Antihemophilic Factor (Recombinant), Formulated with Sucrose - Helixate FS; octocog alfa
Status - approved; marketed
Organizations involved:
Bayer Schering Corp. – Manuf.; R&D; Tech.
Bayer Schering Pharma AG – Parent
CSL Bioplasma Inc. – USA mark.
CSL Behring AG – Tech.; Intl. mark.; Patent dispute; Parent
CSL Ltd. – Parent
Sanofi Aventis S.A. – Tech.; Patent dispute
Behringwerke AG – Tech.; Former
Aventis Behring LLC – Former
Genentech, Inc. – Manuf. other; R&D; Tech.
New York Blood Center, Inc. – Tech.
Synbiotics Corp. – Tech.
Cross ref.: See the Factor VIII Products entry (#715) in the Blood Products, Human section, and the entry for Antihemophilic Factor (Recombinant), Formulated with Sucrose (Kogenate FS) (#149) from Bayer Schering Corp. Helixate FS is Kogenate FS manufactured by Bayer Schering relabeled for marketing by CSL Behring. Note, CSL also markets Bioclate, a different recombinant Factor VIII product manufactured by Baxter.
Description: Antihemophilic Factor (Recombinant), Formulated with Sucrose or Helixate FS is a lyophilized (freeze-dried) formulation of recombinant Factor VIII expressed by baby hamster kidney (BHK) cells, with purification including immunoaffinity chromatography, and solvent/detergent viral inactivation. The recombinant Factor VIII in Helixate FS is a glycoprotein with the same primary sequence as human Factor VIII. The BHK-expressed Factor VIII has the same biologic activity as Factor VIII derived from human serum.
Helixate FS (and the prior Helixate formulation stabilized with human albumin) is manufactured by Bayer Schering (which markets the same product as Kogenate FS), which is relabeled and marketed in the U.S. under the trade name Helixate FS by CSL Behring. Among Factor VIII products, Kogenate FS and Helixate FS have the highest concentration and smallest fluid volume. This reduces the intravenous infusion time, allowing individuals to infuse more rapidly and conveniently.
This product was formerly manufactured by Bayer from Antihemophilic Factor Concentrate (Recombinant) (For Further Manufacturing Use) manufactured by Genentech. Bayer Schering now manufactures the product fully in-house and provides it to CSL Behring for sale under the trade name Helixate FS.
See the Kogenate FS entry for further descriptive information. Like Kogenate FS, upon its original approval, Helixate FS could be stored at room temperature (up to 25˚C) for up to 3 months. However, this was changed in mid-2001 to continuous storage at 2-8˚C (refrigeration).
In Feb. 2007, CSL began U.S. sales of Helixate FS with Mix2Vial, a needle-free transfer device meeting the latest Occupational Safety and Health Administration (OSHA) requirements, along with a 2.5 mL sterile water diluent that can be used for all potencies. Before the Mix2Vial, the reconstitution of Helixate FS required the use of a double-ended transfer needle, which increased patients’ and caregivers’ risk of accidental needlesticks. The Mix2Vial is an easy-to- use, plastic, needle-free transfer device with a built-in filter that works in conjunction with the 2.5 mL diluent to enable fast, easy infusions.
Nomenclature: Factor VIII, rDNA BHK/CSL [BIO]; Helixate [TR prior formulation with albumin]; Helixate FS [TR for current FS formulation]; Helixate NexGen [TR foreign in Europe for Helixate FS]; Antihemophilic Factor (Recombinant) [FDA prior to Helixate FS]; Antihemophilic Factor (Recombinant), Formulated with Sucrose [FDA]; Antihemophilic Factor [USAN]; Antihemophilic Factor, Human [USAN former]; octocog alfa [INN]; Antihemophilic Factor USP [USP]; Blood-coagulation factor VIII, complex [CAS]; 9001-27-8 [CAS RN]; Factor VIII, recombinant [SY]; NDC 0053-8120-01; NDC 0053-8120-02; and NDC 0053-8120-04 [NDC]
Companies.: Helixate FS (and prior Helixate formulated with human albumin as stabilizer) was developed and is manufactured by Bayer Schering Corp. (Berkeley, CA), FDA CBER est. no. 0008, a subsidiary of Bayer Schering Pharma. Helixate was originally manufactured from Antihemophilic Factor Concentrate (Recombinant) (For Further Manufacturing Use) manufactured by Genentech, Inc., CBER/FDA est. no., 1048, but Bayer Schering now fully manufactures and packages the final product for marketing under the trade name Helixate FS by CSL Behring (previously Aventis Behring and Centeon). Product identical to Kogenate FS manufactured (and marketed) by Bayer Schering is relabeled and marketed by CSL Behring under the trade name Helixate FS. Bayer Schering normally shares product with CSL Behring 50-50, but during critical shortages 70% goes to Bayer Schering and 30% to CSL. In April 2005, Talecris Biotherapeutics Inc., then a subsidiary of NPS Pharmaceuticals Inc., acquired Bayer’s plasma products business, but this did not include Bayer’s recombinant hemophilia products.
Helixate is marketed in the U.S. by CSL Bioplasma Inc. (now a subsidiary of CSL Behring AG; formerly Aventis Behring, which was acquired in Dec. 2003, by CSL Ltd. and became ZLB Bioplasma, now CSL Behring), and marketed internationally by CSL Behring AG.
In Feb. 2007, CSL extended its agreement with Bayer (Bayer Schering) for supply of Helixate FS, which will now expire in 2017. The prior agreement was set to expire in 2009
FDA class: Biologic PLA
CBER class: Blood And Blood Derivatives
Approvals: Date = 19930225, first approval, PLA, granted to Bayer Corp. for manufacture of Kogenate (and Bioclate) from Antihemophilic Factor Concentrate (Recombinant) (For Further Manufacturing Use) manufactured by Genentech; Helixate indirectly had orphan status from Kogenate (granted 9/25/1989; expired 2/2000)
Date = 20000628; BLA supplement granted to Bayer; Indication = new formulation and manufacturing processes, including removal of Albumin (Human) as a stabilizer, reformulation with sucrose, addition of solvent-detergent viral inactivation step, improvements in the purification process, and full manufacture within Bayer facilities
Date = 20051007; supplemental BLA; Indication = approval to be stored at room temperature for three months
Date = 2007022; supplemental BLA; Indication = announcement (not approval) of packaging of Helixate with Mix2Vial, a needle-free transfer device and 2.5 mL vial of sterile water diluent that can be used for all potencies
Date = 20090817; supplemental BLA; Indication = routine prophylaxis in children with hemophilia A who are 16 years old or younger and do not have pre-existing joint damage ["approval of Helixate FS for routine prophylaxis"]
Indications: [full text of "INDICATIONS AND USAGE” section of product insert/labeling]:
[Identical to Kogenate FS, except for substitution of HELIXATE for KOGENATE; see relate entry]
Status: Aventis Behring, now CSL Behring AG, received European Union approval for Helixate in August 2000.
Tech. transfer: See the Kogenate FS entry for information about Helixate FS-related patents and technology transfer, including related patent disputes and licensing.
Centeon L.L.C., later Aventis Behring, now CSL Behring, has licensed marketing rights for recombinant Factor VIII manufactured by Bayer Corp.
Market: The 2007 Average Wholesale Price (AWP) is $1.44/IU for all vial sizes (Red Book, 2007). This is unchanged from 2004.
Total worldwide Helixate sales were ~$340 million in 2006
Medicare reimbursement is set at $1.29/IU for inpatient and home care, and $1.01/IU for outpatient care. Estimated Acquisition Costs (for hospitals, treatment centers) is $1.05-$1.09/IU [from NHF].
In its March 22, 2006 price list, FFF Enterprises, a major biologics distributor, reported its price as $0.99/IU (no change from 2005 or 2004).
CSL Ltd. has reported that total sales of Helixate FS were $340 million in FY2006.
In June 2003, Aventis Behring (now CSL Behring) launched the Choice Assurance Program. Enrolled patients earn one Assurance Award Certificate for every three consecutive months they use one of the company’s Factor VIII or IX products or intravenous immune globulin (IVIG). Each Certificate can be redeemed for one month’s worth of free product, in the event of a lapse in insurance. Patients can earn up to four months of free product after only a year in the Program and up to a full year after three years in the Program. At the time, there were no similar programs for Factor VIII in the U.S., although all U.S. marketers have patient assistance programs.
In Aug. 2009, CSL Behring reported that 2.5 billion units Helixate FS had been infused to date.
Companies involvement:
Full monograph
151 Factor VIII, rDNA BHK/CSL
Nomenclature:
Factor VIII, rDNA BHK/CSL [BIO]
Helixate [TR prior to FS]
Helixate FS [TR current FS formulation]
Helixate NexGen [TR foreign in Europe]
Antihemophilic Factor (Recombinant) [FDA prior to FS]
Antihemophilic Factor (Recombinant), Formulated with
Sucrose [FDA]
octocog alfa [INN]
Antihemophilic Factor [USAN]
Antihemophilic Factor, Human [USAN former ]
Factor VIII (rDNA) [BAN]
Antihemophilic Factor USP [USP]
Blood-coagulation factor VIII, complex [CAS]
AHF [SY]
Factor VIII, recombinant [SY]
NDC 0053-8120-01; NDC 0053-8120-02; NDC 0053-8120-04 [NDC]
FDA Class: Biologic PLA BLA
Year of approval (FDA) = 1993
Date of 1st FDA approval = 19930225
(in format YYYYMMDD)
Biosimilars/biobetters-related U.S. Patents: | Note, Helixate, FS marketed in the U.S. by CSL, is the same as Kogenate FS, with Bayer manufacturing Helixate FS for CSL.
2014 (based on 5,668,108 agent patent)
2016 based on 5,763,401 formulation patent |
U.S. Patent Expiration Year: | |
U.S. Biosimilars Data Exclusivity Expiration: | 2005 |
U.S. Biosimilars Orphan Exclusivity Expiration: | 2000 |
U.S. Biosimilars Launchability Year: | 2016 |
U.S. Biobetters Launchability Year: | 2016 |
Biosimilars/biobetters-related EU Patents: | 2017, based on EP 0818204 formulation patent
expired (based on agent patents including EP 0150735, EP 0152746 and EP 0160457) |
EU Patent Expiration Year: | 2017 |
EU Biosimilars Data Exclusivity Expiration: | 2012 |
EU Biosimilars Orphan Exclusivity Expiration: | 2007 |
EU Biosimilars Launchability Year: | 2017 |
EU Biobetters Launchability Year: | 2017 |
Index Terms:
antihemophilic factors
biopharmaceutical products
blood products
bovine materials used<!-- bovinesource -->
exempt from CBER lot release requirements
human materials used<!-- humansource -->
murine (mouse) materials used
recombinant DNA
rodent source materials
baby hamster kidney (BHK) cells
keratinocytes, human
mammalian cell culture
plasma proteins, immunoglobulin-depleted
rodent cells <!-- rodentcells -->
Albumin (Human)
calcium chloride
Factor VIII monoclonal antibodies
glycine
hamster proteins
imidazole
immunoaffinity chromatography
lyophilized (freeze-dried)
monoclonal antibody, Factor VIII x domain
murine monoclonal antibody, Factor VIII
murine proteins
polysorbate 80 (Tween 80)
sodium chloride
Sterile Water for Injection
sucrose
viral inactivation, solvent detergent
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
orphan status
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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