Tuesday, June 4, 2024

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


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:

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

Joshua Levy
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.