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Record of Telephone Conversation, May 31, 2013 - RIXUBIS
Submission Type: BLA Submission ID: 125446/0 Office: OBRR
Product: Coagulation Factor IX (Recombinant)
Applicant: Baxter Healthcare Corporation
Telecon Date/Time: 31 May 2013, 12:00 PM Initiated by FDA? Yes
Communication Category: 1. Advice
Author: Edward Thompson
Revised: Nisha Jain
Telecon Summary: To discuss future Post Marketing Commitments (PMC) by Baxter
Nisha Jain, MD, Chief, OBRR/DH/CRB
Tim Lee, PhD, Acting Chief, OBRR/DH/LH
Mikhail Ovanesov, PhD, OBRR/DH/LH
Stephanie Omokaro, MD, OBRR/DH/CRB
Edward Thompson, OBRR/DBA/RPMB
Baxter Healthcare Corporation
Kevin Smyth, Associate Director, Global RA
Erik Bjornson, Director, Global RA
Mehrshid Alai, Senior Director, Global RA
Doug Hunt, VP, Global RA
Wing Wong, Senior Medical Director, Hemophilia
Thomas Soucek, Senior Project Manager
This teleconference was initiated by the FDA to discuss PMCs for this application. The focus of the teleconference is to establish a PMC to collect data for efficacy and safety purposes. In terms of safety, the proposal is focus on collecting additional information on inhibitors, non-neutralizing FIX-binding antibodies, anti-CHO and anti-Furin antibodies.
Baxter proposed that data for the requested PMC could be obtained through the on-going pediatric, surgical and continuation studies that are projected to be completed by 2015 (2 year follow-up).
FDA requested that Baxter submit an amendment to the continuation study that would allow expansion of the current study with 25 newly enrolled subjects and a total of 100 hemophilia B subjects of all ages. The study would be conducted globally.
Baxter was concerned about recruitment challenges for this number of participants.
FDA responded to Baxter’s concerns regarding recruitment with a plan to provide continued guidance through regular communications and re-evaluations of the study protocol. Baxter agreed to the plan.
Baxter proposed using health-related quality-of-life scale as the primary endpoint for the PMC given expected difficulties with recruitment. FDA responded that quality-of-life measurements are typically difficult to achieve as endpoints because they require the pre-defined changes from baseline be achieved and reached statistical significance.
FDA suggested that the primary endpoint continue to be data pertaining to long-term efficacy with secondary endpoints focused on the safety parameters of inhibitors, FIX-binding antibodies, anti-CHO and anti-Furin antibodies.
In addition to the general plan for the proposed PMC, FDA requested Baxter to include with the PMC proposal the dates for protocol submission, study/trial completion and final report submission.
FDA introduced the CMC PMC to provide validation data to support the Precision (Repeatability and Intermediate Precision), Linearity and Range for the assayused to determine the dimmers—b(4)----------------------- in RIXUBIS. The proposed timeline would be 3-6 months. In addition, FDA proposed to formalize Baxter’s stability study commitments as a PMC. FDA will forward the PMC proposal in an information request for Baxter’s agreement.
FDA also conveyed the on-going negotiation for the package insert (PI). An information request will be sent out in the next few business days. FDA was concerned with the language for the b(4) year old age group categorization as this population is already included in the definition for adults. FDA also informed Baxter that historical data from a published clinical study is not allowed in the PI.
FDA requested the revised PI and proposed plan for the PMCs be submitted by the following week with Friday, June 7th as the latest date.
Baxter asked if the proposed shelf-life of 18 months is acceptable. FDA indicated that it is acceptable.