Product Approval Information
MEMORANDUM
Department of Health and Human Services
Public Health Service
Food and Drug Administration
Center for Biologics Evaluation and Research
| Date: | 7 January 2008 |
| To: | Jay Epstein, M.D. Director, Office of Blood Research and Review |
| From: | Basil Golding, M.D. Director, Division of Hematology |
| Subject: | Request to waive STN 125264 from referral to Blood Products Advisory Committee |
| CC: | Robert Yetter, Ph.D., Associate Director for Review Management, CBER Diane Maloney, J.D., Associate Director for Policy, CBER |
BACKGROUND
STN 125264 is an original biologics license application (BLA) submitted by Wyeth Pharmaceuticals Inc. (Wyeth) for moroctocog alfa (AF-CC), a recombinant antihemophilic factor (rAHF), under the trade name XYNTHA. The active pharmaceutical ingredient is a recombinant coagulation factor VIII (FVIII) manufactured with modifications to the manufacturing process for ReFacto®, Wyeth's currently licensed rAHF product. The modifications are implemented to eliminate the use of animal- and human-derived proteins in the manufacturing process. The proposed indications for moroctocog alfa (AF-CC), which are the same as those of ReFacto®,: Control and prevention of bleeding episodes and perioperative management of patients with hemophilia A.
REASONS FOR WAIVING REFERRAL TO BPAC
The Division of Hematology in the Office of Blood Research and Review reviewed information from this application and determined that referral to the Blood Products Advisory Committee (BPAC) prior to approval was not needed for the following reasons (FDAAA [HR 3580-138 SEC. 918: REFERRAL TO ADVISORY COMMITTEE]): T6t
- Moroctocog alfa (AF-CC) [XYNTHA] is a recombinant analog of coagulation factor VIII (FVIII). The mechanism of action and function of FVIII in the blood coagulation cascade are well studied and understood.
- XYNTHA is -------------------------------- and structurally similar to Wyeth's currently licensed recombinant FVIII product, ReFacto, licensed on 6 March 2000.
- In vitro and in vivo biochemical and functional characterization demonstrated that XYNTHA is structurally and functionally comparable to its predecessor product, Antihemophilic Factor (Recombinant, B domain deleted) [ReFacto®].
- Pharmacokinetic data show that XYNTHA and Baxter's ADVATE, Antihemophilic Factor (Recombinant), Plasma/Albumin Free Method licensed in 2003, are pharmacokinetically equivalent.
- The results of the pivotal safety and efficacy study did not raise any concerns.
- Review of information submitted in the BLA for XYNTHA did not raise controversial issues or pose unanswered scientific questions which would have benefited from advisory committee discussion and recommendations.
- XYNTHA is considered to have a favorable safety profile related to known infectious agents and impurities.
Letter ready comments that summarize this memo to be included in the approval letter:
We did not refer your application to the Blood Products Advisory Committee because the active ingredient in Antihemophilic Factor (Recombinant), Plasma/Albumin Free [XYNTHA] was shown to be structurally comparable (or similar) to your licensed product Antihemophilic Factor (Recombinant) [ReFacto®,] and pharmacokinetically equivalent to Baxter's ADVATE, Antihemophilic Factor ( Recombinant), Plasma/Albumin Free Method. The mechanism of action and function of FVIII in blood coagulation is well understood. Our review of information submitted in your BLA, including the clinical study design and trial results, did not raise concerns or controversial issues which would have benefited from an advisory committee discussion
.