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!