Results from a Phase-II Trial of Abatacept (Orencia)

Results from a Phase-II Trial of Abatacept (Orencia)

Abatacept is a treatment that prevents T-cells from becoming activated.  Presumably, for type-1 diabetes, it works by blocking the "bad" killer T-cells from activating.  This drug is already approved for use in rheumatoid arthritis when other treatments have failed, and is marketed as Orencia.  It was just recently approved for home use via under skin injections (similar to insulin).  Previously it required an infusion, and this study used the infused form.  It regulates (or modulates) T-cells, rather than depleting them, so the hope is that it will have less side effects than other immunosuppressives.

This study attempts to preserve beta cells during the honeymoon phase by giving newly diagnosed patients Abatacept.  This was a placebo controlled, double blind trial with 112 patients. About 2/3s (77 people) got the treatment and 1/3 (35 people) did not.  Three infusions the first month, and monthly thereafter for two years.  C-peptide production in response to a meal was the measured after two years.  The results where clearly better in the treated group.  Basically they produced 60% more of their own insulin at each point in the trial.  (Remember: C-peptide is a marker for insulin production.)  Also, the treated group had better A1c numbers.  The researchers estimate that this is similar to a 6-9 month delay in beta cell loss of type-1 diabetics at diagnosis.

Since Abatacept blocks some T-cell activation, infection was a worry, but the infection rates were the same in treated and placebo groups, as were injection site issues.  There were more mild side effects (things like headaches and nausea) in the treated group.

The researchers are going to continue to follow the patients to see what happens in the months after they stop getting regular doses of the drug.  They will see if the dosed patients stay ahead of the placebo group or not.

Next Steps

I'm not exactly sure what the next steps are in this line of research.  Are these results "good enough" so that you'd just move the same dosing into phase-III trials and then into the market?   Would you change the dose to try to get a better result?  (It looks like the researchers used the standard rheumatoid arthritis dosing for the trial.)  Would collecting data for a longer period of time, help planning the next move?  Belatacept is a follow on drug to Abatacept which was just approved in June 2011 (but not for type-1 diabetes), so would you move forward with Abatacept,  Belatacept, or both?

Another whole set of options involves combining Abatacept with another treatment.  The study chair for this trial is Dr. Tihamer Orban, who is also working on a B-chain insulin treatment (which already completed a phase-I trial, and which I've blogged on in the past), and he is interested in combining these two approaches. 

Abstract: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60886-6/abstract
News: http://www.medpagetoday.com/MeetingCoverage/ADA/27312
Previous blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/Abatacept
Clinical trial record: http://clinicaltrials.gov/ct2/show/NCT00505375 
More News: http://www.marketwire.com/press-release/new-hope-immune-therapy-children-young-adults-with-type-1-diabetes-founder-orban-biotechs-1546447.htm
Related news: http://www.medicalnewstoday.com/articles/232194.php
Wikipedia: http://en.wikipedia.org/wiki/Abatacept

This study was run by TrialNet.  Thanks to Dr. Tihamer Orban for providing me we a pre-print of the Lancet article.  And thanks to everyone who provided help and information for this posting.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My blog contains a more complete non-conflict of interest statement.
Blog: http://cureresearch4type1diabetes.blogspot.com
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news