Wednesday, October 19, 2016

Golimumab / SIMPONI Starts a Phase-II? Trial (T1GER)

Golimumab (sold as Simponi) is an immune system modulator, which has been approved in the United States and many other countries for treatment of several autoimmune diseases, so testing it on type-1 diabetes makes a lot of sense.  It has already been approved to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and ankylosing spondylitis.

The Study

This study will enroll 81 people.  Half will get the treatment, and half will get a placebo, as the study is double blind.  The treatment is a subcutaneous injection once a week.  This is the same kind of injection used for insulin itself.  Everyone will be followed for two years.  The primary data will be C-peptide generation (a marker for natural insulin production), and the secondary data includes A1c, insulin usage, side effects, more C-peptide data, etc.

They started in August 2016 and plan to run until October 2019.

The researchers are planning on recruiting at 30+ different locations throughout the United States. Their clinical trials page says that right now they are only active in Atlanta, Georgia and Lexington, Kentucky. However, I do think they are actively recruiting in Walnut Creek, California as well. (People often forget to update their clinical trial record as they add more sites.)   The contact point for enrollment is this email address:


Golimumab is a monoclonal antibody (meaning it very specifically targets one type of cell). In particular, Golimumab targets TNFα (Tumor Necrosis Factor alpha) an immune signalling protein, which triggers several immune responses, including inflammation.  This is slightly controversial because researchers such as Dr. Faustman are trying to cure type-1 diabetes by increasing the levels of TNFα, while these researchers are trying to cure type-1 diabetes by decreasing the levels of TNFα. This issue came up in 2009, when Embrel (which lowers TNFα) had a mildly successful Phase-I trial. I discussed the "TNFα: Friend or Foe" at that time:

This study is being done by Janssen Research and Development, which is a large pharmaceutical company.

Clinical Trials Registry:
Drug Web Page:
Drug Wikipedia Page:
TNF  Wikipedia Page:

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.


Mike Hoskins said...

Just adding another layer -- This latest research is a byproduct of this initiative launched last yar and reported on in Spring 2015. See this:

Here's what Janssen tells us (at DiabetesMine):

"I am pleased to update you that Janssen Research & Development, LLC, through the DIA and our Immunology group, has initiated a Type 1 Diabetes (T1D) using Golimumab to induce Early Remission (T1GER) study. T1GER is a 104-week Phase 2a placebo-controlled, interventional, U.S.-based study to determine if treatment with subcutaneous SIMPONI (golimumab)* can preserve β-cell function in children and young adults (ages 6-21) with newly-diagnosed T1D. Scientific evidence suggests anti-tumor necrosis factor (TNF)-alpha therapy may present a promising approach to modify and ultimately intercept T1D. This proof-of-concept study will provide efficacy and safety data to better characterize the scientific opportunity, with the aim of advancing a future T1D disease interception strategy.

We believe this study represents an important step in exploring the potential role of TNF-alpha in an autoimmune disease where diagnoses continue to rise 3-5 percent a year globally,i,ii and where individuals contend with life-altering and life-threatening complications, as you well know."

--Brian Kenney, Pharmaceutical Communication & Public Affairs, Janssen Research & Development, LLC

celsus said...

If this innovation were perfectly developed, tested, and available on the market right now I would never, ever take it, given the unacceptably high cancer risk of using these tumor necrosis factor inhibitors. Why is the toxicity of these immunological agents never considered in these assessments by Joshua Levy?!

Joshua Levy said...

I've got three answers to that question:

First, I don't focus on safety because if a drug doesn't work, it doesn't matter how safe it is. So I generally focus on effectiveness first. Especially in the case of Golimumab, which has already been approved for use for other diseases, there is no reason to dive deeply into safety issue until we know if it does anything.

Second, safety is a matter of personal opinion. Different people will look at the same drug, and some will say it is safe, while other will not. You might think Golimumab has an "unacceptably high cancer risk", but someone else might not think it has an extra cancer risk at all, and a third person might think there is a little extra risk, but it is worth it. The FDA requires at least four clinical trials (in most cases) before approving a new drug (and Golimumab is already approved). Some people will say that is enough. Others will want more testing, and still others would be happy with less. No one is right (or wrong) they just have different personal levels of acceptable safety.

I think you're making a serious mistake by thinking that because you don't think it is safe, that everyone agrees with you.

Third, The science does not suggest that TNF inhibitors (TNFi in the quotes below) is a large cancer risk.

For example, this 2012 summary of danger for TNF inhibitors given for rheumatoid arthritis included these results: "the relative risks of cancer among TNFi users were similar and showed no increased risk of malignancy" and later in the paper: "The SIR [Standardized Incidence Ratios] for all cancers among TNFi users and RA in general is not increased."
This review article found that some studies found higher risks of cancers, but that other studies did not, and when all studies were considered together, the overall risk of cancer did not go up.

Another review paper published in 2016 found the same: "these incidence rates of overall cancer, lymphoma and melanoma were not higher in comparison with those patients who were not treated with TNFi." and also "Treatment with TNFi is not associated with increased malignant risks of overall cancer, lymphoma or melanoma."
This paper was very careful to note that people with diseases generally treated with TNFi are at higher rate for some cancers. However, they compared people with a disease who were treated with TNFi to people with the same disease who were not, and found no higher risk of cancer among those who were treated.

The following paper, published in 2013 came to the same conclusions:

I just don't see any evidence that TNF inhibitors are particularly unsafe in terms of future cancer rates.