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!