The FDA Issues Complete Response Letter for Teplizumab

Late on Friday, July 2, the FDA issued a Complete Response Letter regarding Provention Bio’s Biologics License Application for teplizumab for the delay of type 1 diabetes in at-risk people.

The agency indicated that a single, low-dose pharmacokinetic/pharmacodynamic (PK/PD) bridging study in healthy volunteers to compare planned commercial product with drug product originating from drug substance manufactured for historic clinical trials had 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,” FDA officials said, according to a press release issued by the company.

Provention Bio expects relevant additional PK/PD data being, or to be, collected from a PK/PD substudy in patients receiving 12-days of therapy in the ongoing phase 3 PROTECT trial in newly diagnosed T1D patients later this quarter. These data will be analyzed by independent, unblinded third-parties to maintain the integrity of this placebo-controlled trial.

In the CRL, the FDA cited several additional considerations related to product quality, which company officials believe have either been addressed in amendments already submitted to the BLA or can be addressed in the short-term.

“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,” Ashleigh Palmer, co-founder and CEO of Provention Bio said in a statement.

In late May, the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) of the FDA voted 10-7 in favor of approving the drug, noting that the benefits of teplizumab outweigh the risks in delaying treatment for T1D.

The EMDAC based its recommendation on safety and efficacy data from the pivotal TN-10 study in which a single 14-day course of teplizumab delayed insulin-dependent, clinical-stage disease by a median of at least 2 years in presymptomatic patients with Stage 2 T1D compared with placebo, executives from Provention Bio said in a press release.

Previously, analysts have said a therapy such teplizumab was needed because the number of diagnosed prevalent cases of type 1 diabetes (T1D) is expected to grow to 4.7 million cases by 2026 in eight major markets globally, according to GlobalData.

However, the uptake of teplizumab could be hampered by the fact that T1D screening is not clinical practice in the United States, GlobalData Pharma Analyst Samisha Khangaonkar said in statement.

“Key opinion leaders interviewed by GlobalData have stated that there is a considerably high unmet need for disease-modifying therapies and earlier diagnosis in T1D. Currently, patients with T1D are only diagnosed once symptoms of T1D occur. By that time, more than 80% to 90% of insulin-producing beta cells will have been destroyed, but evidence of beta cell autoimmunity through the presence of autoantibodies would have been present for many years prior.”