Provention Bio slapped with FDA rejection for diabetes hopeful teplizumab

After scraping through a tough advisory committee in March, the FDA has returned a verdict for Provention Bio’s Type 1 diabetes medicine: It’s a no.

Specifically, the FDA has slapped a complete response letter on Provention for teplizumab, which was gunning for an approval to help delay clinical Type 1 diabetes in at-risk individuals.

In the trial that underpinned the drug’s application, Provention said teplizumab delayed the onset of Type 1 diabetes by a median of two years. That delay could help patients avoid diabetic ketoacidosis, a life-threatening complication of diabetes.

Back in March, FDA experts assessing the drug raised concerns about how small the study was—it didn’t meet its enrollment goal and wound up testing teplizumab in just 44 patients—and about the fact that the study did not follow patients after their diabetes diagnosis.

The company also submitted safety data from other trials of the drug in another indication, which the FDA reviewers noted were not a perfect comparison.

RELATED: Provention Bio brought back down to earth as FDA panel narrowly backs diabetes prevention drug

Now, the FDA is sharing its own concers, many of which were predicted. In a release from the biotech (the FDA doesn’t publicize complete response letters itself), the FDA stated 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,” the FDA said, as quoted by Provention.

The FDA is also asking for a “safety update” as part of its BLA resubmission, though Provention gave no specifics here.

The biotech said it expects “relevant additional” PK/PD data out from a PK/PD sub-study in patients receiving 12 days of therapy in the ongoing phase 3 Protect trial in newly diagnosed Type 1 diabetes patients “later this quarter.”

These data “will determine whether to submit these data to the FDA for its review,” Provention said, “to support PK comparability or otherwise justify why PK comparability is not necessary.”

And it doesn’t end there: There were also some manufacturing issues. The FDA uncovered “certain deficiencies” amid a recent general inspection at a fill/finish manufacturing facility, and, though not specific to teplizumab, this will need “to be resolved before approval.”

“The CRL contained other comments and recommendations that do not impact approvability, as well as general guidance regarding the resubmission process,” but again gave no details about these.

We do know that this will cause delay and likely more expense, and further knocks back the biotech, which had been flying high ahead of its advisory committee though was brought back to Earth by its squeezing past.

The company had been bullish that it could bypass some of these issues, but clearly, the FDA had other ideas.

“We want to recognize the patients, their families, study investigators, clinicians and T1D champions that have played such a crucial role in the development of teplizumab and thank our partners and our team of dedicated employees and consultants for their outstanding contributions,” said Ashleigh Palmer, co-founder and CEO of Provention Bio.

“We also want to acknowledge the efforts of Drs. Yanoff and Unger and the review team at the FDA, who have worked so closely and transparently with us throughout the priority review of our BLA for this Breakthrough Therapy drug.

“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. 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.”

The biotech shares were off 20% premarket on the news.