Translational research, led by scientists at the La Jolla Institute of Immunology (LJI), has resulted in a promising compound therapeutic candidate for adults with recent type 1 diabetes.
The combination therapy was recently tested in a randomized, double-blind, placebo-controlled phase 2 test and funded by the pharmaceutical company Novo Nordisk. The results, recently published in The Lancet Diabetes and Endocrinology, point to a possible way to treat the autoimmune disease without making the body susceptible to infectious diseases.
The therapeutic candidate combines an anti-IL-21 antibody with the diabetes drug liraglutide. This two-pronged approach is based on research from the laboratory of LJI Professor Matthias von Herrath, MD, who also serves as Vice President and Senior Medical Officer of the Global Chief Medical Office at Novo Nordisk.
This is the first large study for combination therapy, and the data suggests that it is of value to patients. The foundations for choosing a combination therapy were laid through preclinical work at the La Jolla Institute. “
Matthias von Herrath, MD, LJI professor
Type 1 diabetes is an autoimmune disease that occurs when the body’s T cells mistakenly target insulin-producing beta cells in the pancreas. When beta cells die, the body loses its ability to regulate glucose levels, which can eventually lead to severe organ damage and death.
One challenge in treating type 1 diabetes is that therapies that target “system-wide” T-cell responses also run the risk of impairing the immune system’s ability to fight real threats such as viruses and bacteria.
The von Herrath laboratory at LJI focuses on uncovering the molecular triggers of type 1 diabetes. Her work has shown ways to modulate parts of the immune system without suppressing the function of the entire immune system.
In 2012, the Herrath Laboratory published an immunity study showing the role of the interleukin (IL) -21 receptor in the uptake of harmful T cells by the pancreas. Follow-up studies showed that an anti-IL-21 antibody can disrupt this signal and possibly protect the pancreas from attack.
Since the anti-IL-21 antibody appears to only affect one group of T cells, von Herrath and his colleagues believed that the antibody could help treat type 1 diabetes without depressing the entire immune system.
In 2017, Novo Nordisk published a preclinical study in the Journal of Autoimmunity showing the effects of combination therapy consisting of an anti-IL-21 monoclonal antibody in combination with the FDA-approved type 2 diabetes drug liraglutide duration. Liraglutide has been shown to protect beta cell function. The study, which von Herrath co-authored, showed that this combination can reverse type 1 diabetes in a mouse model.
For the new study, von Herrath and his team tested the combination therapy in a randomized, placebo-controlled double-dummy-double-blind phase 2 study with parallel groups. Compared to the placebo group, patients who received the 54-week treatment had higher endogenous insulin secretion. No safety concerns were identified.
The researchers followed the study participants 26 weeks after the end of treatment and found that the effects subsided during that time. They also found no permanent adverse changes in the immune system. The researchers note that the combination therapy needs to be evaluated in a Phase 3 clinical trial for long-term safety and effectiveness.
In the future, von Herrath and his laboratory at LJI will concentrate on transferring their results on both type 1 diabetes and type 2 diabetes from the laboratory to the clinic.
The study, “Anti-Interleukin-21 Antibodies and Liraglutide in Preservation of β-Cell Function in Adults with Recent Type 1 Diabetes: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study” was fully funded by Novo Nordisk.
La Jolla Institute of Immunology
von Herrath, M. et al. (2021) Anti-interleukin-21 antibodies and liraglutide for the maintenance of β-cell function in adults with recent type 1 diabetes: a randomized, double-blind, placebo-controlled phase 2 study. The Lancet Diabetes and Endocrinology. doi.org/10.1016/S2213-8587(21)00019-X.