Friday, May 16, 2025

Diamyd’s GABA-Based Remygen® Unsuccessful in Phase 1 Clinical Trial

This clinical trial tested whether long-term daily treatment with Remygen®, an oral drug developed by Diamyd Medical, could help restore insulin production in adults with longstanding type 1 diabetes (T1D). The active component of Remygen® is GABA (gamma-aminobutyric acid), a compound that in earlier experimental studies appeared to support the regeneration of insulin-producing beta cells, improve insulin release, and reduce inflammation.

What Was the Clinical Trial Testing?

The trial enrolled 35 adult men with T1D for at least five years and divided them into three treatment groups. One group received a lower daily dose of GABA, a second received a higher dose, and a third group received the higher GABA dose plus a short-term course of alprazolam (an anti-anxiety, benzodiazepine drug). The treatment lasted six months.

Researchers monitored insulin production using fasting and post-meal C-peptide levels, tracked blood glucose control, and recorded any side effects or adverse events. The goal was to assess both the safety of long-term GABA use and whether it had any regenerative effect on the pancreas.

What Were the Results of the Clinical Trial?

The trial found that Remygen® did not restore insulin production or improve any markers of beta-cell function.

C-peptide levels, which reflect the body’s natural insulin production, remained unchanged in all treatment groups throughout the six-month period. This included individuals who had some detectable C-peptide at baseline, as well as those with undetectable levels. No meaningful changes were observed for insulin production either.

Measures of blood sugar control—including continuous glucose monitoring data and HbA1c—also remained stable, with no significant improvements seen in any group.

Additionally, the trial found no change in the body’s hormonal response to low blood sugar. This was in contrast to some earlier short-term studies that had hinted at possible effects of GABA in this area.

In terms of safety, the treatment was generally well tolerated, but side effects were common.  One participant had a serious liver reaction, likely related to the drug, though liver function returned to normal after stopping the medication.

Discussion

My memory is that, at its height, there were 4 or so GABA related clinical trials running.  But this was the last GABA clinical trial that I knew of, so I think this line of research is dead for now.

Diamyd has also been developing a DNA-based immunotherapy (also called Diamyd®) aimed at slowing or stopping the immune system’s attack on beta cells, a different strategy from GABA. That program remains in clinical development. 

EU Clinical Trial Registry: 2018-001115-73

Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions.  I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs.  I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately.  My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here.  I am obese and right on the boarder of T2D and therefore may be taking drugs for those conditions.  My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Thursday, May 8, 2025

Changes to My Blogging: AI

I'm going to start using generative AI (what people call "chatbot" technology) to help me create draft blog postings.    In all cases, I will review and edit every word to ensure three things:
  • Every posting has the right tone.
  • Every piece of information in the posting is accurate.
  • Every posting conveys the truth, as I understand it, in terms of importance, future directions, risks, unknowns, and so on.  I check that the things implied the posting implies are true, are in fact, true.
This blog has never accepted as sufficient mere facts-and-figures accuracy (what the media often calls "fact checking").  In addition to checking facts, I have always spent a lot of time checking that the tone, implications and views conveyed in this blog are also the truth, as far as I know it.  That will continue, even as I use AI to help write initial drafts of the blog.

I'm starting to use AI for three related reasons:  First, blogs take a lot of time and I hope that using generative AI will allow me to create blogs of the same quality in less time.  I'm not going to save time in the editing or reviewing part of writing blogs, but crafting the English takes me a lot of time and I hope AI can speed the process. Second, I hope that I can use this newly available time to either create more blogs or create more complex blogs.   I want to do more analysis and historical perspective type blogs, rather than just writing all the time to keep up with the clinical trial results.  I feel that is sort of the news equivalent of "treading water", and what I want is to get ahead of the news and use the news to write more inciteful posts.  Third, it would be nice to get news about clinical trials out quicker so you can read about it sooner after the results are announced.

In terms of "how will I use AI", I'm not going to use it in a simple minded or unthinking way! I am going to experiment with several different methods and expect to end up using a combination of these techniques, and incrementally improving them over time.  
  • For example, one simple technique would be to have many different chatbots respond to the same question, and then I, as a human, merge the best parts (or the best language) from each of their responses together to create a posting.   
  • Another technique I will try is asking very specific, very focused questions of AI in order to generate parts of the blog posting.  Then (as a human) merging those parts together into a posting.
  • I will also experiment with creating very complex detailed questions for the AI in order to generate blog postings all at once.  (This is called "prompt engineering".)
The future is the undiscovered territory, and I am going exploring.


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions.  I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs.  I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately.  My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here.  I am obese and right on the boarder of T2D and therefore may be taking drugs for those conditions.  My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Thursday, April 24, 2025

Sana Biotechnology Reports First Results For Islet Transplants Without Immunosuppression

This blog post reports on some news that I consider exciting, for at least two different reasons: first because it might be an early milestone on a path that leads to a practical cure of established T1D.  The second because it could speed up research into similar cures.  However, it is important to understand what is actually new and unique about this news, and how it differs from previous news that sounds similar.




Background: Islet Transplants Without Immunosuppression

At least 50 years ago, it was pretty clear that the beta cells of people with T1D were destroyed, and that gave hope that transplanting in new beta cells might cure T1D in a straightforward way.  It did not happen, because the new cells were attacked by the body's immune system for two reasons: (a) they were foreign cells so the immune system attacked them "normally", as part of the healthy attack on foreign cells.  And (b) because the immune system is broken, leading to T1D in the first place, it attacked these new cells "abnormally" just as they had attacked the body's own cells to trigger T1D in the first place.

One way to solve both these problems is to modify the new cells so that they are invisible to the immune system.  That is, they don't present as foreign cells nor do they present as beta cells.  This is the solution that Sana Biotechnology has been researching, and that I'm reporting on here.

What Was Reported

In a very small clinical trial, they reported data on the first person transplanted with beta cells, after one month:
  • C-peptide data shows the transplanted beta cells were generating insulin, and were generating it in response to eating carbohydrates.  
  • MRI images suggest that the new beta cells are surviving.
  • No safety issues were seen.
  • The new cells appear to have avoided any immune attack ("evaded immune responses"). 
This is all good news, but notice what was not reported: no specific numbers on C-peptide generation, which means no specific numbers on insulin generation.  And similarly, no numbers on insulin usage, A1c, or anything else to show how well the new beta cells were operating.

Also notice the limitations of this reporting: one person and one month, and no scientific journal article, just a press release.

More Study Details

The entire study is a two person, phase-I study lasting a year, so not much bigger.   Donated beta cells are modified using Sana’s Hypoimmune (HIP) technology, and then implanted into the forearm of the person with T1D.   The procedure took 90 minutes.  The HIP technology is the "secret sauce" that Sana hopes will make the cells invisible to the immune system.  This protocol is identified as "UP421" and they are using it in another program aimed at cancer. 

This study was very much a proof of concept.  The researchers are implanting between 2% and 7% of the beta cells that will ultimately be needed, to see if they get any results at all.  They are measuring C-peptides, as well as various safety and immune system measurements.  But the summary is, even when the whole clinical trial is done, we will have very little information.  


Last Minute Update

Just as this blog was going out, Sana released a corporate presentation, which had some additional information.  The main updates are as follows, and I think they are all very positive:
  • Three months of data are included, and the c-peptide numbers continue to be strong for the entire time.
  • They include data (specific numbers) for fasting and mixed meal c-peptide data.  Considering how small the transplantation was, the results are very promising.
  • They include immunology data that supports their claims that the newly transplanted beta cells are not triggering an autoimmune response.  

Discussion

What To Look For In The Future (and When)

To me, this has the potential to be a huge breakthrough, as it could lead to a practical cure in the future.  The key words here are "potential" and "future".  For many people the next questions is, how likely is it or how long will it take.  But those are not my questions.  My questions are, what are the next reports we should expect to see, and what data from those reports will signal good news?

Unfortunately, we are not going to get a lot more information any time soon.  This data comes from a very small, phase-I clinical trial: only two people in total (both treated, no control group). That means that over the next year, the very best we can hope for is 2 people; no control group; a small dose; all published in a scientific journal.  That is not much (although one year is not long to wait).

The next data we should expect, would be the results of a phase-II or maybe a phase-II/III clinical trial.  But we should not expect that for 3 or 4 years.  And remember, no matter how successful the current  study is, and how successful the next study is, approval will still require an additional phase-III study (maybe two phase-III studies), which is more years.


Is it a cure?  The immune system is still broken!  

One comment I sometimes hear when I talk about transplants is that they are not cures, because the immune system is still broken.  They might stop the symptoms, but they do not cure the "real" disease, the flaw with the immune system.

This gets into the very emotional question of what is a cure.  After all, if someone's leg is crushed and you install a pin, have you cured them?  What if the pin means they can walk but not run?  On the other hand, if they crush a leg, and need a wheelchair for the rest of their lives, are they cured?  After all, the wheelchair means they can get around.  And so on.

My answer to this question is on my web page, just to the right of every blog posting I write: 
1. Blood sugar control without testing and with doctor's visits four times a year, or less. Any cure must result in an average lifespan close to normal.  
2. Does not require a lifetime of immunsuppressive drugs, so it is not trading one treatment for another. (but a couple of operations, or a short course of drugs is OK) 

 Obviously, this is my personal definition of a cure; yours may differ.

By that definition, this would be a cure, if it works.  The fact that the immune system is still broken does not change the fact that the person no longer needs to take insulin, count carbs, or wear a pump 24x7.

History and Complexities of Islet Transplants

You don't need to read this section to understand the research, or why it is important.  I'm putting it here for people who find it interesting.

The history and complexities of islet transplant research is a huge topic, far to big to fit in one blog posting, much less one section of a blog posting.  However, I will try to summarize both the history of transplant-based cures and the complexities that have prevented the research from succeeding:

Transplant History

In the 1970s and 1980s, it was commonly thought that type-1 diabetic's beta cells had been destroyed, and if they could just be replaced, their diabetes would be cured. This led to several attempts at transplants to cure T1D, especially whole pancreas transplants, beta cell transplants, and drug treatments designed to get beta cells to regrow (such as human growth hormone). 

These did not work because the new beta cells were destroyed by the broken immune system just as the old ones had been, and also because the properly working immune system attacked transplants as foreign cells.  

Starting in the 1980s, researchers tried encapsulating beta cells: they put beta cells inside a wrapper and then implanted the bundle in a person. The wrapper would need to be a very high-tech material that would allow nutrients and oxygen to flow in, wastes to flow out, insulin to flow out, and the chemicals which triggered insulin production to flow in. But if they succeeded, it would be like having a natural pancreas inside you, but protected from the immune system.

Many different companies and many different researchers tried to use encapsulated beta cells to cure T1D.  There were a lot of different options to try.  Every researcher needs to choose a source of beta cells, and an encapsulation technology.  Optionally, they might also add an unusual transplant location or a new drug protocol for the transplant itself.  Since there are many different sources of beta cells, and an almost unlimited number of encapsulation technologies, you can see how this would keep many researchers busy for many decades.

At different times, beta cells have been sourced from: pigs, genetically modified pigs, human cadavers, or live humans.  Plus, they have been grown from stem cells sourced from: the person with T1D themselves, other people's skin cells, placenta cells, or embryos.  Plus, I'm probably forgetting a few, since this research has been going on for 40 years!

As for encapsulation technologies, there are dozens of them, and I'm not even going to try to list them, but all kinds of modern material science has been applied to the problem.

However, to date nothing has worked.  I believe that there are several problems and solving one tends to make the others worse, and it is very hard (so far, impossible) to solve all of them at once.  The problems include: 
  1. Allowing nutrients to pass from the body into the new beta cells, and waste products to pass from the beta cells back out to the body.
  2. Not allowing immune cells to move from the body to the beta cells.
  3. Allowing sugar to pass in and insulin to pass out.
  4. Not having the body build up scar tissue around the beta cells, which blocks access to them.
You'll notice that solutions to problems 1 and 3 tend to make problem 2 worse, while solutions to problems 2 and 4, tend to make problems 1 and 3 worse.  Of course, all problems must be solved at the same time, for this to work.

Sana's Approach Is Different

Sana Biotechnology is not trying to encapsulate beta cells.  Instead, Sana is trying to alter them so that the immune system can not detect them.  This would solve both major transplant problems at once.  The "natural" attack on any foreign cells would not even see the new cells, and the "broken" attack on beta cells would not even see the beta cells to attack them.

The immune system identifies cells by identifying specific structures on the outside of cells.  MHC Class I and II are two such structures and the CD-numbers refer to other such structures.  So Sana is trying to remove these structures from the outside of their beta cells.  The hope is that then the immune system will not see the cells at all.

I'm not a researcher, so I have a lot of trouble evaluating the science behind Sana’s Hypoimmune (HIP) technology.  However, here are two summaries of HIP that I could find:

Sana's approach seeks to modify cells to evade both innate and adaptive immune responses by knocking out MHC Class I and II expression and over-expression of CD47.

The goal of Sana’s hypoimmune (HIP) platform is to eliminate the need for immunosuppression by cloaking cells from immune recognition while at the same time generating the manufacturing scale and reproductibility of allogeneic cells. The challenge for the field to date in generating immune cloaked cells has been turning off both the adaptive and innate immune system concurrently. Sana’s platform includes disruption of major histocompatibility (MHC) class I and MHC class II expression to hide cells from the adaptive immune system, which includes antibody and T cell responses, as well as overexpression of CD47 to inhibit activation of the innate immune cell system, in particular macrophages and natural killer (NK) cells. 

As with all research approaches, it doesn't matter if it sound good or if it makes sense.  It only matters if it works in clinical 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 BreakthroughT1D or JDCA news, views, policies or opinions. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here.  I am obese and right on the boarder of T2D and therefore may be taking drugs for those conditions.  My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Tuesday, March 18, 2025

TIXIMED Starts a Phase 1 Study of TIX100


TIX100 is a protein which inhibits the action of TIXNP (thioredoxin-interacting protein).  It is being developed by the TIXIMED company.  TXNIP is elevated in pancreatic islets of people with type-1 diabetes and causes beta cell death and dysfunction.  The hope is that inhibiting that protein will protect beta cells and therefore delay or prevent T1D.

Anath Shalev, a researcher at the University of Alabama, Birmingham is leading this research effort, first at UAB and now also at TIXIMED.  She first identified TXNIP in 2002 in human islets exposed to high glucose and then later showed that it played a role in glucose toxicity and diabetic beta cell loss.  Research has shown that inhibiting TXNIP protects beta cells and promotes beta cell health and function.

Recently she has run clinical trials for Verapamil, which lowers TXNIP and is already approved in the USA for the treatment of high blood pressure, migraines, and heart problems.  I have blogged several times on those studies, but especially the results from a phase-II trial here:
I also listed it as a drug to watch in 2024:
because there is another phase-II study ongoing in Europe, but it is now scheduled to finish in 2025 or 2026.

TIX100 is an oral medicine, and a "small molecule", but I have not found any other public information on what it actually is.  It has been tested in animals for T1D, T2D, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).  For example: 
https://diabetesjournals.org/diabetes/article/72/Supplement_1/97-OR/150782/97-OR-Antidiabetic-TIX100-Improves-NAFLD-NASH-in

This Study

This is a blinded dosing study done in healthy people.  They are recruiting 35 people, none of whom have T1D, and giving them 6 different doses ranging from none to 200 mg of TIX100.   The goal is to make sure all potential doses are safe.  

This is a single dose study, follow up is after one week, and they expect to be done by May.  Because the end points are all safety and side effect related, we will not know anything about efficiency (if it actually works against T1D), but "the trip of 1000 miles starts with a single step".  Good results here will presumably enable an efficiency focused phase-II study.

The good things about this study are that it is quick and easy to participate in.  They are recruiting in one location:

Chula Vista, California, United States, 91911
ProSciento, Inc.  619-427-1300   hello@myproscientostudy.com

Corporate Web Page: https://tiximed.com/

To see a longer history of research into curing type-1 diabetes by targeting TIXNP, you can read this article: https://www.news-medical.net/news/20240731/FDA-clears-UAB-startups-TIX100-for-clinical-trials.aspx




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!

Friday, March 7, 2025

Combination of Harmine and GLP-1RA Completes Phase-I Clinical Trial (In Healthy People)

This is the most fun I have had writing a blog in a long time.  It is not often I can blog about psychedelics and curing type-1 diabetes at the same time!  I hope it is as fun for you to read as it is for me to write.  Do not skip the "Discussion" section.

These researchers are testing Harmine as part of a long term project, which started by doing a quick screen of many chemicals, which identified Harmine as a possible way to help the body grow more beta cells.  This screening process involved cell cultures (i.e. biology not computer simulation). They then tested it in mice, and found strong beta cell growth.  They cured the mice of diabetes, but those mice did not have autoimmune diabetes.  Their pancreases were destroyed with a toxin to give them diabetes.  A different research group cured mice who were overfed into diabetes. These are both positive results, but neither involved autoimmune diabetes.

You can read about the mice research here:

This blog reports on their first test in people, but they did not have T1D.  The researchers hope to move on to people with T1D in the future.
  

The Study


This study is unusual in that it enrolled people without T1D ("healthy people", in medical terminology) and only looked for bad side effects ("adverse effects") in the medicine and not effectiveness.  Almost all T1D studies that I've blogged about over more than 10 years, even the earliest phase-I trials enroll people with T1D and have end points that cover both safety and effectiveness.  But not this study.

This is an open-label, no control group, dose escalation study which enrolled 27 people.   Each person goes through the following doses: 100 mg, 200 mg, 300 mg, 500 mg, 700 mg, 900 mg and 1200 mg, stopping when they experience side effects.  The researchers are trying to find the largest does that has minimal side effects.

The results are summarized like this:  Harmine HCl can be orally administered to healthy participants in doses <2.7 mg/kg with minimal or no adverse effects. Doses >2.7 mg/kg are associated with vomiting, drowsiness, and limited psychoactivity.   So a 50kg person (110 lb.) can have a dose of 135 mg with minimal adverse effects, and a 91kg / 200 lb. person can go up to 270 mg.

This is good news, because it opens the way for clinical trials on people who have T1D, and tells the researchers what is the maximum dose they can use without bad side effects.


Discussion


Dose Comparison to Mice Work


The important finding of this clinical trial is that doses less than 2.7 mg/kg are safe and well tolerated.  ("well tolerated" being medical jargon for "In our judgement, the side effects of this treatment are small enough so that people would be willing to get them in order to also get the benefits of the treatment".)  For comparison, two previous research projects targeted curing T2D in mice with 30 mg/kg and targeted T1D mice with 3 mg/kg.  Together, this trial in people with T1D and the previous trial in mice suggests that the 3 mg/kg is a "sweet spot" dose: high enough to work and low enough to avoid bad side effects.

However, there was another difference.  People in this study were given Harmine in a single pill, but the previous mice study gave Harmine using a subcutaneous pump (like an insulin pump) and continually dosed throughout the day.  For comparison, the T2D mice were given 30 mg/kg daily with an injection.  So if we compare the people to the T1D mice, they got a similar dose, but the people got it once in a pill and the mice got it infused daily for months.  Since pills are generally easier to take than injections, this is good news, if pills are as effective as injections.

Obviously, an important target of future research is going to be if pills are an effective way of delivering this medicine, or if a continuously dosing pump is required.


Psychedelics


Harmine is found in several species of plants (esp. wild Rue) and animals (esp. butterflies), but it is famous as a component of Ayahuasca, a South American psychoactive folk medicine and religious sacrament.

It is being tested for psychiatric uses (suicide prevention, treating depression, PTSD, etc.) in several clinical trials, some of which have completed and some of which are ongoing.  

My favorite quote is from one of the researchers: 
no psychoactive properties have been identified in animal studies at the doses we are employing, but animals can’t tell you if they’re hallucinating

Obviously, this is why they are carefully doing a phase-I trial on healthy humans, looking specifically for psychedelic adverse effects.  I suspect it is also the reason the study was done at the Depression and Anxiety Center at Mount Sinai Hospital in New York city.  They have more experience with this kind of clinical trial.

I'm sure the association of Harmine with Ayahuasca is going to cause some regulatory complications, even after this study shows that it is not psychoactive at the doses they are giving.  The American DEA has a long history of aggressively opposing any potential medical use associated with psychoactive drugs.  

Wikipedia article on Harmine: https://en.wikipedia.org/wiki/Harmine
Wikipedia article on Ayahuasca: https://en.wikipedia.org/wiki/Ayahuasca

What Next?


In my mind, the obvious next step is to run a phase-I or phase-II trial on people who actually have T1D, but that is not the direction these researchers are going in.  As described below they are looking for a patentable drug (which they hope will be even more effective).

And then there is the issue of bringing these discoveries to people with diabetes. Because harmine is a natural product, it can’t be patented. “If you can’t patent it, no drug company is going to make it because clinical trials are expensive,” he notes.

So, going forward, the team has turned its efforts toward other new small molecule compounds they have designed and synthesized, along with computer modeling. “Some of these are as good as harmine, and several are substantially better. Mount Sinai has patented these, and we’re now working to move them along via Mount Sinai’s Innovation Partners Program,” Dr. Stewart says.

These two paragraphs come from this article:

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.  I am obese and right on the boarder of T2D and therefore may be taking drugs for those conditions.  My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Friday, January 31, 2025

Denosumab Starts A Phase-I Trial In People With Established T1D

Denosumab is a monoclonal antibody, which is already approved for several bone related diseases and is sold under the names Wyost, Xgeva, Prolia, and Jubbonti.  A research team has found that the pathway that Denosumab targets also has effects on beta cells. Animal studies suggest that Denosumab may protect and/or increase the number of beta cells and improve how well they work.  It was first approved in 2010 after being developed by Amgen.  There is a biosimilar available from Sandoz.

Denosumab is a subcutaneous (under the skin) injection, much like insulin.  It is taken every month or every six months, depending on the bone disease being treated.

This Study

This is a phase-I trial in 45 adults who have had T1D for between 1 and 5 years. It is blinded, randomized and has a control group.  People will get one injection every 3 months for one year.

There are two primary end points.  For safety, they will track adverse events and for effectiveness they will measure C-Peptide levels. There are secondary end points for more C-Peptide measures and also for A1c measurements.  There are tertiary end points for time-in-range and insulin sensitivity.

The trial started in September 2024 and should run until April 2026.

This study is funded by JDRF and is run out of City Of Hope.  Contact information is:

Name: Arthur Riggs Diabetes & Metabolism Research Institute at COH
Phone: 1-866-44-ISLET(1-866-444-7538)  
Email: Islets@coh.org

And the three sites recruiting are:

University of Alabama-Birmingham Comprehensive Cancer Center
Anath Shalev, MD
205-996-4777 ashalev@uabmc.edu

City of Hope Medical Center, Duarte, California, United States, 91010
Fouad Kandeel, MD, PhD
866-444-7538 Islets@coh.org

Indiana Univ Med Ctr, Indianapolis, Indiana, United States, 46202
Carmella Evans-Molina, MD
317-278-3177 cevansmo@iu.edu

Discussion

This study is being done on people with established T1D, not honeymooners.  However, I'm not sure why.  The researchers state specifically that "Lab studies suggest that Denosumab may protect and/or increase the number of beta cells and improve how well they work."  For me, that suggests that this treatment would work much better during the honeymoon, when people with T1D still have some beta cells that work.  It is a mystery to me why they chose established T1Ds rather than honeymooners.

One large population based study, done in Taiwan, showed that people using Denosumab for Osteoporosis had a significantly smaller chance of being diagnosed with type-2 diabetes, than those who where not taking the drug.  That is an interesting finding, but those people all had plenty of working beta cells, so it is not clear to me that this finding is useful for people with established type-1 diabetes.  That study is published here: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814873

If this treatment is found effective, it could be used off label immediately, without FDA approval, since it is already approved for a different disease.

Clinical Trial Registry: https://www.clinicaltrials.gov/study/NCT06524960 
Denosumab: https://medlineplus.gov/druginfo/meds/a610023.html


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!

Sunday, January 19, 2025

What To Watch In 2025

Last year, at the start of the year, I published a blog of four research projects I was looking forward to updates in the new year.  This year, I'm doing the same thing.  I'm also including an update of the project from last year.

What I'm Watching In 2025

Vertex VX-264 is an encapsulated beta cell transplant that does not require immune suppression.  The trial is expected to run until 2026, but the company has said that they expect to have some data to report in 2025.  I hope so!


VCTX211 is another encapsulated beta cell transplant that does not require immune suppression.

Biomea BMF-219 is a drug that the company hopes is "a brake on beta-cell turnover and growth, supporting the notion that [it] could lead to the regeneration of normal, healthy beta cells".  It is in the middle of a clinical trial which started in 2023 and is expected to finish in Sept-2025.  I'm looking forward to data in 2025.  I previously blogged on it here:


Ladarixin is a drug being developed by Dompé. It inhibits activity on parts of the immune system called the IL-8 receptor (which has two subtypes: IL-8a and IL-8b).  Dompé hopes that this will stop the progression of type-1 diabetes.  Ladarixin is in the middle of a phase-III trial, and they expect results in 2025.  This is a big study.  They have enrolled 327 people and 2/3s of them will get the treatment; with only 1/3 controls who get the placebo.


Siplizumab is a monoclonal antibody targeting CD2, which is part of the immune system.  This study finished recruiting in Oct-2024, so I would expect results in late 2025.  I blogged on this here:


Sana UP421 is a last minute addition.  It is a no-immunosuppression beta cell transplant.  In early January, they announced very positive 1 month data from 1 person.  They are currently running a 2 person study (so really tiny pilot study).  I'm not sure if they will have final data in 2025 or not, but if they continue to publish early data, I'll be following.

https://www.clinicaltrials.gov/study/NCT06239636

What I Watched In 2024

The quick summary of 2024, is that, of the four research projects I focused on:
    1. Semaglutide is big in T2D/Obesity, but did not make progress as a T1D cure.
    2. Ladarixin progressed as expected, but the real news is expected in 2025.
    3. Verapamil completed enrollment in 2024, so should have results by 2025, but has already led 
        to important follow-on work.
    4. Diamyd was hoping for full enrollment, but did not make that milestone.
So overall, I would say 1 project did better than expected, 1 project did as expected, and 2 projects did worse.  

Semaglutide (sold as: Ozempic, Wegovy and Rybelsus) had very strong results in a very small study of honeymoon T1Ds:

I was hoping to read about more research starting up in 2024 to confirm these results.  Because Semaglutide is widely used to treat T2D and for weight loss, I think just one or two confirmation studies will be required to enable widespread use.  If that gets us a year or two delay starting injections for newly onset T1D, that would be a huge win (and even more so if it could be combined with Teplizumab or other treatments).

Unfortunately, none of that happened.  Semaglutide continues to blow up (in a good way) for T2D/Obesity, but does not move forward for T1D.

Ladarixin is a drug being developed by Dompé.  I'm not sure why I put it in the 2024 list, because there was no expectation of results until the end of 2025.  Nothing happened, but it is on my 2025 list.


Verapamil is another interesting "off label" drug.  This is a drug which is already approved (since 1981) and widely used (3 million prescriptions a year) for high blood pressure.  It is being tested on honeymooners.  Therefore, if clinical trials show that it helps, it should be available quickly, especially for aggressive doctors who are willing to prescribe it off label.

Unfortunately, the ongoing study which was going to finish in 2024 is now going to finish in either 2025 or 2026, so we'll be waiting longer for results.  I blogged about the start of this study here:

However this line of research has already led to the creation of the company TIXIMED working to start clinical trials on their drug TIX100, which is sort of a follow on to Verapamil.  They have gotten FDA approval for the clinical trial, but have not yet started it.

Diamyd is another drug in phase-III trials.  They hope to finish in 2025, but the news I was hoping for was that their clinical trial was fully enrolled in 2024.  Unfortunately, it looks like that did not happen.  The trial is still not fully enrolled, so I would not expect results in 2025.



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.