FDA Expands Approval of Teplizumab for Children With Type 1 Diabetes

The U.S. FDA has expanded the approval of teplizumab (Tzield) to include children aged 8 years and older who have been recently diagnosed with stage 3 type 1 diabetes, the stage at which symptoms of high blood sugar appear and insulin therapy becomes necessary. This expanded indication aims to help preserve remaining insulin-producing beta cells and potentially slow disease progression in newly diagnosed pediatric patients.

Condition

Type 1 diabetes (T1D) develops in stages, which are determined by two things: the presence of certain proteins in the blood called autoantibodies and blood sugar levels.

Autoantibodies are proteins the immune system makes that mistakenly attack the body's own cells. In T1D, these autoantibodies target the cells in the pancreas that produce insulin. The key autoantibodies associated with T1D include insulin autoantibody, glutamic acid decarboxylase autoantibody, IA-2 autoantibody, and zinc transporter 8 autoantibody.

The three stages of T1D are defined as follows:

• Stage 1 is when an individual has two or more of these autoantibodies in their blood, but their blood sugar levels are still normal. At this stage, there are no symptoms, but the immune system has already begun attacking insulin-producing cells.

• Stage 2 occurs when an individual still has these autoantibodies, but their blood sugar levels have become abnormal. This is typically detected through a blood sugar test, such as an oral glucose tolerance test or a hemoglobin A1c test. There are still no obvious symptoms at this stage.

• Stage 3 is when an individual begins experiencing symptoms caused by high blood sugar, such as frequent urination, excessive thirst, and fatigue. At this point, the patient requires insulin therapy to manage their blood sugar levels.

Data Supporting Tzield

A large clinical trial called the PROTECT Study looked at whether teplizumab could slow down the loss of the body's own insulin production in children and teenagers recently diagnosed with Stage 3 T1D. The study was a randomized, double-blind, placebo-controlled trial. This means patients were randomly assigned to receive either teplizumab or a placebo (an inactive treatment), and neither the patients nor the research team knew which treatment each patient was receiving. Patients received their assigned treatment once daily through an IV for 12 days, followed by another 12-day course of treatment (drug or placebo) six months later.

The study included 328 patients between the ages of 8 and 17 who had been diagnosed with Stage 3 T1D within the past six weeks. All patients in the study still had some insulin-producing cells (called beta cells) that were working at the time they enrolled.

The study measured how well the beta cells were still working at 78 weeks (about 18 months) by testing levels of a protein called C-peptide in the blood. C-peptide is a reliable indicator of how much insulin the body is still producing on its own. At 78 weeks, patients who received teplizumab showed a significantly smaller decline in beta cell function compared to patients who received the placebo. This means teplizumab helped slow down the loss of the body's own insulin production.

Safety Information

Tzield has a boxed warning, the most prominent safety warning that is required on a prescription drug label. Serious life-threatening cases of viral reactivation, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation, have been reported with Tzield. Patients who are immunocompromised are at increased risk. Most serious cases occurred in patients who continued Tzield treatment despite persistent, severe lymphopenia (a reduction in lymphocytes, a subset of white blood cells). Prior to beginning treatment, patients should be tested for active EBV and CMV infection.

Other known side effects of Tzield are cytokine release syndrome, which typically occurs within the first five days of Tzield, with symptoms of fever, feeling tired (fatigue), muscle and joint pain, nausea with or without vomiting, and increased liver enzymes in the blood. Severe allergic reactions have occurred in patients using Tzield. The most common side effects of Tzield are vomiting, rash, increased liver transaminase (a blood test that detects liver stress or damage) and headache. In addition, Tzield is associated with a reduction in white blood cells (leukopenia), including a reduction in different types of white blood cells (lymphopenia and neutropenia) that can increase the risk for certain infections.

Tzield was approved under accelerated approval for this indication. Approval was granted to Sanofi.