FDA cites pharmacokinetic comparability considerations remained outstanding, while no clinical deficiencies on efficacy and safety were reported.
The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for a Biologics License Application for teplizumab in the delay of type 1 diabetes (T1D) in an at-risk population.
In the CRL, the FDA stated that Provention Bio failed to show pharmacokinetic (PK) comparability in the clinical trials.
The FDA cited a single, low-dose pharmacokinetic/pharmacodynamic (PK/PD) bridging study in healthy volunteers comparing planned commercial products originating from drug substances manufactured for historic clinical trials failed to show PK comparability.
“As PK remains the primary endpoint for demonstration of comparability between the two products, you will need to establish PK comparability appropriately between the intended commercial product and the clinical trial product or provide other data that adequately justify why PK comparability is not necessary,” the FDA wrote in a statement.
In the CRL, the FDA addressed additional considerations related to product quality, which the company has indicated has already been addressed.
Further, the FDA stated that deficiencies at a fill/finish manufacturing facility used by Provention Bio will need to be resolved, without specificity to teplizumab.
No clinical deficiencies in the efficacy and safety data submitted to BLA were cited by the FDA and the proposed proprietary name for teplizumab was accepted.
In addition, the FDA requested a safety update in the BLA resubmission.
Data on PK/PD is expected to be collected from a substudy in patients in the Phase 3 PROTECT trial, who are newly diagnosed T1D patients and currently undergoing 12-days of therapy.
“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 in a statement.
Teplizumab is an investigational anti-CD3 monoclonal antibody developed for the delay of clinical type 1 diabetes (T1D) in at-risk individuals.