Monday, February 27, 2023

Ixekizumab (Taltz) Starts a Phase-II? Trial In Honeymooners

Ixekizumab, sold under the trade name Taltz, blocks a specific part of the immune system called Interleukin 17 (IL-17).  It has been approved since 2016 in the US and the EU as a treatment for Plaque Psoriasis and Psoriatic Arthritis in people 6 years old or older.  Over 120,000 people have used it.

The researchers believe that Type 1 Diabetes and Psoriasis are similar diseases, and since Ixekizumab has been effective in treating Psoriasis, they hope it will be effective for T1D as well.  This is a quote from their clinical trial registration: 

Psoriasis share several aspects with T1D, e.g. the patchy inflammatory infiltrate consisting of tissue-resident memory (TRM) T cells, leaky blood vessels that facilitate leukocyte migration and the increased risk for systemic conditions. Moreover, interleukin (IL)-17 has shown to be increased in both persons with psoriasis and T1D. Activation of IL-17/IL-22 pathway is viewed to be both a hallmark of psoriasis and human T1D. Ixekizumab, an anti-IL17 biological agent, has shown marked therapeutic value in the treatment of subjects with psoriasis in several randomized trials and is currently an approved clinical therapy. Due to the many similarities in the current view of pathogenesis and manifestation of T1D and psoriasis it is possible that Ixekizumab can also influence the disease process of T1D.

The Study

This study is open to adults (18-35) who are in their honeymoon phase (within 100 days of diagnosis).  They plan to enroll 127 people, and the study will follow them for a year to get primary data, but then continue to follow them for an additional 3 years for extended data.

Patients will get two injections (subcutaneous, much like insulin) the first week, and then one injection every other week for 12 weeks, and then monthly injections for the rest of the year.

The primary end point is C-peptide, which measures how much insulin a person is producing.  Secondary end points include insulin dosage, A1c, time spent in range, and time spent low.  There are 13 other end points being measured as well.

They are recruiting in Sweden at 4 sites right now (Södra Älvsborg Hospital, Sahlgrenska University Hospital, NU-Hospital Group, and Uppsala Academic Hospital), but plan on expanding to 19.  There are two contacts:

  • Marcus Lind, MD, PhD       +46(0)766-183142    marcus.lind@gu.se
  • Shilan Seyed Ahmadi, MD                                    shilan.seyed.ahmadi@vgregion.se   

This study started in November 2022 and they hope to finish in 2027.

Clinical trial registry: https://clinicaltrials.gov/ct2/show/NCT04589325

Discussion

One question that comes up with research on commonly used drugs, like this one, is "T1D is relatively common, so if it helps, and it has been used on so many people, why hasn't anyone noticed?"  There are two answers to this question:

The first answer, at least in the United States, is that there is no central database of medical records, so there is no easy way to see if this is happening, and it is unlikely any doctor would notice in their own patients.  For example, if 120,000 people have used this drug in the world, then maybe 40,000 of them are in the US.  If about 1 in 400 people in the US have T1D, then this drug has been used on about 100 people with T1D.  

For an individual doctor, they are unlikely to have more than 1 patient who has T1D and is taking this medicine, so unless the results are really extreme, the doctor will see it as just the natural variability of the disease.  They are unlikely to see a pattern, because they are unlikely to have even 2 patients in the same situation.  After all, there are only about 100 such patients in the whole of the US. 

However, there is no way to get get medical data on these 100 people, not even anonymously, and there is no way to even find out which 100 people it is.  Some European countries do have these kinds of medical record databases, and they sometimes do publish this kind of research.  However, their populations are much smaller, so the number of people reported on would be smaller as well. 

In the last few years, we have moved, slowly, toward better medical record databases.  For example, I have seen studies based on Kaiser's medical record database.  Kaiser is unusual in that it is both an insurance company and a medical provider with its own hospitals, clinical, and staff.  Therefore, it has the medical records, the motivation for improvement, the infrastructure, and the large scale, needed for this kind of record based research.  

The second answer is that this is not likely to be a sudden cure at the standard dosage.  Because that would, indeed, be too obvious.  If people took the standard dose and were suddenly cured, even just once, some doctors would notice.  However, it still may be true that this helps T1D, that it encourages insulin production, and can lead to a cure in a different dosage than currently given.  


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
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.

 

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