Anti-hemophilic factor (recombinant), plasma/albumin-free method (octocog-alpha; ADVATE^®) in the management of hemophilia A

Figures & data

Table 1 Commercial recombinant FVIII therapies

Generation	Product	Producing cell line	Culture medium	Molecular FVIII	Product stablizer
First	Recombinate^®	CHO	Bovine serum albumin	Full-length	Human albumin
Second	Kogenate^® FSb	BHK	HPPSa	Full-length	Sucrose
Second	Helixate^® FSb	BHK	HPPSa	Full-length	Sucrose
Second	ReFacto^®	CHO	Human serum albumin	B-domain deleted	Sucrose
Third	ADVATE^®	CHO	None	Full-length	Trehalose

CHO indicates Chinese hamster ovary cell line; BHK indicates Baby hamster kidney cell line. Information as indicated in respective product package inserts.

a HPPS, Human plasma protein solution consists of several human plasma proteins, including albumin.

b The equivalent products Kogenate FS and Helixate FS are also marketed under the brand names Kogenate Bayer and Helixate Nexgen, respectively.

Table 2 Global clinical program of ADVATE^®

Study (n)	Endpoints
Pivotal (108)	Pharmacokinetics, efficacy, safety and immunogenicity in PTPs
Continuationa (82)	Long-term pharmacokinetics, efficacy, safety and immunogenicity in PTPs who completed the Pivotal study
Surgerya (59)	Efficacy and safety in PTPs undergoing surgical/invasive procedures
Pediatric (53)	Pharmacokinetics, efficacy, safety and immunogenicity in PTPs <6 years old
Japanese Registry (15)	Pharmacokinetics, efficacy, safety and immunogenicity in PTPs in Japan

a Patients were eligible to participate in more than one study

Abbreviations: PTPs, previously treated patients.

Figure 1 PK comparisons of Recombinate^® and ADVATE^®. Post-infusion factor VIII levels (logarithmically adjusted for illustrative purposes) over time were similar with R-FVIII and ADVATE^®. Data shown represent the natural logarithm FVIII activity (Ln) as a function of time in hours (h). Reprinted with permission from Tarantino MD, Collins PW, Hay CR, et al 2004. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia, 10:428–37. Copyright © 2004 Blackwell Publishing.

Figure 2 Mean annual total bleed episode rate per regimen. Subjects on prophylactic regimens experienced fewer bleeding episodes than those using on-demand treatment.

Table 3 Predicted and actual blood loss associated with surgical procedures

Procedure	Actual blood loss (mL)	Average-maximum Predicted blood loss (mL)
Ross procedure	50	200–2000
Axillary mass excision	50	N/D
Arthroscopie knee synovectomy	50	50–250
Port-a-cath removal	100	15–50
Port-a-cath removal and excision of seroma	8	5–10
Elbow synovectomy	20	30–100
Inferior oblique myectomy	0	0.5–1.0
Arthroscopic ankle synovectomy/debridement	5	10–50
Radionuclide ankle synovectomy	0	0
Dental extraction	15	5–15
Multiple teeth extraction (a)	5	5–10
Multiple teeth extraction (b)	7	20
Eye cyst excision	1	2
Central catheter removal (a)	5	5
Central catheter removal (b)	20	15–20

N/D, Not documented.

Figure 3 Global clinical program study plan. Five Phase II/III clinical studies have been completed (dark bars), while four additional Phase IV studies are in progress as of 2007 (hatched bars).

EwensteinBMCollinsPTarantinoMDHemophilia therapy innovation: development of an advanced category recombinant factor VIII by a plasma/albumine-free methodSemin Hematol2004411, Suppl 211815071785

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