A Phase-I Trial of DFMO is Fully Enrolled
Alpha Difluoromethylornithine (DFMO) is approved for two quite different issues. The first is to remove/prevent facial hair in women, while the second is to treat sleeping sickness. Neither of these are related to type-1 diabetes. However, this drug was effective in preventing diabetes in NOD mice (which are predisposed to an autoimmune diabetes, similar to human type-1 diabetes), when given to these mice before they developed T1D. That is what motivated this trial.
This trial finished enrolling new patients in Oct-2019. Once a trial is fully enrolled, everyone knows when it will end, or at least when they will finish gathering the required data. So in a very real sense, we can see the end of the tunnel now. This trial will collect data for 6 months, so the data should be collected by April-2020, and (hopefully) will be published soon. However, with COVID-19, nothing is certain. My policy is to wait two years for a publication. In fact, my experience is that successful studies are usually published in less than a year. So from a practical point of view: if it is not out in a year, it is not likely to be successful.
Previous Blogging: https://cureresearch4type1diabetes.blogspot.com/2018/06/alpha-difluoromethylornithine-dfmo.html
Clinical Registration: https://clinicaltrials.gov/ct2/show/NCT02384889
Unsuccessful Results for a Phase-II? Trial of GNbAC1
While this trial was underway, the treatment got a new and improved name. It is now called Temelimab. Do not mix this drug up with Teplizumab or Tocilizumab. All three of these drugs are different.
GNbAC1 is a monoclonal antibody which was developed by GeNeuro SA and has completed phase-II testing for treating Multiple Sclerosis, which (like type-1) is an autoimmune disease. This phase-II? trial finished in May-2019, but unfortunately was not successful. The key sentence in the results section was this:
Concerning exploratory endpoints, there was no difference in the levels of C‐peptide, insulin use or HbA1c between treatment groups ...Results: https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.14010
Previous Blogging: https://cureresearch4type1diabetes.blogspot.com/2018/06/gnbac1-starts-phase-ii-trial.html
Clinical Registration: https://clinicaltrials.gov/ct2/show/NCT03179423
Notes on Understanding Research Conclusions
Here is the entire Conclusions section for the results of the GNbAC1 study together with how I interpret them:
Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti‐insulin antibodies) under temelimab were observed. Markers of β‐cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.Although if read quickly this sounds positive, it is (in fact) reporting on a failure. So let me break it down into what each sentence actually means:
Temelimab appeared safe in patients with T1D.Paradoxically, this is bad news when it is the first sentence in the conclusions. Almost all T1D studies get information on both effectiveness and safety. Because effectiveness is the more important information, if they lead with safety results, then that means the effectiveness results were not good. For a successful study, one that gets us closer to a cure, a sentence about safety will be farther back in the conclusion section.
Pharmacodynamics signals (hypoglycaemia and anti‐insulin antibodies) under temelimab were observed.These results are not critical for curing T1D, especially when you remember the key result (no difference in C‐peptide, insulin use or HbA1c). This is just reporting on what tiny crumbs of good news they could find at the bottom of their research data. "Signals" usually means small (ie. not statistically significant) changes. It sounds like the patients had slightly fewer low BG episodes and slightly fewer anti-insulin antibodies.
Markers of β‐cell functions were not modified by treatment.This is the most important result, because beta cell function means insulin production, but this did not change. This is what matters in terms of a future cure.
These results need to be further explored in younger patients with T1D with earlier disease onset.Normally, calls for more research should be ignored, because any research can be followed up with more research. It is meaningless for a researcher to call for more research, because they always do this. However, this sentence is more negative than most, because it says that the research should be done on different people than this study, which implies that more studies on these people would not be useful. And, to make things worse, none of the conclusions suggest that this other group of people would have better results.
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.