Information Request Email, March 1, 2013 - ALPROLIX	

From: Thompson, Edward
Sent: Friday, March 01, 2013 9:24 AM
To: 'Nadine D. Cohen PhD (nadine.cohen@biogenidec.com)'
Cc: Debra Segal; Staschen, Carl-Michael; Kirschbaum, Nancy (Nancy.Kirschbaum@fda.hhs.gov)
Subject: Information Request for BL 125444/0

Contacts: Nadine D. Cohen PhD

Dear Dr. Cohen:

We are reviewing your December 28, 2012 biologics license application (BLA) for Coagulation Factor IX (Recombinant), Fc Fusion Protein. We are providing the following comments and request for additional information to continue our review:

Clinical Pharmacology

Regarding Phase 3 clinical study No. 998HB102
1.Please provide a summary table of all six 50 IU/kg dose PK studies in the four arms. The PK parameter summary table should include the arithmetic mean, calculated from all six trials, followed by the coefficient of variation (CV%) and the 95% confidence interval in parenthesis: Cmax, AUCinf, CL, V1, Vss, half-life (alpha), half-life (beta), MRT, IR, time to 1% FIX activity, and time to 3% FIX activity.
2.Please provide six separate figures of rFIXFc concentration-time plots of the six 50 IU/kg PK studies in the four study arms. Each plot should include mean concentration data with standard error on both sides, and the predicted curve based on the 2- compartment analysis.
3.Please provide one rFIXFc concentration-time plot including all six 50 IU/kg dose PK studies. The graph should display mean concentration data and standard error on both sides, color coded by trial.

The review of this submission is ongoing and issues may be added, expanded upon, or modified as we continue to review this submission.

Please submit your response to this information request as an amendment to this file by March 15, 2013 referencing the date of this request. If you anticipate you will not be able to respond by this date, please contact the Agency immediately so a new response date can be identified.

The action due date for this file is December 28, 2013.

Please send an acknowledgement message to me for receipt of this request.

If you have any questions, please contact me at (301) 827-9167.


Sincerely,

Edward Thompson
 Regulatory Project Manager
 FDA/CBER/OBRR/DBA/RPMB

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