The EMDAC voted 10-7 to support the benefit-risks of teplizumab for delaying clinical type 1 diabetes.
5:30 PM Update: The EMDAC voted 10-7 to support the benefit-risks of teplizumab for delaying clinical type 1 diabetes.
After the vote, experts discussed their reasoning behind their individual vote.
The 10 experts in support of the vote noted that it was a major clinical need and beneficial to at-risk populations.
While 7 experts voted against teplizumab, they noted the significant result of the study, but had uncertainties about the target population, safety issues, and limited data set.
1:30 PM Update: The FDA presented their analyses during the meeting.
Lauren Wood Heickman, MD, a clinical reviewer at the FDA, gave an overview on the clinical development for teplizumab.
T1D was diagnosed by 2-hour plasma glucose ≥200 mg/dL on oral glucose testing or casual plasma glucose >200 mg/dL plus symptoms of diabetes (polyuria, polydipsia, weight loss).
The criteria had to be confirmed on 2 occasions at least 1 day apart. The presence of unequivocal hyperglycemia with acute metabolic decompensation was also considered diagnostic of T1D.
Wood Heickman noted that younger age at islet autoantibody development was associated with a higher risk of progression to T1D.
“Younger age at the time of antibody development is associated with a high risk of progression type 1 diabetes,” Wood Heickman said. “However, it is not clear if age impacts the risk of progression to type 1 diabetes once metabolic disturbance is present.”
Yu Wang, PhD, Statistical Reviewer, FDA presented the statistical assessment of teplizumab efficacy in the TN-10.
Wang also highlighted the differences among the 5 studies in a meta-analysis, with the results in a change in baseline in C-peptide area.
Data from oral glucose tolerance test (OGTT) was collected at 3 months, 6 months, and every 6 months after until T1D onset or end of study.
“The ratio for each level was estimated to illustrate the treatment effect and the study of TN-10 from baseline in the peptide AUC in the 2-hour glucose test,” Wang said.
Wang noted the treatment effect was statistically significant, and treatment was robust to sensitivity analysis.
However, Wang also noted the TN-10 had a small sample size as well as study design issues in evaluating the treatment effect of teplizumab on C-peptide AUC change from baseline.
11:00 Am Update: Today, the US Food and Drug Administration (FDA) are set to review the Biologics License Application (BLA) for teplizumab, an investigational candidate for the delay of type 1 diabetes (T1D) in at-risk individuals.
The Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) will review safety and efficacy of the BLA for teplizumab intravenous infusion, submitted by Provention Bio, Inc.
The BLA was based on TN-10 study data that found a single 14-day course of teplizumab delayed clinical disease and insulin-dependence by at least 2 years in pre-symptomatic patients with Stage 2 T1D, compared to placebo.
According to analysis, more than 800 patients receiving teplizumab in clinical studies and the treatment demonstrated the ability to preserve beta-cell function as shown by C-peptide.
The treatment was generally well-tolerated and safety data was consistent with previous analyses.
Main risks for the treatment included lymphopenia, transaminase elevations, rash, and cytokine release events, but investigators believe these events are manageable because teplizumab is given as a one-course regimen.
The treatment was granted Breakthrough Therapy Designation and given a Prescription Drug User Fee Act (PDUFA) action data of July 2.
This article will be updated during panel discussion, data review, and committee vote on Thursday afternoon.