ADC Reviews

FDA Delays Teplizumab License Application


RED BANK, N.J., June 30, 2022 /PRNewswire/ -- Provention Bio, Inc. (Nasdaq: PRVB) (the "Company"), a biopharmaceutical company dedicated to intercepting and preventing immune-mediated diseases, today announced that the U.S. Food and Drug Administration (FDA) has extended its review period by three months for the Biologics License Application (BLA) for teplizumab. The extended User Fee Goal date is November 17, 2022. The Company was also informed that if no major deficiencies are identified during the review period, the FDA plans to communicate proposed labeling and, if necessary, any post-marketing requirement or commitment requests by October 17, 2022.

Provention Bio

Recently, Provention announced that the US FDA has extended the Biologics License Application (BLA) of the company’s anti-CD3 monoclonal antibody teplizumab to delay type 1 diabetes (T1D) in high-risk individuals by 3 months, with a new PDUFA date of November 17, 2022. day. The FDA said the additional information Provention submitted earlier this month was a significant amendment to the BLA (biologics license application) and required additional time for review.

Provention was also told that if no significant deficiencies are identified during the review period, the FDA plans to communicate by October 17, 2022 about the proposed indication and any postmarketing or commitment requirements, if necessary.

Teplizumab is a monoclonal antibody that targets the CD3 antigen on the surface of T cells. It mainly binds to CD3 on the surface of effector T cells and inhibits its attack on islet β-cells, thereby reducing the damage to islet β-cells. The Fc region of teplizumab was designed into an Fc receptor non-binding (FNB) structure through amino acid modifications, thereby reducing its binding to complement and Fc receptors and reducing the associated toxicity.

Teplizumab’s road to market can be described as twists and turns. On July 6 last year, the FDA refused to approve teplizumab. The reason is that in a single-dose, low-dose pharmacokinetic/pharmacology (PK/PD) bridging study in healthy volunteers, the proposed product was compared with the product previously used in clinical trials and failed to show PK comparability.

Since PK remains the primary endpoint to demonstrate comparability of the two products, FDA requires the company to appropriately establish PK comparability between the proposed product and the clinical trial product, or provide other data sufficient to demonstrate that PK comparability is not necessary.

In January, Provention received FDA approval to resubmit the BLA application for teplizumab. Provention said at the time that the FDA’s concerns about comparability had been addressed, and the FDA accepted the application in March. Because Provention has previously been granted breakthrough therapy designation by the FDA, the approval time can be shortened to 6 months from the normal 10 months.