Epoetin alfa; erythropoietin, recombinant [biogeneric]
Status: EU biosimilar filing abandoned; marketed in Eastern Europe
Organizations involved:
Pliva d.d – Manuf.; R&D; Tech.
Hospira – Parent
Teva Pharmaceuticals – Former
Barr Labs. – Former
Mayne Pharma –R&D; Tech.
Cross ref.: See the entries for Erythropoietin Product, EPO, rDNA/Amgen (Epogen) and EPO, rDNA/Ortho (Eprex).
Description: Epoetin alfa from Pliva, now part of Hospira, was developed to be a biogeneric (biosimilar, biocomparable, follow-on protein, follow-on biologic, etc.) version or copy of Eprex (epoetin alfa) from Ortho/Johnson & Johnson. Thus, it is a liquid formulation of recombinant erythropoietin (EPO) glycoprotein expressed by transformed Chinese hamster ovary (CHO) cells and having the same amino acid sequence as human EPO. The EPO in this product, since it is meant to be a copy of the EPO in Eprex, is essentially identical or substantially similar to EPO in Epogen manufactured and marketed by Amgen in the U.S. for renal disease/dialysis indications:, and marketed by Ortho/J&J as Procrit in the U.S. for other indications:.
Like Eprex, EPO from Pliva is formulated as a sterile, colorless, liquid in an isotonic sodium chloride/sodium citrate buffered solution for intravenous or subcutaneous administration. [It has not been determined whether this product contains Albumin (Human) as a stabilizer, as did Eprex before it exhibited safety-related problems, or not, which would make it more a copy of the current Eprex, but would further raise a number of safety-related issues, e.g., large trials required, that a smaller company like Pliva would be less able to deal with on a scale comparable to Ortho/Johnson & Johnson].
Nomenclature: EPO, rDNA/Hospira [BIO]; Epoetin alfa [INN]; erythropoietin, recombinant [SY]
Companies.: In Feb. 2005, Pliva d.d. (Croatia; acquired by Barr Labs. in late 2006, with Barr later acquired by Teva Pharm., the world's largest generic drug company) formed a collaboration with Mayne Pharma (Australia) for development of biogeneric EPO, with Mayne receiving exclusive marketing rights in Western Europe, N. America, Middle East, and Asia/Pacific, with Pliva retaining other territories, where it was expected to seek other marketing partners. In July 2006, the companies modified their agreement involving both G-CSF and erythropoietin (EPO) in light of the increased clinical program costs brought on by the recent guidelines and scientific advice received from the European Medicines Agency (EMEA), European Union, concerning approval of biosmilars (which upped development costs).
Barr Labs. acquired Pliva in Oct. 2006. Mayne was acquired by Hospira in fall 2006.
Status: In Feb. 2006, Pliva announced it had scaled down its near-term ambitions for development of (i.e., essentially abandoned development in the European Union) its biogeneric/biosimilar EPO product for treatment of anemia in patients undergoing renal dialysis and those undergoing cancer chemotherapy. Pliva stated this was because clinical testing costs for an EU biosimilar filing had increased significantly beyond the scope of the original agreement with Mayne, mainly as a result of the recent biosimilar product guidelines and scientific advice from the European Medicines Agency (EMEA), European Union (the product’s primary target market). Development was halted, despite Pliva’s EPO having encouraging clinical trial results. Pliva reported it was discussing potential alternative collaborations on EPO in Europe with a number of companies.
The product had received approvals in Croatia and, apparently, other Eastern European countries.
Hospira had expected its own biosimilar EPO to be launched in the U.S. in 2012.
Trials: In Aug. 2010, Hospira began a Phase I trial in the U.S. at 20 haemodialysis centers run by DaVita, and Fresenius Medical Care. Pending successful completion of the Phase I trial, Hospira intends to launch an expanded Phase III trial in 2011, and will then presumably file for biosimilar approval.
Market: The author’s rough guess (with no good information to work from) is that sales are meager, perhaps $5-25 million/year.
Companies involvement:
Full monograph
137 EPO, rDNA/Hospira
Nomenclature:
EPO, rDNA/Hospira [BIO]
Epoetin alfa [INN]
erythropoietin, recombinant [SY]
FDA Class: Biologic BLA
Biosimilars/biobetters Data
(Caution: Determining relevant patents, exclusivities and their expirations can be very complex and subjective!
Confirmatory studies are recommended before making business decisions based on these data.
U.S.A.
European Union (EU)
Biosimilars/biobetters-related U.S. Patents: 2013, based on Epogen/Procrit patents; no U.S. approval, no biosimilars possible
U.S. Patent Expiration Year:
U.S. Biosimilars Data Exclusivity Expiration:
U.S. Biosimilars Orphan Exclusivity Expiration:
U.S. Biosimilars Launchability Year:
U.S. Biobetters Launchability Year: 2013
Biosimilars/biobetters-related EU Patents: 2007, year of first approval of EU biosimilars arbitrarily used as expiration date; biosimilar approval, no EU biosimilars possible
EU Patent Expiration Year: 2007
EU Biosimilars Data Exclusivity Expiration:
EU Biosimilars Orphan Exclusivity Expiration:
EU Biosimilars Launchability Year:
EU Biobetters Launchability Year: 2007
Exclusivity add-ons from pediatric and new indication approvals have not been
taken into account. U.S. patent extensions, based on time in clinical trials, have been included, but not those in Europe (where SPCs are individually
issued by each country).
Single year data are presented, but the situation is rarely that simple. This includes determining the relevance of
patents, presuming these have been retrieved, which cna be highly subjective. The first 2 fields for the US and EU are text fields, often
including diverse patent information, including citing other sources' published dates for patent expirations.
Orphan exclusivity is simply 7 years in the U.S. and 10 years in the EU after initial approval, with it left to the user to check monographs for
actual approvals with orphan status. Similarly, data exclusivity expiration in the U.S. is 12 years and in the EU is 10 years after initial reference product
approval, when biosimilar applications can be approved.
 Biosimilars launchability is the latest date of either patent, orphan or data
exclusivity, with any of these blocking approval and/or market entry. Biobetters, by definition products (bio)similar but different enough
to receive full, not biosimilar, approvals, have launchability dates the same as the patent expiration date, with these new/different products
not subject to reference product's orphan or data exclusivity.
Exclusive licensing of patents and other potential factors discussed in the full monographs that could, just as effectively as
patents held by the manufacturer, prevent or confound market entry were included in consideration of patent expiration.
Index Terms:
biopharmaceutical products
Biorex-70 resin
exempt from CBER lot release requirements
hamster source materials
recombinant DNA
Chinese hamster ovary (CHO) cells
rodent cells <!-- rodentcells -->
apheresis (hemapheresis)
BHK-21 (C-13)
North American coral snake
North American coral snake
EU003 EU application withdrawn
UM999 Not Available/Not Marketed in US
US000 never filed/no plans
EM999 Not Available/Not Marketed in EU
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