Autoantigen GAD vaccine fails to delay, prevent type 1 diabetes in high-risk children

SAN DIEGO — In a small pilot study, treatment with an autoantigen-specific vaccine in children at high risk for developing type 1 diabetes was safe, but did not delay or prevent progression of the disease, according to a speaker here.

In presenting findings from the first prevention study in which an autoantigen-specific therapy was given to children before the onset of type 1 diabetes, Helena Elding Larsson, MD, PhD, associate professor of pediatric endocrinology and diabetes and Lund University in Sweden, said different doses of the vaccine, or combination therapies with other antigens, may be tested in future studies, and that no adverse events or increased risk for other autoimmune diseases were observed during 5 years of follow-up.

“There is currently no treatment delaying or stopping the autoimmune process leading to type 1 diabetes, and children with multiple autoantibodies are at very high risk for developing the disease,” Larsson said during a press conference.

Glutamate decarboxylase (GAD) is an enzyme targeted by autoantibodies in people who go on to develop type 1 diabetes, Larsson said. Previous research with antigen-specific therapies in patients newly diagnosed with type 1 diabetes have shown that injections with GAD may preserve insulin production for 30 months, but later phase 3 studies could not confirm the findings. In DIAPREV-IT, a double blind, randomized, single-center study, researchers assessed the safety and efficacy of alum-formulated GAD65 (GAD-alum; Diamyd, Diamyd Medical) in preventing or delaying type 1 diabetes in children with ongoing persistent beta-cell autoimmunity, as indicated by multiple positive islet cell autoantibodies.

The study is the first with GAD-alum conducted with nondiabetic children, Larsson said.

Researchers analyzed data from 50 children without diabetes at baseline (mean age, 5 years) who had positive GAD antibodies and at least one additional type 1 diabetes-associated autoantibody beginning in April 2009. Researchers randomly assigned children to two 20-µg GAD-alum injections at days 1 and 30 (n = 25) or two injections of placebo (n = 25). Follow-up occurred every 3 months for 5 years. All children underwent an oral glucose tolerance test at baseline; alternating OGTTs or IV glucose tolerance tests were repeated every 6 months. The cohort was followed through January 2017.

Within the cohort, 26 children had impaired glucose tolerance at baseline, Larsson said. During the study, 18 children (36%) developed type 1 diabetes. Researchers observed no between-group differences in the progression of type 1 diabetes.

There were no study-related adverse events or serious adverse events, and researchers did not observe any acceleration of progression to type 1 diabetes or increased risk for other autoimmune diseases.

“However, we could not find a significant effect in delaying or preventing type 1 in the study,” Larsson said.

Due to the small cohort size, there were no subgroup analyses conducted, Larsson said.

“In this first study of antigen-specific therapy with [GAD-alum] in young children ... we found that it is safe, but we could not show that [GAD-alum] given alone in the current dosage delayed or prevented type 1 diabetes in our cohort,” Larsson said. “Other dosing or combination with ... other antigens may be tested in future studies.”

Larsson said researchers collected many immunological samples from the study that still require analysis to better understand the possible mechanistic effects of GAD-alum. – by Regina Schaffer

Reference:

Larsson HE, et al. Session 5-IT-SY07. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego.

Disclosure: Larsson reports receiving research support from Diamyd AB.