Teplizumab can delay the onset of type 1 diabetes (T1D) for about two years in children and young adults at very high risk of developing the disease.

The phase 2 international clinical trial involving Australian researchers comprised 76 children and young adults with a family history of T1D, at least two diabetes-related autoantibodies and evidence of dysglycaemia.

Participants were randomised to either a 14-day course of IV teplizumab or placebo and followed for over three years.

Teplizumab is a Fc receptor-nonbinding antibody to CD3 that reduces the actions of CD8+ T lymphocytes on targets such as beta cells.

The study, published in the New England Journal of Medicine, found time to a diagnosis of diabetes was delayed in the treated group compared to the control group (48.4 v 24.4 months).

By the end of the trial, 43% of the treated group had developed diabetes compared to 72% of the controls.

The study found the largest effect of teplizumab was seen in the first year after treatment.

The annualised rates of diagnosis of type 1 diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group.

Adverse events included spontaneously resolving lymphopenia and rash.

“The delay of progression to diabetes is of clinical importance, particularly for children, in whom the diagnosis is associated with adverse outcomes, and given the challenges of daily management of the condition,” the study said.

“Our findings support the notion that type 1 diabetes is a chronic T-cell–mediated disease and suggest that immunomodulation before the development of clinical disease can be useful.”

Associate Professor John Wentworth, who led the Australian arm of the study, told the limbic the results were incredibly encouraging and a proof of principle demonstration.

However there was a long way to go including proving cost effectiveness and some innovation around delivery of the drug.

“Potentially it is a very promising drug. The IV regimen is not ultimately how it would be used; it would have to be simpler and more effective.”

He envisaged a short, sharp treatment – probably a subcutaneous injection or administration via the nasal mucosa – that likely had to be repeated on the basis of a disease marker yet to be determined.

“Probably the autoimmunity attack waxes and wanes and we probably need to hit it with this drug at the right moment when the autoimmune attack is highest.”

Associate Professor Wentworth, from the Royal Melbourne Hospital and the Walter & Eliza Hall Institute of Medical Research, said the benefits from delaying T1D should not be underestimated.

“I think you could also envisage that if you could get through the teenage years and have them starting insulin as an adult that would be incredibly helpful.”

He said trials were currently held back because of the struggle to identify at-risk children.

In the meantime, teplizumab was likely to come onto the market as a new onset therapy for children.

“Probably it’s going to be most effective as a prevention therapy rather than a therapy for newly diagnosed children but the company is trying to get it approved as a new onset therapy because that is really a much easier market.”

“It hasn’t been a knock-out success for new onset treatment but the feeling is that you will probably need to retreat people which they haven’t really been allowed to do in the initial studies.”

An accompanying editorial in the NEJM said the results of the trial were “striking” and provided strong evidence about the pathogenesis of beta-cell destruction and the potential to modify the course of T1D with biologic agents.

“The duration and frequency of treatments, the long-term side effects of those therapies, the identification of subgroups of persons who do not have a response to the treatment, and the clinical course of persons who initially do have a response still need to be determined.”

“Nevertheless, we can finally say, 40 years after Eisenbarth, that there has been substantial progress in modulating the early course of type 1 diabetes.”