Provention warns FDA requests could delay diabetes approval

Provention Bio has warned the approval of teplizumab in Type 1 diabetes is likely to be delayed by a request for more information from the FDA. The advisory committee meeting is still scheduled to go ahead late next month, but the July 2 PDUFA date is now under threat.

One week ago, the FDA told Provention Bio it has identified deficiencies “that preclude discussion of labeling and post-marketing requirements/commitments.” The FDA said the notice does not reflect a final decision on the information. On the same day, the FDA used a meeting to discuss the advisory committee with Provention Bio to say its pharmacokinetic review indicates a need for more data.

Exactly what that means for Provention Bio’s application remains unclear. CEO Ashleigh Palmer set out what is known at this stage on a conference call with investors shortly after disclosing the FDA’s feedback. 

“These circumstances increase the likelihood that there will be a delay in the timelines within which teplizumab has the potential to be approved by the FDA. We certainly appreciate that this update creates a level of uncertainty around timeline. However, we also believe it would be a disservice to you as shareholders … for us to speculate at this point on either the steps required or any additional time it might take to obtain FDA approval,” Palmer said.

The uncertainty reflects the lack of information Provention Bio has currently. The FDA has said parts of the submission are deficient but is yet to provide full details of the problem or what it will take to resolve it. 

On its call with Provention Bio, the FDA said additional data will be needed on pharmacokinetics. The request stems from an analysis of a study that compared drug product based on materials from two sources, namely AGC Biologics, which Provention Bio plans to use for commercialization, and Eli Lilly, which provided drug substance for the TN-10 study featured in the submission for approval.

Provention Bio has previously discussed differences in the pharmacokinetic area under the curve of products based on the two sources of drug substance. Palmer called the difference an “anomaly,” but the FDA has concluded the two products are not comparable. It is currently unclear whether the FDA sees the difference as a manufacturing issue. 

More details will emerge after Provention Bio meets with the FDA. Against that backdrop, Provention Bio is continuing to prepare for an advisory committee meeting that is set to go ahead despite the issues raised by the FDA with aspects of the submission. 

“We see the adcomm proceeding as a very encouraging sign that the agency's continuing with its review,” Palmer said. “We do not anticipate at this point that the advisory committee is a venue where PK/PD and manufacturing comparability is going to be discussed or reviewed.”

Shares in Provention Bio fell 40% in after-hours trading.