Provention Bio Provides Regulatory Update for Teplizumab At-Risk Type 1 Diabetes Approval Pathway
Provention Bio, Inc. provided an update on its ongoing efforts to address U.S. Food and Drug Administration (FDA) considerations cited in the Complete Response Letter (CRL) issued to the Company by the FDA on July 2, 2021, pertaining to comparability between the Company's planned teplizumab commercial product and clinical drug product used in historical trials of teplizumab. On November 18, 2021, the Company had a Type A meeting with the FDA to discuss the population pharmacokinetic (popPK) model to be used for the purpose of planned commercial and clinical drug product comparison. In preliminary meeting comments, the FDA approved the Company proceeding to populate the popPK model with data collected from patients receiving therapeutic doses of teplizumab in a pharmacokinetic/pharmacodynamic (PK/PD) substudy of the ongoing PROTECT Phase 3 trial in newly diagnosed type 1 diabetes (T1D) patients (Commercial Product N~30 patients, Clinical Drug Product N~130 patients). The Company's preliminary analysis from the popPK model produced the following top-line results: Geometric mean of the ratio of commercial to clinical drug product [90% Confidence Interval (CI)] 83.2% AUC Infinity [CI: 76.9 – 89.9], 85.3% AUC Day 13 [CI: 78.0 – 93.3] and 86.5% CMAX [CI: 83.9 – 89.3]. These results are not final and are subject to ongoing review of both the data and the popPK model by the FDA and the Company. As anticipated, given teplizumab's target mediated mechanism of clearance, the difference in exposure (AUC Day 13 and 0-infinity) between commercial product and clinical drug product observed in a prior single, fractional low dose PK/PD study in healthy volunteers is greatly reduced when the products are administered and compared in accordance with the higher therapeutic dosing regimen used in T1D patients. Along with previously reported physicochemical and pharmacodynamic data, as well as the immunogenicity and safety profiles, it is the Company's current opinion that, collectively, these preliminary results support comparability of the commercial product and clinical drug product. The FDA, the ultimate decision maker on the matter, is conducting an independent review of the data and may have a different opinion. The Company looks forward to further discussing these results with the FDA to support the FDA's review. Additionally, at the Type A meeting held on November 18, 2021, the FDA expressed its concurrence with the Company proceeding to schedule a Type B, pre-Biologics License Application (BLA) re-submission meeting. Over 1.6 million Americans have T1D, an autoimmune disease caused by the destruction of beta cells. Diagnosis of T1D usually occurs in children and young adults, but it can happen at any age after symptoms appear when a person cannot make enough insulin. However, T1D starts in the body long before any symptoms and can be detected through a blood test. The psychological impact of T1D is hard to quantify, but a diagnosis is life-altering, and regular monitoring and maintenance can be extremely stressful. T1D typically takes more than a decade off a person's life, and life expectancy is reduced by 16 years on average for people diagnosed before the age of 10. Insulin therapy and glucose monitoring are currently the standard of care for treating clinical-stage T1D, and are necessary to keep T1D patients alive. The constant monitoring and administration of insulin represents a significant life-long burden for patients. No disease-modifying treatments for T1D are currently available.