Alternative to Amgen’s Neupogen Ready to Launch

Filgrastim stimulates the production of neutrophils, a type of white blood cells important in the body’s fight against infection. One treatment option for individuals with certain types of cancers is myelosuppressive chemotherapy which targets rapidly dividing tumor cells. Since rapidly dividing normal cells, such as bone marrow precursor neutrophils are also vulnerable to the cytotoxic effects of myelosuppressive chemotherapy, lower numbers of neutrophils are produced, a condition called neutropenia, which increases the risk of severe infection. Amgen launched filgrastim, under the Neupogen brand, in 1991 to decrease the incidence of infection, as manifested by febrile neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Dr. Karl Welte is the researcher who discovered neupogen (GCSF).   Dr. Welte has been a major advocate for Ariana-Leilani to receive life saving GCSF to save her life.

Since Amgen’s principal European patent related to filgrastim was due to expire in August 2006, the company launched a long acting formulation, a pegylated filgrastim (pegfilgrastim), under the brand name Neulasta in 2002. The move, part of Amgen’s product lifecycle management strategy, resulted in Neulasta replacing Neupogen in major treatment centers. Amgen’s US patent for Neupogen expires in December 2013. Although Neulasta’s patent does not expire until December 2015, the launch of generic competition could adversely affect sales of both brands.

Teva is a serious player in the international biosimilars market. Teva also has two long acting filgrastim formulations in late stage development.  In August 2012, the FDA approved Teva‘s (TEVA) Neutroval (tbofilgrastim). The approval, which was based on a full Biologic License Application (BLA) rather than under the FDA’s new biosimilar approval pathway, would allow Teva to compete directly with Amgen‘s (AMGN) US filgrastim franchise, worth $4.2 billion at the end of 2012. However, due to a court ruling related to Amgen’s filgrastim patents, Teva may not start selling its product in the US until the 10th of November 2013, in just six weeks’ time.  Read More: Seeking Alpha

Colony-Stimulating Factors for Febrile Neutropenia

Responses of the Authors:

Ishiguro and Toi and Kelly et al. question the wisdom of universal adherence to the 6-mg, fixed-dose formulation of pegfilgrastim currently approved by the Food and Drug Administration. Citing the pharmacokinetic data and preliminary clinical data, Ishiguro and Toi suggest that the most appropriate dose in Japanese patients should be 3.6 mg per cycle of chemotherapy and not the currently approved dose of 6 mg per cycle. Kelly et al. justifiably raise the issue of costs associated with the administration of CSF. They cite a small, nonrandomized, preliminary study suggesting that half-dose pegfilgrastim may be as effective as the standard 6-mg dose and potentially associated with less pain. Although we are sympathetic to these arguments, we also think that larger and more definitive studies should be conducted before the current package label is changed.

Buti et al. raise the issue of discrepancy in the literature, with some meta-analyses showing no effect of CSF on rates of infection-related death and overall survival, whereas others apparently do. Many factors can lead to discordant meta-analyses,1 the most common being the number and type of the studies selected for the meta-analysis, as Buti and colleagues indicate. The studies by Kuderer et al.2 and Lyman et al.3 showing that the use of CSF is associated with reduced mortality were more selective in scope and included far fewer patients and studies than did more comprehensive meta-analyses showing no such association in the context of either prophylaxis4 or treatment.5

Carton et al. outline a rare, but important, complication related to the management of breast cancer during pregnancy and provide their rationale for why the use of CSF should be avoided in pregnancy.

Benjamin Djulbegovic, M.D., Ph.D.
University of South Florida, Tampa, FL

LeAnn B. Norris, Pharm.D.
Charles L. Bennett, M.D., Ph.D.
University of South Carolina, Columbia, SC
bennettc@sccp.sc.edu

Read More: GCSF

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Neulasta significantly reduced the incidence of febrile neutropenia,

Neulasta significantly reduced the incidence of febrile neutropenia, which is low white blood cell count combined with fever. The drug more than halved the percent of chemotherapy patients contracting grade 3 or 4 febrile neutropenia as compared to a placebo group, the company said, cutting the incidence from 5.7% to 2.4%.

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