means it blocks the activity of CD40L cells in the immune system.  The researchers involved have been looking at the balance between CD40L/CD154 and CD40 as part of the pathway causing T1D for at least 20 years.  There is a lot of research showing that CD40L (and the relationship between CD40L and CD40) is important to the path that leads to T1D.  Therefore, it makes a lot of sense to test drugs that impact CD40L.

The FABULINUS Study

This study is enrolling almost 200 people between 12 and 35 years old and within 90 days of T1D diagnosis.  This is a randomized, controlled, blinded clinical trial with four groups (three different Frexalimab doses and a placebo).

People will get Frexalimab for a year, and then be followed for another year, and then there is the possibility of another follow up for another half year.  Frexalimab will be given once intravenously (needle into a vein), and then weekly subcutaneously (injected under the skin, like insulin). The primary end point is C-Peptide after a year, and there are a bunch of secondary end points including C-Peptide at other times, blood glucose time in range, insulin usage (including what they call "remission"), and several other safety and effectiveness measures.

This study started in Dec-2023 and they hope to complete it by Nov-2028.

This study is huge, recruiting at 34 different locations (12 in the US, 2 in Canada, and 20 in Europe).  The official contact information is:
Phone Number: 800-633-1610 ext. option 6
Email: contact-us@sanofi.com

Web Pages:  https://www.innodia.org/fabulinus-trial and https://www.sanofistudies.com/us/en/listing/312876/frexalimab-in-preservation-of/

Clinical Trial Registry:  https://clinicaltrials.gov/study/NCT06111586
Poster: https://diabetesjournals.org/diabetes/article/73/Supplement_1/2021-LB/156038/2021-LB-FABULINUS-A-Randomized-Controlled-Trial
Buy In Bulk: https://www.medchemexpress.com/frexalimab.html

Discussion

It is clear that the researchers have very high hopes for this treatment.  Three of their secondary end points include:

• Proportion of participants with A1c ≤6.5% and requiring no injections of exogenous insulin after 1 year or 2 years.  This would be a practical cure: a non-diabetic A1c number without injecting insulin.
• Proportion of participants in "partial remission" which they define as insulin dose-adjusted A1c score ≤9.0, where it is calculated as A1c + 4x insulin dose when measured as IU/kg/day.  So that means that if a person weighs 50 kg / 110 lb, and is injecting 10 units of insulin per day and has a A1c of 7, their adjusted A1c would be 7 + 0.2 x 4, which is 7.8 which is below 9 and is in "partial remission", as defined here.  The 0.2 comes from 10 (units of insulin) / 50 kg per day.
• Proportion of participants with A1c ≤6.5% and requiring ≤0.25 IU per day per kilo of insulin after 1 year or 2 years.  Using the same 50 kg / 110 lb kid as an example, he or she could inject up to 12 units of insulin per day and still meet this criteria of success, if their A1c was low enough.  That would be a great outcome although not a cure by my definition.

All of these results would be measured both one and two years after the study starts.  The second year, is well after the honeymoon has ended.  These secondary end points are incredibly optimistic.  The first bullet point is a practical cure!  If they get even two or three people in that category, two years after diagnosis, this will be the most successful trial I can remember.

A quick summary of Frexalimab's status for other diseases is this paragraph from a Royal Pharma press release.  This sounds very optimistic, but remember that Royal Pharma has invested in Frexalimab, so they are not objective observers!

Frexalimab, in development by Sanofi, is a first-in-class, second generation anti-CD40 ligand monoclonal antibody. Frexalimab is in three Phase 3 clinical studies for the treatment of multiple sclerosis (MS). Phase 2 clinical studies for systemic lupus erythematosus and Type 1 Diabetes are ongoing. ... Sanofi anticipates filing a biologics license application (BLA) for relapsing multiple sclerosis with the U.S. Food & Drug Administration in 2027.

Source: https://www.royaltypharma.com/news/royalty-pharma-to-acquire-royalty-interest-in-sanofis-frexalimab/

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 kid has type-1 diabetes and has participated 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!

The full story on "Stem cells reverse woman’s diabetes — a world first"

If you've been reading news recently you might have seen headlines like these:

Stem cells reverse woman’s diabetes — a world first

Stem Cell  treatment reverses Type 1 Diabetes!

Chinese scientists have put a young woman’s type 1 diabetes into full remission using stem cell treatment.

And even if you didn't your friends and relatives might have seen them and asked you about them.

(And that first one is from the journal Nature, which is a major scientific publication.)

Unfortunately, those headlines are basically hype.  There is some news, and it is good news, showing important progress, but it is no where near as good as the headlines make it sound.

What Was Reported

The researchers took some adult stem cells from a person with type 1 diabetes, and treated those stem cells with a specific recipe of drugs, which caused them to change into beta cells.  They then implanted those cells back in the person who donated them.  The results were spectacular.  After about 2 months the person stopped injecting insulin, and then was followed for another 10 months without needing any injected insulin.

The woman was not your average person with T1D.  She had been diagnosed 11 years prior, so was well established.  However, she had previously had two liver transplants and one pancreas transplant (more on that below).  At the end of a year, her A1c was 5% and her blood glucose time-in-range was 96%, both great numbers.

Not A Cure

Before getting this transplant, this person had already had several transplants, and was therefore on immunosuppressive drugs and would need to stay on those drugs for the rest of her life.  Therefore, by my definition, she was not cured but rather traded one treatment (insulin for T1D) for another treatment (immune suppression for a transplant).  I don't consider this a cure.  Some people may prefer one drug regimen over another, but it is not clear to me that one is generally better than the other.  My understanding is that people who have whole life immune suppression generally have shorter life spans than people with T1D.  

But in any case, I don't consider this a cure.  Of course, you may, and if you do, then you should look into existing transplantation surgeries, because there are some available now that have similar results to what is seen here.

Shows Progress

The big headline "no insulin injections for almost a year" is misleading because those results have been seen previously in transplants when whole life immune suppression has been used.  The JDCA has published two great overviews in 2016 and 2022, which you can read here:

• https://www.thejdca.org/publications/report-library/archived-reports/2016-reports/islet-cell-transplantation-update-new-phase-iii-study-results-show-insulin-independence-unchanged.html
• https://www.thejdca.org/publications/report-library/archived-reports/2022-reports/pioneering-islet-cell-transplant-team-publishes-20-years-of-data.html

The bottom line is that no insulin injections for a year occurs in half the cases, and for two years in over 40% of the cases.  So the headlines are hyping something we can already do. (If you are willing to suppress your immune system for the rest of your life.)

If fact, there is an FDA approved transplant protocol, where over 2/3s of the people did not have to inject insulin for more than a year, but it does require immune suppression:

https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-type-1-diabetes

However, the research reported here does show some specific progress, and some strong future possibilities.  The key improvements seen here are:

1. More stem cell availability.  Previous transplants have used beta cells from cadavers, pigs,  occasionally live doners, and just recently from the patient themselves.  This research sources beta cells from the patient, which means there will always be a strong supply.  The treatment that they use to mature the stem cells into beta cells is new and unique and the researchers claim it is much better than previously available techniques.  They think it gives them more control over the resultant beta cells and also is more effective.  It is this technique that is the real progress.

2. Using a person's own stem cells.  My memory is that this is not the first ever case where T1D  transplantation used cells from the person being treated.  However, this is a very recent and experimental technique.  The success here is important.  Most importantly, there is hope that these cells will not be automatically attacked by the person's immune system, because they are not foreign.  This is a serious issue with other transplants.  Because these cells are not foreign, this transplant may not require long term immune suppression.  That would be a huge breakthrough.

Unfortunately, since this person is already using long term immune suppression, there is no way to know from this trial if this kind of immune suppression is needed or not.

Furthermore, even if this procedure becomes immune suppression free in the future, it is not clear what will happen to the new beta cells long term without it.  Will the person's T1D immune system attack the new beta cells just like it attacked the original ones?   We don't know.  That is future research that must be done.

There are four hopeful possibilities here (lines of research which might prevent this attack).  They are theories held by some researchers.  The first two are active areas of research, with several research groups working on each one, and the second two are tested on occasion, but are less actively pursued:  

1. Several research groups are investigating encapsulation, so that the immune system cannot physically get to the new beta cells, which would protect them.
2. Other groups are developing the process of converting stem cells to beta cells so that the new cells were invisible to the immune system and protected that way.  The immune system tends to focus on very specific structures in the "skin" of the cell to identify what to attack.  If those structures are missing, then maybe the immune system would ignore the new cells.
3. The trigger of the autoimmune attack on beta cells might be time specific.  It occurs at a specific time for a specific reason.  So therefore, years later, when the new cells are transplanted, the trigger is no longer there and the cells will not be attacked.  
4. Finally, the immune attack on beta cells might be location specific.  It occurs because of the situation in the pancreas specifically.  Therefore beta cells not implanted in the pancreas won't trigger the immune response.

The researchers were waiting for results from the first person, but now that they have them, they will start up two more people.  It is a little hard to tell, but I suspect these two people will also have prior transplants and therefore long term immune suppression.

The study is ongoing and they are recruiting more people with T1D in Tianjin, China.  The study is described as "Phase 0", but I don't know what that means in China.  It is similar to an American phase-1 "pilot" study: no control group, no blinding, three people who will be followed for two years (I think) after transplantation.  Primary end point is A1c.  Secondary end points are C-Peptide and insulin use.

Contact: Wang Shusen        +86 136 1218 3907  shusen1976@126.com

               Shen Zhongyang  +86 138 0301 9898  zhongyangshen@vip.sina.com

More Information

This research was published in the journal Cell, which is a big name scientific journal:

https://www.cell.com/cell/abstract/S0092-8674(24)01022-5

JDCA's report: https://www.thejdca.org/publications/report-library/archived-reports/2024-reports/established-t1d-patient-insulin-independent-is-it-really-a-practical-cure.html

Chinese Clinical Trial Registry: https://www.chictr.org.cn/showproj.html?proj=192835

WHO Clinical Trial Registry: https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300072200

Coverage: https://www.sciencedirect.com/science/article/abs/pii/S0092867424010225

General Article: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-024-03636-0

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 kid has type-1 diabetes and has participated 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! 

Combo of Rituximab and Abatacept Starts a Phase-II In Honeymooners (T1D RELAY)

Rituximab is FDA-approved to treat several autoimmune diseases, including Rheumatoid Arthritis (RA).  About 10 years ago there were a couple of clinical trials testing it for T1D, and the results were medium-good. I blogged on those: https://cureresearch4type1diabetes.blogspot.com/search/label/Rituximab

Abatacept is FDA-approved to treat adult Rheumatoid Arthritis, as well as Juvenile Idiopathic Arthritis (JIA) in children as young as six.  I blogged on those: https://cureresearch4type1diabetes.blogspot.com/search/label/Abatacept but not on the most recent results, which are here: https://diabetesjournals.org/care/article/46/5/1005/148547/Abatacept-for-Delay-of-Type-1-Diabetes-Progression and were unsuccessful on the primary end point, but some interesting data on the lessor end points.

Rituximab suppresses CD20 cells, which are a subset of the immune system's B cells (different from the pancreas's beta cells).  Hopefully this will block the autoimmune attack. B cells communicate with the T cells, which actually attack the body's beta cells in the pancreas. By targeting the B cells, it is hoped this treatment will stop or lower the attack of the T cells.

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.  

So you can see how these two drugs can work together to have a stronger effect than either alone.

The Study

This study will enroll 76 honeymooners (within 100 days of diagnosis), between 8 and 45 years old.  Everyone will be treated with Rituximab once a week for 4 weeks.  This is an IV infusion which will take 3-8 hours. There is then a 3 month period without treatment, and then 2/3s of the people will get Abatacept.  That is a weekly injection (much like injecting insulin) which will go for 20 months.  1/3rd of the people will get a placebo and be the control group.  (So everyone gets Rituximab, but not everyone gets Abatacept.)

Everyone will then be followed for a total of 4 years, so 2 years after the last treatment.  The primary end point is C-peptides and secondary endpoints include immune measurements to see how the treatment effects people.

The study started in Oct-2023 and is expected to end between Oct-2027 and Oct-2029.  However, since they are still recruiting, and the study follows people for 4 years, I don't see how it can finish before mid-2028.

They are recruiting in 13 locations in the United States plus Melbourne, Australia.  The full list is in the clinical trial link below or you can get in touch with the study contacts:
Ariana Rojas  +1-813-974-682    ariana.rojas@epi.usf.edu
Melissa Parker  +1-813-396-9378   melissa.parker@epi.usf.edu 

Web Site: https://www.trialnet.org/our-research/newly-diagnosed-t1d/t1d-relay
Clinical Trial Registration: https://www.clinicaltrials.gov/study/NCT03929601

Discussion

This study tries to combine two treatments with lackluster results into something better.  Of course, I have no idea if it will work, but if it does, that is good news in two different ways.  First, as a promising honeymoon treatment to delay or even prevent T1D, that is the direct goal of this trial.  But second, many researchers believe that two different immune drugs (with two different mechanisms) might be a lot better than one immune drug alone.  They may interact synergistically.  A success here would show that two drugs together could be much more than either one alone, and that could open the flood doors of combination drug trials.

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 kid has type-1 diabetes and has participated 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!

 

Abrocitinib and Ritlecitinib Start A Phase-IIΔ Clinical Trail in Honeymooners (JAKPOT)

(Note: JAKPOT is a name of at least two different clinical trials.  If you are reading about a French clinical trial targeting Rheumatoid Arthritis, that is a different clinical trial.)

The site's web page describes the drugs involved this way:  Abrocitinib and Ritlecitinib are in a new class of autoimmune treatments called Janus kinase (JAK) inhibitors.  Abrocitinib is approved by the U.S. Food and Drug Administration (FDA) to treat eczema. Ritlecitinib is being studied as a treatment for several autoimmune diseases, including Alopecia, Ulcerative Colitis, Crohn’s Disease, Vitiligo, and Rheumatoid Arthritis.

Researchers believe Abrocitinb and Ritlecitinib may be able to calm the immune system response that harms beta cells.  Located in the pancreas, beta cells are responsible for making insulin.  Continuing to make even a small amount of insulin helps keep blood glucose levels in the normal range, lowering the risk of long-term complications.

The Study

This study enrolls 78 people in three groups: a placebo group, an Abrocitinib group and a Ritlecitinib group.  The drugs are in pill form and people will get them for a year and then be followed for another year.  The are recruiting Honeymooners (within 100 days of diagnosis) who are 12 to 25 years old, and will be measuring C-peptides as primary end point.  No secondary end points are listed (which is very unusual, but I don't know what it means).

The study started in October 2023 and is expected to finish in June 2026, but that is dependent on successful recruiting.  They are recruiting at a total of 15 locations in the United States, including both UCSF and Stanford.  Here is contact information: 

Jessica S Conaty  +1-813-396-9234  Jessica.Conaty@epi.usf.edu
Melissa Parker  +1-813-396-9378  Melissa.Parker@epi.usf.edu

Web Page: https://www.trialnet.org/our-research/newly-diagnosed-t1d/jakpot-t1d
Clinical Trial Registry: https://clinicaltrials.gov/study/NCT05743244

Discussion

I have previous reported on another JAK inhibitor (Baricitinib), which had medium-good results in a phase-IIΔ study:
https://cureresearch4type1diabetes.blogspot.com/2024/01/results-from-phase-ii-baricitinib.html
and there is a lot of interest in JAK inhibitors in general for a wide variety of immune and autoimmune diseases.  The American Diabetes Association scientific sessions (held last month) had several talks, papers, and posters on JAK inhibitors.

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 kid has type-1 diabetes and has participated 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.