UCSF, renowned for its extensive experience in conducting clinical trials for type 1 diabetes, persists in its commitment to advancing medical research by harnessing the power of immunotherapy.
According to a recent study, the use of the immunotherapy drug teplizumab can reduce the amount of supplemental insulin needed by children who have been diagnosed with type 1 diabetes, in order to maintain healthy blood sugar levels.
Type 1 diabetes affects approximately 8.4 million individuals globally. This autoimmune condition causes the immune system to attack and damage the insulin-producing pancreatic beta cells, which are responsible for regulating blood sugar levels. Teplizumab is a medication that can reduce the destruction of beta cells, thereby preserving the 10-40% that remain at the time of diagnosis. This preservation can make it simpler to manage type 1 diabetes by maintaining these vital beta cells.
Stephen Gitelman, MD, Mary B. Olney, MD/KAK Distinguished Professor in Pediatric Diabetes and Clinical Research at the UCSF Diabetes Center, emphasized the arduous nature of effectively managing type 1 diabetes, despite the availability of advanced tools like newer insulin analogues, insulin pumps, and continuous glucose sensors. He particularly highlighted the heightened difficulties faced by children and adolescents grappling with this condition.
Dr. Gitleman, a prominent researcher at UC San Francisco, spearheads the extensive PROTECT study on teplizumab across 61 sites in the United States, Europe, and Canada. The study’s outcomes, which were published on October 18, 2023, in the esteemed New England Journal of Medicine, provide compelling evidence to advocate for the broadening of teplizumab treatment. This expansion would extend beyond its current approval for individuals who are at risk of developing type 1 diabetes but have not yet received a diagnosis.
Gitelman stated that this trial marks the initial phase 3 study of immunotherapy following the diagnosis of type 1 diabetes, which achieved its primary objective and demonstrated a prolonged advantage for a duration of 18 months.
Phase 3 trials serve the purpose of validating the results obtained from earlier, more limited trials, ensuring the safety and efficacy of a drug for its intended purpose. Immunotherapy endeavors to alter an individual’s immune response, either to reinstate a state of equilibrium or to sustain overall well-being.
Gitelman emphasized that the study was conducted amidst the COVID-19 pandemic and revealed that patients did not exhibit increased vulnerability to the virus, nor did they encounter any difficulties in fighting off other infections.
Symptoms of type 1 diabetes
In the PROTECT trial, children between the ages of 8 and 17 who were diagnosed with type 1 diabetes were randomly assigned to receive either teplizumab or a placebo within six weeks of their diagnosis. The treatment, which involved intravenous administration of teplizumab, was given for a period of 12 days at the beginning of the study, followed by another round of treatment six months later.
The allocation of participants was done randomly, with a ratio of 2:1, to receive either teplizumab or a placebo that matched it. Among the 217 patients in the teplizumab group, a greater number of their insulin-producing beta cells were preserved, and they also showed a tendency to require lower doses of supplemental insulin in order to maintain their glucose levels within a near-normal range. In contrast, the 111 children who received the placebo did not exhibit the same level of preservation of beta cells or reduction in supplemental insulin dosage.
According to Gitelman, a greater number of patients who received teplizumab achieved a “clinical remission” compared to those who received the placebo. This remission allowed them to maintain tight control over their blood sugar levels with less supplemental insulin. However, it should be noted that a complete remission would entail not requiring insulin at all.
Similar to a powerful strike against the body’s immunity
The PROTECT study, which is currently underway, is the result of years of research aimed at finding ways to preserve pancreatic beta cells in individuals who have recently been diagnosed with type 1 diabetes.
Investigators previously conducted studies using broad, generalized immunosuppression in an attempt to protect the beta cells. Although these studies were successful, they were akin to using a sledgehammer on the immune system and could not be pursued further due to safety concerns associated with long-term immunosuppression. Subsequently, more targeted drugs were discovered, but they failed to progress beyond phase 2 trials. However, this phase 3 trial represents the first successful use of immune-modulation in preserving beta cells.
Gitelman is already contemplating future actions. His team is persistently monitoring the PROTECT patients to determine the duration of the current therapy’s effects. Additionally, they are exploring the possibility of administering additional teplizumab infusions to these patients or future ones at a later stage. Furthermore, they are evaluating the potential of combining the medication with other drugs that operate through complementary mechanisms to enhance its effectiveness.
Gitelman expressed his excitement and celebration regarding the current situation. However, he emphasized that this is just the beginning and they are already strategizing on how to further develop these findings and achieve more substantial outcomes.