“Diabetes vaccine” disappoints in pilot study
Autoantigen specific therapy with alum-GAD, an investigational “vaccine” against type 1 diabetes (T1D), did not delay or prevent development of the disease in children aged 4–18 years compared with placebo injections in a small study presented at the ADA 2017 Scientific Sessions in San Diego, California, US.
Alum-GAD contains glutamate decarboxylase (GAD)─an enzyme targeted by autoantibodies in subjects that later develop T1D─formulated with alum. The “vaccine” aims to induce immune-tolerance in subjects at-risk of developing T1D, which is caused by persistent autoimmunity against the insulin-producing beta cells.
After 5 years of follow-up, no study-related or serious adverse events were observed among the participants. Alum-GAD was also not associated with an accelerated progression to diabetes or an increased risk of developing any other autoimmune disease compared with placebo. [ADA 2017, abstract 5-IT-SY07]
However, there was no significant difference between alum-GAD and placebo in delaying or preventing the development of T1D (p=0.573), with a total of 18 children who developed the disease by year 5.
“We could not show that alum-GAD, given alone in the current dosing, delayed or prevented T1D in our cohort,” said study lead investigator Dr Helena Larsson, an associate professor of paediatric endocrinology and diabetes at Lund University in Sweden.
“Since our study shows that alum-GAD treatment is safe, we want to further explore this treatment—either in different doses or in combination with other drugs—in future prevention studies that may impact patient care,” said Larsson. “For example, one option could be to use repeated increasing small doses as is common in classic immune tolerance treatment for allergic symptoms.”
The double-blind randomized study enrolled 50 children (aged 4-18 years) who had yet to develop T1D, but had been tested positive for GAD-antibodies plus at least one additional T1D-associated autoantibody (IA-2Ab, IAA, or ZnT8R/W/QAb). The children were randomized to receive two injections of either placebo or alum-GAD 20 μg, given at days 1 and 30 as a prime-and-boost regimen. They were followed up with intravenous and oral glucose tolerance tests at certain intervals for 5 years. At study enrollment, 26 participants (52 percent) already had impaired glucose tolerance, though none had progressed to T1D.
As the study included both normoglycaemic children and those with impaired glucose tolerance at baseline, the researchers were unable to perform specific subgroups analyses due to the heterogenous rates of T1D progression in the population.
According to Larsson, her team would carry on with the analysis of the immunological samples collected from the patients to understand the mechanistic effects of alum-GAD.
“These results will be important to consider in developing new studies with combination therapies performed,” said Larsson.