The Food and Drug Administration (FDA)’s Endocrinologic and Metabolic Drugs Advisory Committee voted 10 yes and 7 no on whether the benefits of teplizumab outweigh the risks in support of approval to delay clinical type 1 diabetes (T1D).
Teplizumab, an anti-CD3 monoclonal antibody, has been shown to preserve beta-cell function, reducing the need for exogenous insulin. The recommendation was based on data from the phase 2 TN-10 Study (ClinicalTrials.gov Identifier: NCT01030861). Relatives (aged 8 years and older) of individuals with T1D were randomly assigned to receive intravenous infusions of either teplizumab (n=44) or placebo (n=32) for 14 consecutive days; oral glucose tolerance tests were used to assess progression to clinical T1D every 6 months.
Results showed that a single 14-day infusion course of teplizumab delayed the onset of clinical disease and insulin dependence in at-risk (stage 2) T1D patients by at least 2 years compared with placebo. Recent follow-up data demonstrated a delay in onset of approximately 3 years (median of 32.5 months). Additionally, teplizumab treatment was reported to significantly reverse the decline in C-peptide levels.
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval. The panel did note the relatively small number of patients exposed to teplizumab in the TN-10 study, as well the potential for adverse events such as cytokine release syndrome, transient lymphopenia, hepatic enzyme and bilirubin elevations, immunosuppression, infection, and a possible risk of future malignancy.
A Prescription Drug User Fee Act (PDUFA) action date of July 2, 2021 has been set for the application.
- FDA advisory committee votes in favor of the benefits of teplizumab outweighing the risks in support of approval to delay clinical type 1 diabetes (T1D). [press release]. Red Bank, NJ: Provention Bio, Inc; May 27, 2021.
- FDA Briefing Document Endocrinologic and Metabolic Drugs Advisory Committee Meeting: Teplizumab. Accessed June 1, 2021. https://www.fda.gov/media/149388/download.