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RECORD OF TELEPHONE CONVERSATION

Submission Type: BLA    Submission ID: 125402/0    Office: OBRR

Product:
Immune Globulin Infusion (Human), 10% with Recombinant Human Hyaluronidase

Applicant:
Baxter Healthcare Corporation

Telecon Date/Time: 16-Jun-2014 03:30 PM       

Initiated by FDA? Yes

Telephone Number:

Communication Categorie(s):
1. Information Request

Author: CHERIE WARD-PERALTA

Telecon Summary:
Clarification of safety data

FDA Participants: 
Laurence Landow
Cherie Ward-Peralta

Non-FDA Participants: 
Susan O’Brien
Angela Blackshere
Dr. Richard Schiff

Trans-BLA Group: No

Related STNs: None

Related PMCs: None

Telecon Body:
FDA sent the following question to Baxter for discussion during the  telecon 
meeting:

Please provide clarification on the safety data presented on pages 199-239 
(Summary of Number of Subjects with Adverse Events related to IGSC 10% and/or 
rHuPH20 by Age Group and Severity (Studies 160601, 160602, 160603, 170901 Part 4 
and 161001: Safety Analysis Set). There is an apparent discrepancy with respect 
to the Number of Subjects who experienced Mild, Moderate, and Severe Intensity 
Adverse Events, compared with the Total Number (Percent) of subjects listed in 
the far-right column.  For example, the first line listing on page 199 indicates 
8 (57.1%) subjects experienced a Mild AE, 7 (50.0%) subjects experienced a 
Moderate AE, and 2 (14.3%) subjects experienced a Severe AE, yet the Total 
Number of subjects who experienced a Mild, Moderate or Severe AE is only 9 
(64.3%).

Baxter provided the following response within an email sent at 2:23 pm:

We found the example you are referring to on Page 181, Table 15.  We don’t 
believe there is a discrepancy.  Each subject would have had multiple infusions 
and may have had more than one adverse event per infusion; therefore the adverse 
event could be represented in more than one of the severity columns.  For 
example, if there are 6 subjects and each of them had 2 adverse events then the 
total of number of adverse events could be 12 (in the severity columns) but the 
total number of subjects would be 6.

Discussion held within the meeting:
FDA asked why the total number and percent of subjects column was often less 
than the aggregate total of mild, moderate, and severe intensity events. 
Baxter explained that the same subject could have experienced the same event at 
a different intensity but that the subject would be counted only once.

FDA asked whether subjects from study 160601 were recruited into 160603.  Baxter 
replied in the affirmative.  Study 160601 subjects received IVIG for 3 months, 
then 10% IGSC with rHuPR20 for a year.  Three subjects dropped out of the study: 
one had a complication in Epoch 1and  dropped out, and 2 decided not to 
continue.

FDA requested clarification about the table on page 952 presenting nonserious 
AEs stratified by intensity. Baxter indicated that assessment of relatedness and 
intensity is determined by the investigators.  Baxter noted that some of the 
tables from the original submission were revised within the April 2014 
amendment.  The changes included  new data from subjects using the product over 
 3 years for study 160601 and 1.5 years for 160603.

End of Meeting

Another telecon was held on June 23, 2014 to gain additional clarification on 
the following questions sent by email on June 20, 2014:
  In the FSR for Study 160601, a total of SAEs are noted on page 154/6981 and 15 
  SAEs on page 1488/6981.
  In the FSR for Study 160603, the study plan is somewhat opaque. We would 
  appreciate a “walk-through” of the schematic.

Baxter indicated that the 2 related SAEs on page 1488 of 6981 refer to the 
original 2005 pivotal trial 160101, as stated in the appendix of the protocol.  
The study is not part of the BLA, but just background information.  The notation 
is listed on page 26 of the report within the third paragraph.

FDA referred to the schematic for study 160603 and asked whether it was correct 
to conclude that a) Epoch 1 lasted 45 days, b) Epoch 2 lasted 165 days, and that 
c) Arm one in study 160603 included 31 subjects recruited from study 160601 who 
did not receive IVIG.

Baxter stated that this interpretation was  correct and added that  subjects 
received treatment  every 4 or every 3 weeks,  based on their schedule in study 
160601.  Overall, only 16 subjects were treated every 3 weeks whereas the 
majority was treated every 4 weeks. 

FDA asked whether IVIG PK data from 31 subjects in Arm 1 and 56 subjects in Arm 
2 were compared with PK data within the HyQvia arm of study 160603.

Baxter confirmed this essentially was correct, noting some subjects dropped out 
the study.

FDA requested confirmation that the rate of nonserious AEs of mild, moderate and 
severe intensity per infusion in 160603 was slightly lower in the HyQvia cohort, 
although the rate per subject was higher in the HyQvia arm.

Baxter noted that the overall AE rates included local as well as systemic 
events, noting that local mild and moderate AEs were higher in the IGSC arm.

End of Meeting
 

    
 


