Provention Bio Inc. (PRVB) Provides Additional Regulatory Update on Biologics License Application for Teplizumab for the Delay or Prevention of Clinical Type 1 Diabetes in At-Risk Individuals

Provention Bio, Inc., (Nasdaq: PRVB), a biopharmaceutical company dedicated to intercepting and preventing immune-mediated disease, today announced the Company took part in an informal meeting with the U.S. Food and Drug Administration (FDA) on April 23, 2021, in connection with the FDA's ongoing review of the teplizumab Biologic License Application (BLA) for the delay or prevention of clinical type 1 diabetes (T1D). The purpose of this meeting was to discuss the FDA's considerations, thus far, regarding comparability between the Company's proposed commercial product and drug product used historically in clinical trials originating from drug substance manufactured by Eli Lilly over a decade ago.

The FDA reported at the meeting that it had concluded that the pharmacokinetic (PK) profiles of the two drug products evaluated in the Company's single, low-dose pharmacokinetic/pharmacodynamic (PK/PD) bridging study conducted in healthy volunteers are not comparable, since the intended commercial product did not meet the pre-specified 80-125% PK area under the curve (AUC) comparability target range. The FDA also stated that it cannot be certain if this observation is not clinically relevant, given that the relationship between transient lymphocyte reduction, a PD marker, which was comparable in the PK/PD bridging study, and clinical efficacy, has yet to be fully validated.

The FDA emphasized its understanding of the high unmet need associated with delaying the onset of clinical-stage T1D and reiterated their willingness to work with the Company to find a solution and path forward for the comparability issue. Nevertheless, the Company is reiterating previous guidance that the FDA's PK comparability considerations are likely to result in a delay in potential BLA approval timelines and that the specifics of such delay will depend upon the outcome of ongoing discussions with the FDA to find a solution, including potentially providing FDA reviewers with PK/PD data from the Company's on-going Phase 3 PROTECT study in newly diagnosed patients.

The FDA also informed the Company that it plans to mention its PK comparability review in the clinical pharmacology summary of its briefing materials for the Advisory Committee meeting on May 27th, along with a statement that the FDA is actively working with the Company to resolve the issue and that the focus of the Advisory Committee meeting is efficacy and safety of teplizumab. It is the Company's understanding that since the FDA's PK comparability considerations do not bear on the benefit-risk assessment of the TN-10 study clinical data package, no comparability related questions or discussion topics are planned for the meeting. The FDA also recommended that both the FDA and the Company update their Advisory Committee briefing materials to reflect the removal of the term "prevention" from the previously proposed indication, as the remaining term "delay" more accurately reflects the results of the TN-10 trial.

"We would like to thank the FDA for meeting with us to explain its PK comparability considerations, thus far, and especially for its willingness to work with us to find a path forward," stated Ashleigh Palmer, CEO and Co-Founder, Provention Bio. "We are also fully aligned with the FDA's recommendation to remove the term 'prevention' from the wording of teplizumab's initial indication and instead focus exclusively on delaying the progression of disease. We believe this will help to reinforce the fact that, while pre-symptomatic, T1D patients with two autoantibodies and dysglycemia already have the disease and may benefit from therapeutic options targeting the preservation of functional beta cell mass. We remain enthusiastic about the clinical efficacy and safety data submitted in connection with the BLA in support of teplizumab's potential to address the high unmet needs of pre-symptomatic T1D patients. Finally, we are looking forward to participating alongside the patient community, treating physicians, and additional members of the T1D community in the upcoming FDA Advisory Committee Meeting, the importance of which could not be more clear at this juncture."

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