The FDA issued a Complete Response Letter, halting Provention Bio's type 1 diabetes prevention drug.
Provention Bio has received a Complete Response Letter (CRL) from the FDA in response to its Biologics License Application (BLA) for the company’s drug teplizumab, which aims to delay type 1 diabetes (T1D) among at-risk individuals, effectively delaying approval of the first potential disease-modifying treatment for these patients.
According to the company, the FDA said that the single, low-dose pharmacokinetic/ pharmacodynamic (PK/PD) bridging study of teplizumab in healthy volunteers—which compared the planned commercial product with the product originating from the drug substance used in clinical trials—failed to show PK compatibility.
“As PK remains the primary endpoint for demonstration of comparability between the 2 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 told Provention Bio. The letter was not released, but the company quoted from the letter in its statement.
The CRL also added deficiencies at a fill/finish manufacturing facility used by Provention Bio need to be resolved prior to approval, although these concerns were not specific to teplizumab.
The announcement comes after an FDA panel voted 10-7 to support approval of the drug in late May, and the American Diabetes Association (ADA) subsequently included teplizumab in its updated Living Standards of Care.
The Endocrinologic and Metabolic Drugs Advisory Committee based its recommendation on safety and efficacy data from the TN-10 Study, which found that a 14-day treatment course of teplizumab delayed on the onset of insulin-dependent, clinical-stage disease by an average of at least 2 years in patients with presymptomatic stage 2 T1D, compared with placebo.
Some panel members had concerns with the small size of the study and the higher rate of serious side effects in patients who received the therapy.
Provention Bio plans to collect additional data later this quarter from a sub-study in patients receiving 12 days of therapy in the ongoing phase 3 PROTECT trial; the company said after review, it will decide "whether to submit these data to the FDA for its review, along with any other relevant data and analyses based on our ongoing discussions with FDA, to support PK comparability or otherwise justify why PK comparability is not necessary."
No clinical deficiencies related to teplizumab’s efficacy and safety data packages submitted to the BLA were included in the CRL, but the administration requested a safety update be included in the company’s resubmission.
“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.