FDA Expands Approval of Drug to Stave Off Type 1 Diabetes

The FDA expanded the approval for teplizumab (Tzield), a biologic that delays the progression of preclinical type 1 diabetes to the symptomatic form, to include treatment in kids as young as 1 year, Sanofi announced on Wednesday.

The first and most common peak for type 1 diabetes diagnosis in kids occurs between the ages of 4 and 7; the second peak occurs at ages 10 to 14. Teplizumab was previously approved for children ages 8 years and older.

“This approval opens an important new chapter in diabetes care for young children with stage 2 type 1 diabetes and their families,” said Kimber Simmons, MD, MS, of the Barbara Davis Center in Aurora, Colorado, in a statement. “This is especially important because these children are often at the highest risk of progressing quickly and without warning.”

“Delaying the onset of stage 3 type 1 diabetes during the years when management is often most difficult because of a child’s small size and dependence on caregivers could have a truly meaningful impact for families,” she added.

Type 1 diabetes progresses through four stages. At stage 2, patients are still presymptomatic but have dysglycemia and at least two related autoantibodies. Stage 3 is the clinical stage, in which a significant portion of beta cells are destroyed and patients typically require insulin to manage hyperglycemia.

Teplizumab is a CD3-directed monoclonal antibody believed to work by deactivating the immune cells that attack insulin-producing cells, while increasing the proportion of cells that help moderate the immune response.

The PETITE-T1D study lent support for the approval. The open-label trial administered a once-daily intravenous infusion for 14 consecutive days to 23 patients with stage 2 type 1 diabetes. The average participant age was 4.8.

In an interim analysis, the estimated probability of lack of progression to stage 3 at 89.6% at 1-year follow-up. Two participants progressed to stage 3. Serum teplizumab concentrations peaked at day 14.

No new safety risks were identified, and most adverse events were mild to moderate. Three participants discontinued treatment due to anemia, elevated liver enzymes, and maculo-papular rash.

Most participants experienced gastrointestinal disorders (78.3%), infections (78.3%), and skin/subcutaneous tissue disorders (73.9%). The most frequently reported treatment-emergent adverse events during the dosing period and up to 28 days after the last dose were vomiting (52.2%), rash (43.5%), diarrhea (30.4%), decreased lymphocyte count (30.4%), decreased white blood cell count (26.1%), and maculo-papular rash (26.1%).

The drug has no contraindications, but the label warns of cytokine release syndrome, serious infections, lymphopenia, hypersensitivity reactions, and timing of vaccinations. A boxed warning also emphasizes the risk for viral reactivation.

Sanofi noted that the drug is also under FDA review to delay the further progression of type 1 diabetes in patients 8 years and older who are already in stage 3.