The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Provention Bio regarding the Biologics License Application (BLA) for teplizumab for the delay of clinical type 1 diabetes (T1D) in at-risk individuals.
Teplizumab is an investigational anti-CD3 monoclonal antibody that has been shown to preserve beta cell function, reducing the need for exogenous insulin. In June 2021, the 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).
The BLA was supported by data from the phase 2 TN-10 study (ClinicalTrials.gov Identifier: NCT01030861), which 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. Follow-up data demonstrated a delay in onset of approximately 3 years (median of 32.5 months). Treatment with teplizumab was also reported to reverse the decline in C-peptide levels.
In the CRL, the FDA noted that the BLA could not be approved because “a single, low-dose pharmacokinetic/pharmacodynamic (PK/PD) bridging study in healthy volunteers to compare planned commercial product with drug product originating from a drug substance manufactured for historic clinical trials had failed to show PK comparability.” Product quality issues and manufacturing deficiencies were also included in the response letter; however, the Agency did not cite any clinical concerns. As part of the BLA resubmission, the FDA did request updated safety data.
“We will continue to work collaboratively with the FDA to hopefully secure approval of teplizumab and bring the first disease-modifying therapy for T1D to at-risk patients as soon as possible,” said Ashleigh Palmer, co-founder and CEO of Provention Bio. The Company is expected to have additional PK/PD data available from its ongoing phase 3 PROTECT trial (ClinicalTrials.gov Identifier: NCT03875729) later this quarter.
Provention Bio receives Complete Response Letter (CRL) to Biologics License Application (BLA) for teplizumab for the delay of clinical type 1 diabetes (T1D) in at-risk Individuals. [press release]. Red Bank, NJ: Provention Bio, Inc.; July 6, 2021.