Provention Bio says the US FDA’s Chemistry, Manufacturing and Controls (CMC) concerns relating to its type 1 diabetes candidate teplizumab are addressable in the short-term.
Provention Bio has hit a snag in its Biologics License Application (BLA) for teplizumab (PRV-031), its investigational anti-CD3 monoclonal antibody (mAb) being developed for the delay of clinical type 1 diabetes.
On July 2, the firm received a Complete Response Letter (CRL) from the US Food and Drug Administration (FDA) citing concerns relating to pharmacokinetic/pharmacodynamic (PK/PD) data and product quality.
For the former, the FDA said: “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 company is confident additional PK/PD data can be collected and submitted to the FDA, if necessary.
For the latter, a spokesperson from the company told BioProcess Insider: “The FDA cited several additional considerations to product quality. We have not publicly listed out the considerations, however did note that many of these had already been addressed in amendments we had submitted to the FDA, which the FDA noted they had not reviewed in time for the CRL action.
“We’ve assessed the few new considerations and our CMC team has deemed them to be addressable in the short-term.”
The FDA also highlighted deficiencies conveyed during a recent general inspection at a fill/finish manufacturing facility used by the Provention, though not specific to teplizumab, and said these will need to be resolved before a potential approval.
“We don’t view these observations having an effect on our ability to manufacture the drug,” we were told. “These are observations which mostly have already been addressed and the others are quickly addressable.”
The drug substance for teplizumab is made by CDMO partner AGC Biologics from its facility in Bothell, Washington, but the firm has not divulged where the drug product is produced.
Provention Bio’s share price dropped 30% following the CRL announcement.