Monday, October 9, 2023

DFMO Starts A Phase-II Clinical Trial (TADPOL)

Difluoromethylornithine (DFMO), also known as Eflornithine, is FDA approved since 1990 as an injection to treat African Sleeping Sickness (trypanosomiasis) and since 2000 as a cream to prevent excessive hair growth in women.  DFMO has also been approved, for clinical trial use only, as an oral solution to treat certain cancers. 

I have blogged on a previous Phase-IIº  study for this treatment here:

This drug lowers polyamine synthesis in beta cells.  Polyamines are a class of chemicals used in beta cells to regulate the production of insulin.  The researchers believe that too many polyamines in beta cells that also have inflammation, is part of the process that leads to type-1 diabetes.  They hope that lowering polyamine synthesis will preserve β-cell insulin production and delay the onset of type-1 diabetes.

The New Study

This study will enroll 70 people, aged 6 to 40, who are within 100 days of T1D diagnosis.  They started in March 2023 and hope to finish in December 2027.  The study chair is Emily K Sims, and funding comes from JDRF and Cancer Prevention Pharmaceuticals.

This is a randomized, placebo controlled study.  About 2/3 of the people will get a dose of 1000mg/m2 (see dose note below) because this was the most successful dose from a previous, small study.  This is two pills per day which they will take for 6 months.  There are two primary end points: C-peptide in response to a meal and side effects.  Secondary end points include more C-peptide numbers and measurements of beta cell stress.

If this study is successful at recruiting, it could be finished much more quickly than scheduled.  They only need to gather data for a total of 12 months (6 while taking the drug, and then 6 more).  That means if they can recruit 70 people in 2 years, the study would be done in 3 years, rather than the 4 years they expect, and even faster if they can recruit 70 people in a year.

More information on the study:
Clinical Trial Registry: 

Dose Note

This drug is dosed as mg/m2, meaning milligrams per meter squared.  The dose is based on the skin area of the person getting it.  This is the first time I've seen a drug dosed like that.  I suspect it has to do with the drug's use as a hair growth preventative.


They have already started recruiting in Indiana, and will soon be recruiting at the rest of these sites:

Overall Contacts:
      Maria L Spall     317-278-7034    
      Operations Manager     317-278-8879

Barbara Davis Center, Aurora, Colorado, United States, 80045
Contact: Lexie Chesshir    303-724-1755   
University of Chicago, Chicago, Illinois, United States, 60637
Contact: Triniece Pearson    773-359-7556   
IU Health Riley Hospital for Children, Indianapolis, Indiana, United States, 46202
Contact: Ellie M Ryan    317-278-7037   
Contact: T1D Research    317-278-8879   
Children's Mercy Hospital, Kansas City, Kansas, United States, 64108
Contact: Heather Harding        
University of Michigan, Ann Arbor, Michigan, United States, 48109
Contact: Sheree Nicholson    734-232-4213   
Medical College of Wisconsin, Milwaukee, Wisconsin, United States, 53226
Contact: Joanne Kramer    414-955-8486   

Discussion / Previous Study

The same researcher had previous run a Phase-I clinical trial.  the results of this were published as a poster at IDS 2023.  The key quote on results was: 

An exploratory secondary analysis showed that at the two highest dose levels, treatment with CPP-1X stabilized C-peptide areas under the curve compared to placebo.

However, when I look at the poster results (especially Fig 4A) it looks to me like the placebo group dropped over time (as expected), and the treated group stayed flat.  This does lead to a statistically significant difference at 6 months, but it is not clear to me that it will lead to a cure, treatment, or delay onset, especially when given during the honeymoon when patients are already injecting insulin.  Even if the drug stops loss of beta cells, at that point, the people are already injecting insulin, so I'm not sure it will help much.

On the other hand, for the 1000mg dose group only (the biggest dose given), there is a slight increase in C-peptide generation between 3 and 6 months.  I don't think it is statistically significant, but if we are going to cure T1D, we are going to need to increase C-peptide generation, not just hold it constant in the honeymoon phase.  These are the types of results we are going to need to see, and bigger, in the follow-on study if this line of research is to be successful.

This study also shows the problems we (as a society) face in terms of diversity in clinical trials.  The study involved 41 people.  38 were White, 1 was Black, and 2 are listed as Multiple.   None were listed as Asian, or Hispanic.  They were recruiting in Indianapolis, Buffalo, and Wauwatosa, Wisconsin, and I would think they could do better than that.

Press Release:
The poster itself: 

 More Information:

Discussion / Compassionate Use (Right Now)

In the past, I've often said there were two ways to get access to a drug in the USA.  Either through FDA approval for your illness, or through "off label" use if the drug is approved for a different illness.  However, since 2016, there is a third way, called "Compassionate Use".  This is authorized by the 21st Century Cures Act.  I bring it up here, because Orbus, the company developing DFMO has an official Compassionate Use policy, which you can read here:

It is quite limited, and completely at the discretion of the company to approve.  Patients (and their parents) can not even request Compassionate Use.  Instead, their doctors must request it.  They will need to fill out an FDA form 3926.

I'm sure there are many rules and requirements for this, but the key ones are that the drug is in active clinical development (phase-II or phase-III), and the patient must have a serious or life-threatening disease or condition. 

I expect to see more of this in the future, as companies (and even later, doctors) get more comfortable with this aspect of the 21st Century Cures Act.  I want to stress, that I'm not mentioning it here because I think this particular drug is a good candidate to ask your doctor to ask the company for Compassionate Use.  As I hope I made clear in the "Previous Study" section, the results so far are not so good that they suggest to me that pre-approval treatment with DFMO is worth the uncertainty and risk.  However, I do think it is important for everyone to understand their options before the situation comes up where they might need to use those options.

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 daughter 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.