If you can still get excited about diabetes research headlines, then here's some exciting news coming out of Cambridge, Mass, this week: Tolerx, a life sciences company, has reported they are in Phase 3 clinical trials for a new treatment of type 1 diabetes. If everything goes to plan, a representative of the company says, Tolerx could launch the first-ever offering approved by the FDA to treat the cause of type 1 diabetes. Pretty cool!
How does it work? Tolerx's research focuses on two types of cells that are critical in the onset of type 1 diabetes. The first are the T effector cells, which direct the immune system when it's attacking invaders like viruses, bacteria, etc. The second are T regulatory cells, which control the appropriate activation or inhibition of T effector cells (in other words, they function to keep the immune responses of the other cells in check).
Obviously, in people with type 1 diabetes, the immune system goes haywire and something triggers the T effector cells to attack the body's islet cells and render them incapable of producing insulin. Tolerx's treatment, with the unpronouncable name Otelixizumab, is an antibody that focuses on manipulating the relationship between the two T cells, by either "down-regulating" the inappropriately activated T effector cells or by "up-regulating" the protective T regulatory cells by targeting receptors on the T cells. Basically, they're telling the T effector cells to chill out, and telling the T regulator cells to get their guys in line to bring things under control. It essentially puts the immune response into remission, preventing progression of the onset of type 1 diabetes.
In the report for the clinical study of Phase 2 studies, published in Diabetologica and conducted by the Juvenile Diabetes Research Foundation (JDRF) Center for Beta Cell Therapy in Diabetes based in Brussels, patients treated with Otelixizumab were found to have preserved function of insulin-producing beta cells in the pancreas compared to patients treated with a placebo — for up to four years after treatment.
At 6, 12, and 18 months, residual beta-cell function was better maintained with Otelixizumab than with a placebo. Of the 80 patients in the study, better outcomes were seen in patients who were younger and had an initial higher baseline residual beta cell function. The study showed preservation of beta cell function, lower A1C levels and reduced glycemic variability.
Now for the bad news: the treatment was associated with a moderate "flu-like" syndrome and some symptoms of Epstein—Barr viral mononucleosis — which is not life-threatening, but definitely no fun — but there were no reported long-term adverse events.
In January, Tolerx completed their enrollment in their Phase 3 clinical study for Otelixizumab called DEFEND-1, and soon there will be a second study, DEFEND-2 which will begin in the next few months. Details of the DEFEND-2 study are still TBD, but you can read some more information (including locations) by visiting their Defend Against Diabetes website.
At present, candidates for the study are defined as people newly diagnosed with type 1 diabetes, within 90 days of their diagnosis. Hopefully they'll have quite a few applicants for this important study — after all, the company states that there are between 30,000 and 35,000 Americans newly diagnosed with type 1 diabetes each year! Using the results from the clinical study, Tolerx will evaluate the overall benefit-risk profile of the new drug.
In case you're wondering if your donations to JDRF are at work here, the answer is yes. Tolerx reports that its studies are funded by a number of sources, including organizations like JDRF. They also receive financing from private investors and a partnership with GlaxoSmithKline.
As far as when Tolerx will actually submit their findings to the FDA, that will be determined by the enrollment of the DEFEND-2 study. So, everything's still TBD. But one thing's for certain — at least we're not talking about mice here!