Information Request, September 16, 2013- Eloctate

DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service

Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448

 

Our Reference:  BL 125487/0

Biogen Idec Inc.
Attention:  Ms. Debra Segal
September 16, 2013
Sent by email

Dear Ms. Segal:

We are reviewing your March 7, 2013 biologics license application (BLA) for Antihemophilic Factor (Recombinant), Fc Fusion protein.  We are providing these comments and request for additional information to continue our review:

Regarding  :           1.         Pharmacometric Study Report (CPP-12-026-BIIB031)
                       2.         1.11.3 Efficacy Information Amendment (Response to FDA Request for Information) Table 2 and Table 5

In the Pharmacometric Study Report (Table 1, p.65) the applicant reports the primary parameters of the final population PK model for rFVIIIFc (F82fin0F17).

We calculated the terminal half-life (HL_beta) based on the final population model parameters (F82fin0F17) to be HL_beta = 68.1 hours. Please explain the major discrepancy between the population analysis based terminal half-life and the reported terminal half-lives (Table 5) of the Phase 1/2a study (19.2 hr. for the 25 IU/kg dose group and 19.8 hr. for the 65 IU/kg dose group) and of the Phase 3 study (19.7 hr. for the 50 IU/kg dose group).

Note, the post-hoc calculated terminal half-life of AdvateŽ based on the results of the population PK model for AdvateŽ AdvOD (HL_beta = 12.2 hr.) is similar to the reported terminal half-life (Table 2) of the Phase 3 study (12.91 hr.).

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

Please submit your response by September 19, 2013, referencing the date of this request.

The action due date for this file is March 8, 2014.

If you have any questions, please contact me at (301) 827-6116.

Sincerely,

Leigh Pracht
Regulatory Project Manager
FDA/CBER/OBRR/DBA/RPMB