A difficult year for Amgen may be getting worse as EU approvals of two filgrastim biosimilars could mean significant competition in Europe for Neupogen (filgrastim) and Neulasta (long-acting filgrastim), the biopharma's human granulocyte-colony stimulating factor products. The G-CSFs are indicated to treat chemotherapy-induced neutropenia.

Two generic drug makers, Germany's Ratiopharm and Israel's Teva, announced in the past week that they had received marketing approval from the European Medicines Agency for their biosimilars of filgrastim. Ratiopharm plans to launch its Ratiograstim during this year's fourth quarter, while Teva intends to launch TevaGrastim in 2009 (¹ Also see "Teva Expects To Launch First Biosimilar In Europe By Year End" - Pink Sheet, 29 July, 2008.).

This won't be the first time Amgen has faced competition from a biosimilar, or follow-on biologic. The EU previously approved several erythropoiesis-stimulating agents for anemia therapy to compete with Amgen's Epogen (epoetin alfa) and Aranesp (darbepoetin alfa), but Amgen's ESA market share has not been affected greatly to date.

While European Public Assessment Reports (EPAR) for the two new biosimilars have not yet been released, positive opinions issued by EMEA's Committee for Medicinal Products for Human Use in July recommended that Teva and Ratiopharm's filgrastims be approved for reduction in the duration of neutropenia and the incidence of febrile neutropenia in cancer patients undergoing cytotoxic chemotherapy.

CHMP also recommended both be approved to shorten neutropenia duration in bone-marrow transplant patients undergoing myeloablative therapy; to mobilize peripheral blood progenitor cells; to increase neutrophil counts and reduce incidence and duration of infection in children or adults with severe, congenital, cyclical or idiopathic neutropenia; and to treat persistent neutropenia in patients with advanced HIV infection.

Impact could be greater than ESA biosimilars

Asked during the Biosimilars 2008 conference in Washington, D.C., about the potential impact of biosimilars on Neupogen and Neulasta, Thomas Bols, Amgen's director of government affairs, Europe, said he'd have to see the EPARs and find out what indications were approved before making any assessment.

"We've noticed [the approvals]; we will wait for the EPAR to come out to see what are the other characteristics of the products," he told "The Pink Sheet" DAILY. "In terms of the impact, we don't speculate on that. Most importantly, we have full confidence in our own portfolio of Neupogen and Neulasta."

Analyst Christopher J. Raymond of Robert W. Baird, however, expects that filgrastim biosimilars will have a greater toll on Amgen than ESA biosimilars have had. In a Sept. 19 note, Raymond said concerns about pure red cell aplasia (PRCA) held back the growth of ESA competitors but there will be no parallel concerns about biosimilar filgrastim to stifle sales of those products.

While Amgen is taking steps to ameliorate the impact of those competitors, in part by attempting to move Neupogen customers to Neulasta, Raymond predicted an impact on ex-U.S. sales for those two biologics "could become apparent as early as first-half 2009." He projects solid but stagnant ex-U.S. sales for the two Amgen products over the next four years, declining $10 million annually from $1.24 billion this year to $1.21 billion in 2011.

Raymond added that at least one more competitor could enter the EU filgrastim market. Germany's CT Arzneimittel also received a positive opinion from CHMP in July for its Biograstim product, but there has been no EMEA decision on that application to date.

Declining or even stagnating sales of Neupogen/Neulasta would be just another setback for Thousand Oaks, Calif.-based Amgen. The firm experienced flat sales of its ESA products this year while paying $200 million in an antitrust settlement to Ortho Biotech in July over charges it sought to undercut Ortho's ESA Procrit by offering discounted packages of Neupogen, Neulasta and Aranesp to oncology clinics (² Also see "Amgen Seeks To Leave ESA Woes Behind In 2009" - Pink Sheet, 29 July, 2008.).

Ratiopharm and Teva plans

In a release, Ratiopharm said it will sell Ratiograstim "at an affordable price" in "an effort to lower healthcare costs." Approval of its product concludes 10 years of work in biosimilar development, the company said. EU sales will be conducted by direct subsidiaries and by Ratiopharm International.

To meet EMEA's criteria for proving efficacy comparable to Neupogen, Ratiopharm said it tested its product in 880 subjects in Phase I and Phase III trials. Trials involved patients with stage II, III or IV breast cancer, lung cancer or non-Hodgkin's lymphoma being treated with cytostatic chemo. Antibody testing confirmed that Ratiograstim has a comparable immunogenicity profile to the reference product, the firm added.

Teva said it will begin marketing its product throughout Europe next year, adding to the company's previously EU-approved interferon alpha 2b and human growth hormone biosimilars. The company said its "biogeneric pipeline" includes several other products intended for the U.S. and EU markets, although it typically has refused to offer any specifics on those candidates.

-Joseph Haas (j.haas@elsevier.com)

G-CSF Biosimilars Approved By EU Could Impact Amgen Sales

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