FDA Issues Complete Response Letter for Type 1 Diabetes Antibody

Provention Bio recently announced that it received a complete response letter (CRL) from FDA in response to its biologics license application for its antibody, teplizumab, which aims to delay clinical type 1 diabetes.

In the letter, FDA stated that a single, low-dose pharmacokinetic/ pharmacodynamic bridging study in health volunteers failed to show pharmacokinetic comparability.

But FDA did not cite any specific deficiencies related to the efficacy and safety data packages submitted. And the agency confirmed the acceptability of the proposed proprietary name for teplizumab.

"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,” a Provention Bio spokesperson said in the announcement. 

Provention Bio asserts that any roadblocks have been addressed in amendments already submitted to the biologics license application or can be addressed in the short term. 

But FDA cited various considerations regarding product quality and stated that it has not reviewed several amendments already submitted by Provention Bio in response to certain chemistry, manufacturing, and controls information requests. 

FDA requested that Provention Bio provide a safety update as part of its biologics license application resubmission. 

The letter also contained other comments and recommendations that do not impact approvability and general guidance regarding the resubmission process, the spokesperson added.

"We know the T1D community is urgently awaiting therapeutic advancements to address their medical needs and believe our collective passion and commitment will continue to drive us forward to meet this goal,” said Ashleigh Palmer, co-founder and CEO of Provention Bio. 

“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,” Palmer continued. 

More than 1.6 billion Americans have type 1 diabetes, a condition that is generally diagnosed in children and young adults. Typically, this disease takes over a decade off a person's life and life expectancy is reduced by 16 years on average for individuals diagnosed before the age of 10.

Teplizumab is an anti-CD3 monoclonal antibody being developed for the delay of clinical type 1 diabetes.

In a previous study, a single 14-day course of teplizumab delayed insulin-dependent, clinical-stage disease by at least two years in pre-symptomatic patients with stage 2 type 1 diabetes, compared to placebo. 

And in studies of newly diagnosed patients, teplizumab demonstrated the ability to preserve beta-cell function as shown by C-peptide, a measure of endogenous insulin production.