Sargramostim - Leucotropin; granulocyte/macrophage colony stimulating factor, recombinant
Status - approval pending in Canada
Organizations involved:
Cangene Corp. – Manuf.; R&D; Tech.; Intl. mark.
Apotex Holdings Inc. – Parent
Research Corporation Technologies Inc. – Tech.
Cross ref.: See the entry above for Leukine from Amgen.
Description: Leucotropin is a formulation of recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF; sargramostim) produced by bacterial fermentation of Streptomyces lividans bacteria transformed with a plasmid vector containing the human GM-CSF gene. The amino acid sequence of Leucotropin is identical to native human GM-CSF, but it is non-glycosylated. The GM-CSF is monomeric (single-chain) with a theoretical molecular weight of 14,478 Daltons (14.478 kDa) based on the amino acid sequence of the natural molecule. The preparation is sterile and water soluble.
Nomenclature: GM-CSF, rDNA/Cangene [BIO]; Leucotropin [TR]; Sargramostim [FDA]; granulocyte-macrophage colony stimulating factor, recombinant [SY]; rhGM-CSF [SY]
Companies.: Leucotropin is being develop by Cangene Corp. (Winnipeg, Canada). Cangene is majority owned by the Apotex Group, a Canadian company concentrating on generic pharmaceutical development and marketing.
Status: Cangene is developing Leucotropin as a generic (biogeneric, biosimilar, biocomparable follow-on protein, etc.) biopharmaceutical. Cangene will be seeking approvals in countries where lack of patent protection allows. This currently does not include the U.S. or European Union.
Cangene applied for approval in Canada on Oct. 7, 2003, seeking approval “for enhancing recovery of certain white blood cells in patients with Hodgkin’s disease and non-Hodgkin’s Lymphoma following stem cell transplantation.” Leucotropin entered Phase III trials in 1997. I2007, the approval is still pending.
Tech. transfer: Cangene is concentrating on introducing Leucotropin in countries where patents concerning GM-CSF have not issued or patents are not enforced, including many lesser-developed countries (i.e., as a biogeneric, biosimilar, biocomparable, follow-on or other generic biopharmaceutical). GM-CSF-related patents held by Immunex, now Amgen, and others in the U.S., will apparently keep Leucotropin from entering the U.S. and other major markets, at least until these patents expire.
Research Corporation Technologies (RCT) has acquired patents covering the human GM-CSF gene sequence (see the Leukine entry above), and reports that related patents have issued in the U.S., Europe and Australia; and patent applications are pending in Canada and Japan. Presuming, these patents cover Leucotropin, which appears the case, Cangene may have licensed or may need to take a license from RCT to market Leucotropin in territories where RCT holds relevant patents.
Cangene has received U.S. 5,200,327, “Expression system for the secretion of bioactive human granulocyte macrophage colony stimulating factor (GM-CSF) and other heterologous proteins from streptomyces.”
Trials: In Dec. 2005, Cangene reported promising results from a Phase II study with Leucotropin in combination with Rituxan for treatment of relapsed follicular lymphoma.
Market: Although prices have not been announced, it can be expected that, as has been projected for many other generic recombinant proteins, Leucotropin will probably be priced with about a 20-30% discount relative to Leukine from Amgen.
Index Terms:
Companies involvement:
Full monograph
171 GM-CSF, rDNA/Cangene
Nomenclature:
GM-CSF, rDNA/Cangene [BIO]
Leucotropin [TR]
Sargramostim [FDA]
granulocyte-macrophage colony stimulating factor, recombinant [SY]
rhGM-CSF [SY]
FDA Class: Biologic BLA
biopharmaceutical products
Biorex-70 resin
exempt from CBER lot release requirements
growth factors, hematopoietic
recombinant DNA
bacterial culture <!-- bacterialculture -->
streptolysin O
BHK-21 (C-13)
North American coral snake
North American coral snake
EU000 Not yet/Never filed with EU
UM999 Not Available/Not Marketed in US
US000 never filed/no plans
EM999 Not Available/Not Marketed in EU
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