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.

 

BMF-219 Starts a Phase-IIΔ

BMF-219 is a drug that inhibits Menin, a protein.  Menin's functions in cells are not fully understood, and may be complex and contradictory.  For example, Menin is generally a tumor suppressor, but inhibiting Menin is a treatment for certain acute leukemias.  It is being developed by Biomea for T1D because it "is thought to act as a brake on beta-cell turnover and growth, supporting the notion that inhibition of Menin could lead to the regeneration of normal, healthy beta cells" according to the company's web site. 

The Study

The trial started in 2023, and is expected to finish in Sept-2025. It will enroll 150 people (mostly) within three years of diagnosis.  Everyone will get BMF-219 for 12 weeks and will be followed for one year.  The study design is a little complex, and the public description of the trial does not include how many people will be involved in each part, but the study has 3 parts, each with its own groups:

• The main study is blinded and has a total of three groups with different doses: 100mg, 200mg, and placebo.  These people will all be within 3 years of diagnoses.
• Substudy 1 is open label and has two dose groups: 100mg and 200mg, and also be within 3 years of diagnosis. 
• Substudy 2 is also open label with the same two dose groups, but includes people who were diagnosed between 3-15 years ago, but have slightly higher C-peptide generation than those in the main study or substudy 1.

For all parts, the primary end point is C-peptides, and the secondary end points include more C-peptide numbers, A1c numbers, insulin usage, and adverse events.  

The people to contact if you want to enroll in this study are Cristina Guzman and Michelle Stevens-Brogan, who are both at clinicaltrials@biomeafusion.com and +1-844-245-0490.  They are running the trial at a total of 11 locations in the US and 2 in Canada.  The list is in the clinical trial record (but none in California).

Clinical Trial Record: https://clinicaltrials.gov/study/NCT06152042

Discussion

My opinion is that the complex study design is to allow Biomea to have a small group where they can publish results relatively quickly (substudy 1) while also having a larger group (main study) which can deliver blinded (and therefore higher quality) results.  For me, this seems similar to how the company designed its T2D study, which I describe below.  The substudy 2 results can give them an early indication of effectiveness on people with established T1D, instead of honeymooners.

This strikes me as a very smart way to do a clinical trial if you have enough money. You file one set of paperwork and technically run one trial.  However, from that one trial you get quick data to use for marketing, slower but stronger data for eventual drug approval, and a little taste of data for a future development direction.  Very efficient.

Honeymoon or Established?

One question is, why recruit people within 3 years of diagnosis, when the honeymoon period is generally assumed to be a year or less?  Of course, I don't know the answer, but this is my best guess as to what is going on: The actual recruitment criteria include within 3 years of diagnosis and generating a little of your own insulin (and some other requirements).  This is pretty common.  But it may be that the researchers think that generating a little of your own insulin is the important part, and when that ends, the honeymoon ends, and the years matter much less.  As a practical mater, everyone will be within a year of diagnosis, because those are the only people who are generating enough insulin to enter the trial.

Another interesting question is: will a drug like this work better on honeymooners or established T1D?  The answer is not as simple as you would think.  Everyone agrees that T1D is caused by the immune system mistakenly attacking beta cells (which normally generate insulin).  When enough beta cells are destroyed, insulin production drops, and T1D is diagnosed.  But there are two open questions: (1) Is the immune attack a limited event that ends at some point in time?  And (2) does the body continue to naturally regenerate beta cells?

Most researchers believe that the immune attack continues for a person's whole life, and that natural beta cell regeneration is either nonexistent or really tiny.   If both of those assumptions are true, then this treatment is likely to have a stronger effect in extending the honeymoon, than curing established T1D.

But there are other scenarios: If the immune attack ends, but the body does not regenerate beta cells, then this treatment might cure established T1D, but not honeymoon T1D.  Because bMF-219 causes the beta cells to regrow after the immune attack has eneded.   On the other hand, if the immune attack is ongoing, then this probably will not cure established T1D, but might extend the honeymoon, depending on the relative strength of the immune attack vs. the treatment's effectiveness at regenerating beta cells.

Previous T2D Trial

Biomea had previously started a clinical trial on people with T2D, and published results from a very small (about 20 people) initial group.  Those results seemed very slightly positive to me, but I'm not used to evaluating T2D studies.  The entire trial (about 420 people) is expected to finish sometime between mid-2024 and mid-2025.

Of course, even if the results from a T2D trial are very positive, that does not mean it will work for T1D.  This is especially an issue for BMF-219, because if the T1D immune system attack on beta cells is still active, regenerating "normal, healthy beta cells" may have no effect as they are destroyed by the body's own immune system, same as the previous beta cells.  However it would tell us if the body naturally regenerated beta cells.

Biomea is also running two more clinical trials where BMF-219 is tested to treat cancers.

DiaTribe is a great source of information on diabetes research, and they covered both BMF-219 trials here, but focused on the T2D one:
https://diatribe.org/clinical-trial-tests-new-technique-stimulate-beta-cells

Corporate Web Site: https://biomeafusion.com/

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.

 

Fenofibrate Starts A Phase-IIΔ Trial

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.  I blogged on this:
https://cureresearch4type1diabetes.blogspot.com/2020/06/strong-results-from-single-case-use-of.html
with an update:
https://cureresearch4type1diabetes.blogspot.com/2021/03/possible-cures-for-type-1-in-news-march.html

The Study 

The good news is that this study started in Sept-2022 and is scheduled to finish in July-2024.  However, the US registry lists them as still recruiting.  If this is true, completion will be delayed.  The European registry does not differentiate between recruiting and active, not recruiting.

The study includes about 100 children (10 to 17 years old) divided into two groups: one gets 160 mg Fenofibrate and one gets placebo.  This is a once per day pill given for a year.  The study is randomized and blinded.  The primary result is C-peptide and secondary results include more C-peptide numbers, insulin usage, adverse events, A1c, and several immunology measures.

European Clinical Trial Record: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003916-28/PL
US Clinical Trial Record: https://clinicaltrials.gov/study/NCT05909800

Discussion

This is exactly the kind of study I want to see for Fenofibrate, and I'm very excited to see its results. 

There are two trials of Fenofibrate in people with T1D which are currently running.  The first is designed to prevent kidney function loss rather than cure/prevent/delay T1D itself and therefore I have not been following it.  It is NCT04929379.  They are enrolling 40 adults with T1D for at least 8 years and have diabetic kidney disease.  It started in 2022 and they hope to finish in 2025.  No intermediate results have been published, and I don't expect any.  But the bigger issue is that all their end points involve kidney function.  They are not measuring C-peptide, A1c, or insulin use at all.  So even if the medicine had a big impact, they would not see it.

The second is designed to prevent rather than cure/prevent/delay T1D itself, so I have not been following it, either.  It is NCT01320345.  They are enrolling 450 (!) adults with T1D and have eye problems.  It started in 2016 and they hope to finish in 2025.  No intermediate results have been published, and I don't expect any.  But the bigger issue is that all their end points involve eye function.  They are not measuring C-peptide, A1c, or insulin use at all.  So even if the medicine had a big impact, they would not see it.

Personal note: I try not to get excited about potential T1D cures.  I think treating all potential cures dispassionately is better for me and better for this blog.  (Plus, my child was diagnosed over 22 years ago, so getting excited would not have panned out.)  But I am human, and I do sometimes get excited.

I am optimistic about Fenofibrite potential to prevent T1D in the honeymoon phase.  I can't explain exactly why this honeymoon treatment and no other.  Maybe it is because it really seems to have worked for one person, for many years, and (as yet) there is no clinical trial results to dampen my enthusiasm. 

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!

 

 

 

Siplizumab Starts Two Trials in Honeymoon T1D (DESIGNATE and STRIDE)

Siplizumab (MEDI-507, TCD601) is an monoclonal antibody which targets CD2 cells in the immune system.  It is being developed by ITB-MED.  It has an active research program for several different diseases with about 20 clinical trials in process.  There are currently two clinical trials targeting Type 1 Diabetes, so I'll discuss each in turn.

Part of the motivation to test Siplizumab was a previously good result from Alefacept.  I blogged about that result here:
https://cureresearch4type1diabetes.blogspot.com/2016/02/alefacept-reports-on-phase-ii-results.html
You can read my conclusions in the previous blog posting, but the company that made Alefacept stopped marketing the drug, which had been approved for Psoriasis, because of newer drugs in the field.  The hope is that Siplizumab will work in the same way and have similar results.

DESIGNATE: Phase-IIΔ Siplizumab in [Mostly] Honeymooners

This trial was started by the US government (National Institutes of Health, National Institute of Allergy and Infectious Diseases) and is being run by the Immune Tolerance Network.  It started in April-2023 and they are enrolling 120 people, which is a lot.

Initially adults were enrolled, but later the study started enrolling children as young as 8.  Everyone is within 18 months of diagnosis.  This is an open label trial, where each person will get one of four different doses of Siplizumab.  No placebo or control group.

The primary end points for this study look at changes in immune cells, so they are measuring how the treatment changes the immune system.  The secondary end points include adverse effects, C-peptides, and insulin use, and so cover both safety and effectiveness.

This study is in a pause right now.  They are evaluating the results from the first couple of people, and may change the study slightly based on what they learn.  When it moves forward, they will be recruiting at 20 locations all over the US, which will be listed in the links below:

Trial Web Page: https://www.designate-study.org/
Clinical trial registry: https://clinicaltrials.gov/study/NCT05574335

STRIDE: Phase-IIΔ Siplizumab in Honeymooners

This trial was started by a company (ITB-Med LLC), and is run by INNODIA.  It started in Jan-2023 and expects to finish in Jan-2025.  They are enrolling 96 adults. 

People must be within 100 days of diagnosis to be enrolled.  I think that there are four treatment groups, with one getting a placebo and the other three each getting a different dose of Siplizumab.  Nowhere are the doses listed.  Patients will get the treatment for 12 weeks; I think 1 dose per week, and will be followed for a year total. 

Although the description is a little vague, I think this study measures C-peptide as its primary end point, and adverse reactions as its secondary end point.  The first covers effectiveness and the second covers safety.

This study is still recruiting in Europe (Belgium, Germany, Italy, Poland, UK).  You can see the exact locations in the clinical trial registry: https://clinicaltrials.gov/study/NCT06025110

Eudract number: https://www.clinicaltrialsregister.eu/ctr-search/trial/2022-001713-39/SE

Discussion

These clinical trials have a lot in common.  The differences I do see are:

1. The STRIDE study recruits people within 100 days of diagnosis, while DESIGNATE recruits people within 18 months of diagnosis.
2. The STRIDE study recruits adults only, while DESIGNATE started out recruiting adults, but later added children.
3. STRIDE is single blind, DESIGNATE is open label. 
4. My understanding is that the two studies use different dosing techniques. 
   

An obvious question is: why did two different studies start at almost the same time, which are so similar?  I don't know the answer.  Both studies were motivated by the same company, the one producing the drug, and I'm always in favor of doing more studies, more quickly.  I'm happy they are moving forward along two separate paths at the same time.

One issue in the DESIGNATE trial is the recruitment cut off of 18 months after diagnosis.  I don't understand that.  The honeymoon time period is generally accepted to end after 12 months or a little earlier, so this means that DESIGNATE will include some honeymooners and some non-honeymooners.  I can only hope that they will analyze the data for both people recruited in their honeymoon phrase and separately for people who are not, just in case it works at one time but not at the other.

I'm not sure of the details of the history of Siplizumab, but I think it was originally developed by MedImmune,which was later bought by AstraZeneca.  However, the rights were later bought by ITB-Med, who are responsible for testing the drug on people with T1D. 

The Immune Tolerance Network, which is running DESIGNATE, is a collaborative network for clinical research, funded by the National Institute of Allergy and Infectious Diseases, part of the [United States] National Institutes of Health (especially through the special type 1 diabetes appropriation), and JDRF.

INNODIA, which is running STRIDE is a European non-profit network dedicated to preventing and curing type 1 diabetes.  It is funded by the European Commission’s Innovative Medicines Initiative (IMI-JU Joint Undertaking), The Hemsley Charitable Trust, JDRF, and EFPIA partners.

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!

Why I Don't Blog On How To Vote For T1D (part 1)

This whole blog posting is very US (and US politics) focused, but the issues are similar in other countries.  Also, this blog is trying to describe the existing situation, not argue that the current situation is good, bad, or should be changed.  It is just describing how things are.

When I first starting blogging, over 15 years ago, I thought it might be a useful idea to have a "Voter's Guide To T1D" style blog.  I would discuss who to vote for if all you cared about was T1D, why one candidate was the best for T1D research, how your vote would impact T1D research, and so on.  I never quite got around to it.  Since then, I've changed my opinion and decided that such a blog could never be written because T1D should not effect how people voted.

As people affected by T1D, we should want two things from our government, which means two things to consider when we vote.  One is the best possible care for T1D and the other is the best possible research into finding a cure for T1D.  Some people are more care focused, and others more cure focused, but those are the biggest T1D issues out there.

The democratic way to view this is to ask the question:  "if T1D is important to me, who should I vote for to improve these things."  The idea is that your vote should be directed by what you care about.  My insight is that is not true, because your vote is actually about how to solve problems, not what problems are important.

For example, consider research.  In the US, more liberal people think that research can be encouraged by funding research.  More conservative people, by lowering regulation of research. Neither of these groups are for or against research, they differ on how to encourage it.

Obviously, the perfect person to vote for is someone who cares about T1D and who has the same political leanings as you, and obviously the worse person to vote for is someone who doesn't care about T1D and has the opposite political leanings as you. 

However, in choosing between someone who has your political leanings, but does not care about T1D and someone who does not have your political leanings, but cares a lot about T1D, who should you vote for?  The answer is: you should choose the person with your politics.  (And this is true even if you are a single issue voter, and that issue is T1D.)

Why?  Because the person who does not share your politics will do things that they think will help T1D, but you will not agree with, even for T1D.  For example, if you are a liberal who cares about T1D, but vote for a conservative because they care a lot about T1D, they are going to lower government regulations on big businesses.  And you are going to think, it just encourages businesses to fleece me and not do any more research. 

Therefore, you should vote your own politics and not vote for who "cares" more about T1D, unless it is a primary and both politicians have your politics in general, and it is just a question of more or less T1D.  If you have that luxury, definitely vote more T1D!  However, that assumes the choice is between to people who otherwise share your views.

In the past, there might have been politicians who were generally liberal, but conservative on T1D research, or the other way around, so you might want to vote for them because they matched your T1D views, even if they did not match your more general views.  But I think those politicians are rare to nonexistent today.  Today, politicians are either liberal about nearly everything or conservative about nearly everything.

So therefore, blogging about a particular politicians positions on T1D is a waste of time.  The important thing is their general politics, and others can blog on that much better than I can.

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.

Diamyd Update Part 2: JDRF Flexibilty In Funding and Diamyd In More People

My previous blog posting:
https://cureresearch4type1diabetes.blogspot.com/2023/12/diamyd-update.html
described the main line of DIAGNODE clinical trials designed to get Diamyd FDA approval for people in their honeymoon phase.  You should read that posting for a lot of background material.  In this blog, I'm going to cover two additional clinical trials aimed at expanding the people who can use this treatment and some interesting details about how JDRF is funding this research.

DIAGNODE Expansion Trials

These two trials are using the same DIAGNODE technique (injecting Diamyd into the lymph nodes of people with the HLA DR3-DQ2 gene).  The first is aimed at people who are at-risk of T1D, rather than the honeymooners, which is what previous trials focused on.  The second is aimed at people with LADA, rather than people with the more classic T1D onset, which is (again) what previous trials focused on.

DiaPrecise (Diamyd For At-Risk)

 

This is a small (16 people), trial where half the people get 2 Diamyd injections and the other half get 3, so there is no control group.  Everyone in the study has two autoantibodies, but has not yet been diagnosed with T1D.  Using Trialnet terminology they are in stage 1.

This study is ongoing now and is expected to finish in 2025.

Clinical Trial Registry: https://clinicaltrials.gov/study/NCT05683990

 

GADinLADA (Diamyd For LADA)

This is another small (14 person), phase-II trial done on people with LADA (an autoimmune form of diabetes diagnosed in older people).  People got three injections of Diamyd, one month apart, into lymph nodes.

 

It was successful in the sense that there were no serious side effects, and it is clear that they can do a larger, randomized, blinded study in the future if they wish.  However, I can't evaluate if Diamyd actually helped these people.  They have published C-peptide numbers, which show that the people who got the treatment lost some of their ability to generate C-peptide.  This is not good, but I don't know what happens to people who are not treated, so I cannot tell if the Diamyd helped them or not. 

Journal Article: https://dom-pubs.onlinelibrary.wiley.com/doi/pdf/10.1111/dom.15239

Clinical Trial Registry: https://clinicaltrials.gov/study/NCT04262479 

Money: JDRF, but not T1D Fund

Diamyd (the company) has gotten some money from JDRF through their Industry Partnership Program, and that money is contingent on Diamyd (the treatment) meeting certain successful results.  For me, this is a very interesting development and warrants some discussion.

In the past JDRF operated like most other medical research charities (and the US government) and gave grants to researchers.  The researchers would propose research and if JDRF liked it, they would give the researchers the money to do it.  This is the way most non-profits fund most of their research even to this day.  

However, in 2016 some people active in JDRF became frustrated by the gap between academic research (funded by grants) and commercial research which, for small companies, was funded by venture capital and for large companies, by corporate capital.  So they created The T1D Fund: https://t1dfund.org (especially read the "about" tab).

This fund uses money seeded into it by JDRF and from other sources (mostly wealth investors) to fund commercial medical development work aimed at T1D.  It operates as a venture capital firm.  It makes investments in companies doing work in the T1D space.  As investors they are (generally) part owners of the companies they invest in, and if those companies are successful, they will profit from the success.  Those profits will then be rolled into new investments.

A complete description of how venture capital works (and therefore how the T1D Fund works) is well beyond what I can do in a blog post.  I can't even (quickly) find a good on-line summary that someone else has written!

So as of 2016, there were two separate funding methods for getting T1D products to market: 

• JDRF, traditional grant-based early research focused.
• The T1DFund, venture capital-based and early product development focused.

But now (finally) to the Diamyd point: the funding that Diamyd received is not exactly either of these two funding methods.  It is in between.  The money is coming from JDRF but has some very business like conditions, as described in the bullet point items below.  (These items are taken from a Diamyd press release.)

• Payments from JDRF are earned when Diamyd Medical completes various milestones in the DIAGNODE-3 study, with these milestones spanning the years 2023 - 2027. 
• JDRF can also use its global type 1 diabetes network to raise awareness of the study, which may contribute to patient recruitment, and also provide advisement as Diamyd Medical prepares for a potential commercial approval. 
• If Diamyd Medical in the future gets Diamyd® commercially approved and the sale of the drug becomes a commercial success, JDRF will receive a limited royalty on the revenue, if within the framework of the partnership agreement. 

These are all very business like terms; similar to how one company funds another.  I discuss the details more below, but the summary point is that JDRF is expanding the kinds of funding it can give which adds flexibility to all future investments.  For me, this is a good thing because you never know which kind of investment will benefit a new line of research the most.

Why is all this important?

Most importantly, it means that JDRF will share in the monetary success of Diamyd, if there is any.  This is very different than traditional research grant work, and it addresses a recent frustration.  I know some people were frustrated because JDRF has put money into the academic research with led to the development of Teplizumab, but had not gotten any money out when Teplizumab became a commercial product or even when the company was bought out (for $3 billion US dollars!)  This is perfectly normal in academic grant making, which is traditionally what medical research non-profits have done, but it can leave a bad taste in a donor's mouth.  The Diamyd funding model avoids this.

Also important: Diamyd only gets money when they meet certain milestones.  This is not speculative research grant money;  this is payment on success, motivational money.  It is very common in the world of corporate financing, but I've never before seen it in the world of research grant making.

In another way, I view this as JDRF having more flexibility in funding cures than academic research projects, but not yet self-funding commercial projects. 

Press release: https://www.diamyd.com/docs/pressClips.aspx?ClipID=4676370

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.