Etanercept (ENBREL) Completes a phase-I Trial in New Onset Type 1 Diabetes

This is a "new to me" phase-I study of Etanercept (ENBREL) , which just published it's results last week: http://www.clinicaltrials.gov/ct2/show/NCT00730392 and you can read the abstract of the results here: http://www.ncbi.nlm.nih.gov/pubmed/19366957

This is "give a drug quickly after diagnosis of type-1 diabetes to preserve some beta cell function" type treatment. The drug, Etanercept (ENBREL), is a product of Amgen, who sponsored the research, and is US FDA approved for several self-immunity related conditions including Rheumatoid Arthritis and Psoriasis. You can read more about it here: http://en.wikipedia.org/wiki/Etanercept
Note that although the name is similar, this not Efalizumab which I reported on recently.

The results were solidly good, after 24 weeks:

• HbA1c was lower in the etanercept (5.91 +/- 0.5%) compared to placebo group (6.98 +/- 1.2%)
• The percent change in c-peptide AUC showed a 39% increase in the etanercept group and a 20% decrease in the placebo group
• Insulin dose decreased 18% in the etanercept group compared to 23% increase in the placebo group

So the result in plain English is that the treated patients had, on average, A1C measures 1 lower than the non-treated group. They were generating about 60% more of their own insulin (as measured by c-peptide), and used about 40% less insulin. Overall, very nice results for a phase-I trial.

And before you ask: I don't know if they are planning a phase-II study, and I don't know if this will work on non-honeymooners. I did find two interesting papers that reported that people who had type-2 diabetes and who were treated with Etanercept for rheumatoid arthritis had large drops in their BG numbers. How that maps to people with established type-1 diabetes, I'm not sure. Lastly, although this drug is approved by the US FDA different people may well have different opinions about it's safety. It does carry a black-box warning due to higher rates of infection. (Black-box warnings are the strongest warnings that the US FDA requires on prescription medicines to warn people of potential dangers.)

TNF: Friend or Foe?

This research brings up an interesting conflict in research to cure type-1 diabetes: is TNF a friend or a foe? TNF (tumor necrosis factor) also called TNF-alpha is a protein that kills tumors. It also kills other cells in the body. Several treatments currently in clinical trials for various self-immune diseases are based on interfering with the TNF receptor, and Etanercept is one of these. On the other hand, Faustman holds the opposite theory. Her treatment is based on increasing levels of TNF. The drugs she used on NOD mice (CFA), and in people (BCG) are both expected to raise the level of TNF. Now these two beliefs are not exactly opposite, because Etanercept blocks a TNF receptor, while BCG (and CFA) stimulate the production of TNF itself. However, it is unclear how both Etanercept and BCG can both have a good impact on type-1 diabetes since they effect TNF in opposite ways. If one helps cure type-1 diabetes, the other should make it worse, and visa-versa (at least at first impression). So it is possible to interpret the success of Etanercept as bad news for Faustman. Of course it is also possible that the two work in completely different ways, and TNF is a "red herring" in terms of curing type-1 diabetes.

Here is a link to some discussion of Faustman and TNF:
http://www.faustmanlab.org/docs/mediacoverage/MedPageToday_8-25-08.pdf

Joshua Levy