Coagulation Factor IX (Recombinant) - IB1001; OBI-1 Antihemophilic factor B; rFIX; nonacog alfa
Status - BLA approved in June 2013
Organizations involved:
Cangene Corp. – R&D; Tech.; World mark.
CMC Biopharmaceuticals A/S – Manuf.
Inspiration Biopharmaceuticals, Inc. – R&D; Tech.; Former
Ipsen S.A. – World mark.; Former
Cross ref.: See the Factor IX Products entry in the Blood Products section for further information about Factor IX. See also the entry for BeneFIX.
Description: Coagulation Factor IX (Recombinant) or IBoo1 is a formulation of nonacog alfa, a purified recombinant human Factor IX single-chain glycoprotein, presumably expressed by a transformed Chinese hamster ovary (CHO) cell line.
Nomenclature: Factor IX, rDNA/Ipsen [BIO]; Coagulation Factor IX (Recombinant) [FDA]; Rixubis [Sy]; nonacog alfa [USAN INN]; Antihemophilic Factor IX [SY]; Factor IX [SY]; IB001 [SY]; rFIX [SY]
Companies.: In Jan. 2010, Inspiration and Ipsen entered into a strategic partnership to develop and commercialize hemophilia products. This included Inspiration in-licensing OBI-1/IB001 from Ipsen, as well as Ipsen providing Inspiration with milestone-based funding to support the development of Inspiration's two lead development programs. Based on the terms of this partnership, Inspiration will receive a $35 million milestone payment from Ipsen associated to the filing of the IB1001 BLA. In return, Inspiration will issue a convertible note to Ipsen, bringing Ipsen's fully diluted equity ownership position in Inspiration to approximately 43.5%.
In Sept., 2011, CMC Biologics, a major contract manufacturer, and Inspiration Biopharmaceuticals entered into a long-term commercial supply agreement for the manufacture of bulk IB1001. CMC Biologics will be the exclusive manufacturer of bulk IB1001 for at least six years. CMC Biologics expected commercial supply manufacturing to begin in fall 2011. It was not disclosed whether the product will be manufactured in CMC facilities in Copenhagen, Denmark, or Seattle, WA.
In Aug. 2012, Inspiration and Ipsen renegotiated their 2010 strategic partnership agreement. Ipsen recovered commercial rights to OBI-1, while Inspiration remained responsible for the world-wide development of OBI-1 (and IB1001). Ipsen will record sales.
In Inspiration’s territories, Ipsen will receive a mid-twenties royalty on sales of OBI-1.
As part of the renegotiation, Ipsen paid Inspiration $30.0 million upfront. Including this upfront payment, Ipsen was entitled to pay Inspiration milestones for a total amount of up to $200m, of which $27.5m are regulatory milestones and the remaining are commercial milestones. Both companies believe this new agreement will facilitate Inspiration’s ability to raise independent third party financing to meet its financing needs until a potential equity offering in 2013. Ipsen agreed to invest up to $20.0 million in Inspiration.
In Nov. 2012, after the FDA hold on IB1001 (see below) and OBI-1 (recombinant porcine Factor VIII) stayed in place, Inspiration filed for Chapter 11 bankruptcy protection and prepared for a sale of its assets through the courts. Ipsen then owned 40% of the company, and $200 million in convertible bonds make it the only senior secured debt holder.
In Feb. 2013, Cangene Corp. acquired IB1001 and other assets from Ipsen and Inspiration Biopharmaceuticals, Inc. in connection with Inspiration's bankruptcy proceedings. Under the terms of the agreement, Cangene paid approximately $5.9 million upfront for IB1001 and other acquired assets, and pays tiered royalties on net sales and additional payments, if certain sales milestones are achieved.
Status: On April 17, 2012, Inpiration filed a BLA for or the treatment and prevention of bleeding in individuals with hemophilia B.
Inspiration's Marketing Authorization Application (MAA) for IB1001 was accepted by the European Medicines Agency in Sept. 2011
In July 2012, FDA imposed a hold on two late-stage trials of IB1001 after Inspiration Biopharmaceuticals reported that patients had developed antibodies (inhibitors), despite no adverse events having been linked to the antibodies. While no relationship had been observed to date between the host cell protein reactivity and the development of any antibodies to FIX or with the adverse event profile in patients, the clinical hold impacted two ongoing IB1001 Phase 3 clinical trials. In Feb. 2013, based on recent communications with the FDA, Cangene reported that additional IB1001 manufacturing and development information will be required for the BLA.
Tech. transfer: Apparently, sufficient patents covering recombinant Factor IX have expired, allowing development of IB1001.
Trials: The IB1001 BLA filing includes a comprehensive set of pharmacokinetics, safety and efficacy data from a Phase III clinical trial in patients affected by hemophilia B. A surgery substudy was also included.
IB1001 was well tolerated by patients in its pivotal Phase III testing and pharmacokinetic results have demonstrated non-inferiority to BeneFIX, the only approved recombinant FIX product currently available for the treatment of hemophilia B.
Companies involvement:
Full monograph
144.1 Factor IX, rDNA/Inspiration
Nomenclature:
Rixubis []
Factor IX, rDNA/Ipsen [BIO]
Coagulation Factor IX (Recombinant) [FDA]
nonacog alfa [USAN INN]
Antihemophilic Factor IX [SY]
Factor IX [SY]
IB1001 [SY]
rFIX [SY]
FDA Class: Biologic BLA
Year of approval (FDA) = 2013
Date of 1st FDA approval = 20130627
(in format YYYYMMDD)
Index Terms:
antihemophilic factors
biopharmaceutical products
Biorex-70 resin
blood products
exempt from CBER lot release requirements
hamster source materials
recombinant DNA
Chinese hamster ovary (CHO) cells
mammalian cell culture
rodent cells <!-- rodentcells -->
Biorex-70 resin
EU002 EU application pending
UM001 Marketed Product in US
US200 Currently Approved in US
EM999 Not Available/Not Marketed in EU
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