Primary results from the Immune Tolerance Network’s AbATE study (Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes) were published online today in Diabetes. The Phase II AbATE study, led by Kevan Herold, MD (Yale University), tested two doses of anti-CD3 given one year apart in new onset type 1 diabetics compared to control. After 2 years, the anti-CD3-treated group showed significantly greater preservation of C-peptide compared to the control group (75% higher responses compared to control), meeting the study’s primary endpoint.
A post-hoc analysis revealed that within the treatment arm there were two groups of subjects with different C-peptide trajectories: one group, considered “responders,” showed very little C-peptide decline over the course of the study, while the “non-responders” exhibited a similar rate of C-peptide decline as the control group. The same analysis demonstrated that the “responders” could be distinguished from the “non-responders” by two independent baseline variables: HbAIc and insulin usage. There were also differences in specific T cell subsets between the two groups at baseline, suggesting that immune status might contribute to drug responsiveness.
The ability to identify a subgroup of patients who may be more responsive to therapy could greatly enhance the clinical utility of immune modulators (like anti-CD3) and improve outcomes for those patients. Further analyses with specimens collected from the AbATE study are ongoing to understand the mechanism of response.