EPO, rDNA/Hexal
Epoetin alfa; erythropoietin, recombinant [biogeneric]
Status: EU biosimilar approval in fall 2007
Organizations involved:
Hexal Biotech Forschungs GmbH –Manuf.; R&D; Tech.
Novartis AG –Intl. mark.; Parent
Cross ref.: See the entries for EPO Products and other EPO product entries
Description: This is a biosimilar (biogeneric; follow-on protein, etc.) version of recombinant erythropoietin (EPO). Presumably, the product was designed to be substantially similar (or be a copy of) Eprex, the brand of r ecombinant human erythropoietin (EPO) glycoprotein expressed by Chinese hamster ovary (CHO) cell culture, incorporating EPO manufactured by Amgen and marketed outside of the U.S. by Ortho/Johnson & Johnson (see the related Epoetin/Procrit and Eprex entries). Presumably, Hexal is using CHO culture to manufacture its EPO.
Nomenclature: EPO, rDNA/Hexal [BIO]; erythropoietin, recombinant [SY]; epoetin alfa [SY]
Companies.: This product was developed and will be manufactured by Hexal (Holzkirchen, Germany). Hexal was acquired by and became a subsidiary of Novartis AG in mid-2005. Note, Sandoz AG, another Novartis subsidiary, has also developed a biosimilar EPO product (see related entry below).
Status: Hexal filed with the European Union (EU) for approval of this product under EU “biosimilar” regulations, which allow abbreviated filings based largely on comparisons, including phamacokinetic/bioavailability trials, with an already-approved product, rather than full, Phase III-like placebo-controlled and other studies.
On June 22, 2007, the Committee for Medicinal Products for Human Use, European Medicines Agency (EMEA), EU, recommended approval of this product. Formal approval is expected later in summer 2007. EMEA review of this and two other biosimilar EPO products (from Medice and Sandoz, see related entries below) began on March 29, 2006, and took 205 days.
EU, approval hase been granted for all Indications: for which the reference EPO (Eprex) is currently approved in the EU. These include the use in treating patients with renal anemia as well as those receiving chemotherapy, but excludes the subcutaneous administration for patients with chronic kidney disease and the use to increase the yield of autologous blood from patients in a predonation program.
Market: In German pharmacies, a package of six 0.5 ml vials dosed 1,000 IU cost 74.21 euros ($105; pharmacy prices), or about $0.0175/IU. This is about 76.4% the cost of Eprex ($0.0229/IU), or ~23.6% discount.
Companies involvement:
Full monograph
134 EPO, rDNA/Hexal
Nomenclature:
EPO, rDNA/Hexal [BIO]
epoetin alfa [SY]
erythropoietin, recombinant [SY]
molecular weight (kDa) = 34
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; expired,
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
EU200 Currently Approved in EU EU777
UM999 Not Available/Not Marketed in US
US000 never filed/no plans
EM001 Marketed Product in EU
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