Phase 2 Trial of Combination Therapy for Type 1 Diabetes Shows Promise

Compared to the placebo group, patients with diabetes who received a 54-week course of treatment had higher levels of endogenous insulin secretion with no identified safety concerns.

A recent trial investigating a combination therapeutic candidate for adults with recent-onset type 1 diabetes (T1D) has shown promising results, offering a potential way to treat the autoimmune disease without leaving the body vulnerable to infectious disease.

The randomized, double-blind, placebo-controlled trial was funded by Novo Nordisk, with results published in The Lancet Diabetes and Endocrinology. The therapeutic candidate combined anti-interleukin (IL)-21 antibody with liraglutide, which is a commonly prescribed drug for diabetes. This approach is based on research from the lab of Matthias von Herrath, MD, a professor at the La Jolla Institute for Immunology.

“This is the first large trial for a combination therapy, and the data suggest it has value for patients,” von Herrath said in the press release.

T1D occurs when the body’s own T cells mistakenly target insulin-producing beta cells in the pancreas. When these beta cells die, the body loses its ability to regulate glucose levels, which can eventually lead to severe organ damage and death. This presents a challenge in treating type 1 diabetes, because therapies targeting system-wide T cell responses also risk hindering the immune system’s ability to fight real threats, such as viruses and bacteria, according to the study.

Researchers, therefore, focused on uncovering the molecular triggers of T1D. Their work has pointed to some ways to modulate parts of the immune system without suppressing overall immune system function. In 2012, the investigators published a study showing the importance of the IL-21 receptor in allowing harmful T cells into the pancreas. Follow-up studies showed that an anti-IL-21 antibody could interrupt that signal and potentially shield the pancreas from attack.

Notably, because the anti-IL-21 antibody appears to only affect a group of T cells, von Herrath and his colleagues believed the antibody might help treat T1D without dampening the overall immune system. A pre-clinical study published in 2017 showed the effects of a combination therapy that consisted of anti-IL-21 monoclonal antibody combined with liraglutide, which has been shown to protect beta cell function. The study showed that this combination could reverse T1D in a mouse model, according to the researchers.

For the new study, von Herrath and his colleagues tested the combination therapy in a randomized, parallel-group, placebo-controlled, double-dummy, double-blind, phase 2 trial. Compared to the placebo group, patients who received the 54-week course of treatment had higher levels of endogenous insulin secretion. No safety concerns were identified.

The investigators followed up with study participants for 26 weeks after the treatment ended and found that the effects diminished during that time. They also found no lasting adverse changes to the immune system, although they noted that the combination therapy will need to be assessed for long-term safety and efficacy in a phase 3 clinical trial.

REFERENCE

LJI research leads to promising combination therapy for type 1 diabetes [news release]. La Jolly Institute for Immunology; March 9, 2021. https://www.lji.org/news-events/news/post/lji-research-leads-to-promising-combination-therapy-for-type-1-diabetes/. Accessed March 11, 2021.