Alefacept Helps Preserve Function of Insulin-Producing Cells in Type 1 Diabetes

NIH-Funded Study Shows Drug Is Safe, Offers Persistent Clinical Benefit
July 20, 2015
​Results from a clinical trial sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, suggest that the immune-suppressing drug alefacept helps preserve function of insulin-producing beta cells in people with newly diagnosed Type 1 diabetes. In addition, compared to those who received placebo, study participants who received alefacept required less insulin and experienced fewer episodes of hypoglycemia, or low blood sugar, likely because their remaining insulin production helped maintain blood sugar levels within a target range. Importantly, these benefits persisted for more than one year after alefacept therapy ended.
Type 1 diabetes is an autoimmune disease driven by T cells that lead to the destruction of beta cells in the pancreas. People with newly diagnosed Type 1 diabetes retain some beta cell function, providing a window of opportunity for a T-cell-targeted treatment, such as alefacept, to delay or decrease beta cell destruction, which may lead to better glucose control and may reduce the risk of long-term diabetic complications.
In the study, 49 people aged 12 to 35 with new-onset Type 1 diabetes received weekly injections of alefacept or placebo for two three-month periods, with a three-month pause between treatment cycles. Investigators monitored the participants for two years, and noted that alefacept appeared safe, with no serious drug-related side effects in the treatment group.
Although responses varied among individuals, overall the alefacept-treated group showed a smaller decline in insulin production after two years, indicating greater preservation of beta cell function. This group also needed less insulin and had a lower rate of hypoglycemia. Analysis of blood samples from participants revealed that alefacept reduced levels of certain inflammatory T cells but spared protective, regulatory T cells. These findings may help explain some of the clinical benefits of alefacept, but additional work is needed to clarify why some people had stronger responses to the drug than others.
The study was conducted by the NIAID-funded Immune Tolerance Network, and the results are available on the open-access website TrialShare. Additional funding for the work was provided by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Advancing Translational Sciences, both at NIH.
MR Rigby et al. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. Journal of Clinical Investigation DOI: 10.1172/JCI81722 (2015).
James McNamara, M.D., chief of the Autoimmunity and Mucosal Immunity Branch in NIAID's Division of Allergy, Immunology and Transplantation and a co-author of the paper, is available for comment.
Content last reviewed on July 20, 2015