Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association (ADA) 80th Scientific Sessions in June. They were published online November 18 The England Journal of Medicine.
In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.
Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
An Intermediate Step Toward a Cure…
Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, told Medscape Medical News.
“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure…. There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Quattrin, of the Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York.
But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.
He said of golimumab, “the effect is actually very small…. There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game-changers.”
If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York City.
With Golimumab, Higher C-Peptide, Lower Insulin Requirement
Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.
The drug resulted in lower insulin use (0.51U/Kg/d vs 0.69 U/kg/d), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs 0.24 U/kg/d; P=.001).
The mean percent decrease of C-peptide production from baseline was 12% with golimumab, vs 56% with placebo.
Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (
No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab, vs 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs 19%).
Immunotherapy: Which One, and When Should It Start?
These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.
However, Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.
Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.
Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.
A Janssen spokesperson told Medscape Medical News that the company isn’t planning to further develop golimumab for use in type 1 diabetes.
“Our focus is to apply insights from the phase 2…proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.
To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.
Quattrin said, “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”
Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial, “We should also be mindful that this treatment debate is first-world centric.
“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he writes.
Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Accili is founder and director of Forkhead Therapeutics Corp.
N Engl J Med. Published online November 18, 2020.
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