The teplizumab antibody stops the destruction of pancreatic cells that produce insulin in children and adolescents who begin to have symptoms of type 1 diabetes, the most serious form of the disease. But its effectiveness in controlling blood sugar levels and reducing the need for insulin injections is modest, so the eventual usefulness of teplizumab in the treatment of diabetes is still uncertain.
These are the main conclusions of the Protect clinical trial, in which 328 patients from Europe and North America participated, which were presented today in The New England Journal of Medicine and at the congress of the International Society of Pediatric and Adolescent Diabetes that took place. celebrated in Rotterdam (Netherlands).
“It is an advance that indicates that we are going in the right direction to improve the treatment of diabetes by acting on the immune system,” says Jesús Blanco, specialist in endocrinology and nutrition at the Hospital Clínic in Barcelona. But “improvement may not be enough to change clinical practice.”
There were high expectations for teplizumab, an immunosuppressive drug that reduces the immune system’s attack on the beta cells of the pancreas. The destruction of these cells that produce insulin is what prevents people with type 1 diabetes from being able to control their blood sugar level on their own, so they need to inject themselves with the hormone.
There are around 50,000 people with type 1 diabetes in Spain, most of them diagnosed in childhood or adolescence. It is a chronic disease that can evolve into cardiovascular, kidney, peripheral nervous system and retinal diseases. It is different from the much more common type 2 diabetes, which is usually diagnosed in adults.
In a previous clinical trial, teplizumab had slowed the progression of type 1 diabetes in minors diagnosed when the destruction of pancreatic beta cells had already begun but before the appearance of symptoms of the disease. The results of that study led to the drug being approved last November in the US for this type of patient. It is expected that it will also be approved in Europe in the coming months.
But it remained to be clarified whether teplizumab can stop the progression of diabetes when the first symptoms have already appeared and there are fewer beta cells left to save in the pancreas. This is the mystery that the Protect study had to clear up, in which the efficacy and side effects of teplizumab were compared with a placebo in children between 8 and 17 years old recently diagnosed with type 1 diabetes.
Participants received two cycles of treatment, one six months after the other. Each cycle consisted of a daily dose administered by intravenous injection for twelve days.
A year and a half after the start of treatment, 95% of patients treated with teplizumab maintain an adequate level of C-peptide, which indicates adequate production of insulin in the pancreas. Among patients who received placebo, the percentage drops to 79%, reflecting a more rapid degradation of insulin-producing cells.
Demonstrating a significant reduction in C-peptide levels was the main objective of the study, which has been met, paving the way for teplizumab to be approved to treat minors after the onset of symptoms.
However, the improvements observed in the secondary objectives of the study have not been found to be statistically significant. A year and a half after the start of treatment, the percentage of time that an adequate blood glucose level is maintained is 68.6% in patients treated with teplizumab and 64.6% among those who received placebo.
The number of major episodes of hypoglycemia – an excessive reduction in glucose level – is 4.66 per year if you have received teplizumab and 4.24 if you have received placebo.
The data indicate that the outcome of patients treated with teplizumab is slightly better, but the improvement is too small to reach the levels of statistical significance predefined in the study.
Side effects, which included headache, gastrointestinal symptoms, and skin rashes, were mostly mild, transient, and resolved spontaneously.
“The treatment of type 1 diabetes is evolving towards therapies that modulate the immune system’s response against pancreatic cells and that can stop the progression of the disease. The results of the Protect study are progress in this direction,” says Jesús Blanco, from the Clínic hospital.
Looking ahead to the coming years, more precise immune therapies have begun to be developed to protect the pancreas more effectively and with fewer adverse effects. In the future, Blanco anticipates, immune therapies will be combined with regenerative medicine to restore the beta cells of the pancreas. With this combination of therapies, it is not only expected to slow the progression of diabetes, but even cure it.
