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.