The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) denying approval for Provention Bio’s type 1 diabetes (T1D) prevention drug teplizumab.
In its CRL, the FDA said a study of healthy volunteers failed to demonstrate that the planned commercial product is comparable to its older version used in historic clinical trials.
‘As pharmacokinetics (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 justifies why PK comparability is not necessary,’ the FDA added.
Provention Bio is expecting relevant additional PK/pharmacodynamic (PD) data from an ongoing sub study in patients receiving 12 days of therapy in an ongoing phase 3 trial of newly diagnosed T1D patients later this quarter.
Depending on the results of this sub study, the company may then submit the data to the FDA for review, to support PK comparability or ‘otherwise justify why PK comparability is not necessary’.
The FDA also cited several additional concerns relating to product quality, although Provention Bio said that it believes these have either already been addressed in amendments to the biologics licence application (BLA) or can be addressed in the ‘short term’.
The company acknowledged that the FDA had not reviewed several amendments already submitted in response to certain chemistry, manufacturing and controls (CMC) information requests.
“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 chief executive officer 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,” she added.
Earlier this year, Provention Bio said that previously disclosed issues with the PK comparability for the drug – which were not discussed during a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee in May – were ‘likely’ to result in a delay to the potential BLA approval timelines.