Drugs Log

Spectrum Pharmaceuticals, Inc. today announced that it has received marketing approval from the U.S. Food and Drug Administration (FDA) for Levoleucovorin for Injection. It is indicated after high-dose methotrexate therapy in patients with osteosarcoma, and to diminish the toxicity and counteract the effects of impaired methotrexate elimination or inadvertent overdose of folic acid antagonists. LEVOleucovorin is the only commercially available formulation comprised only of the pharmacologically active enantiomer of leucovorin (Levoleucovorin or (6S)-leucovorin). The Company currently expects its commercial launch by June 2008.

LEVOleucovorin was reviewed under a full NDA, and included an Oncologic Drug Advisory Committee (ODAC) review. Spectrum anticipates that the drug will be listed without any therapeutically equivalent product in the FDA Orange Book. Drugs without therapeutic equivalents are considered ’single source drugs’ which under section 1847A of the Social Security Act generally qualify for a separate reimbursement code with CMS.

“LEVOleucovorin is the first new oncology drug approved by the FDA in 2008, and is the first of what we hope will be many approvals from our pipeline,” said Rajesh C. Shrotriya, M.D., Chairman, President and Chief Executive Officer of Spectrum Pharmaceuticals. “Only four of the 17 drugs approved by the FDA in 2007 were new oncology drugs. This approval is the result of dedicated efforts by our experienced team and serves as a validation of our business model. We are focused on building a diversified portfolio of promising late stage drugs, and advancing them through clinical development, regulatory process and commercialization.”

In preparation for the commercial launch, last year the Company appointed George Uy, an experienced oncology marketing veteran, as its Vice President of Sales and Marketing. George brings more than 20 years of hands on experience, including the launches of ABRAXANE® at Abraxis Bioscience, Inc., and XELODA® at Hoffmann-La Roche Inc. In addition, the Company recently appointed Lynne Murphy as Executive Director of Sales. Ms. Murphy has more than 20 years of sales and marketing experience, which include many sales leadership positions with responsibility for the launch of more than 10 products during her tenure at Bayer Healthcare. Ms. Murphy also led a specialty sales force for Amgen, Inc., and launched Aranesp® Singleject. Ms. Murphy will be responsible for building and assembling a launch team of experienced oncology sales specialists.

“LEVOleucovorin provides physicians and patients with an important treatment alternative to leucovorin,” said Richard A. Bender, M.D., F.A.C.P., Chief Medical Officer of Spectrum Pharmaceuticals. “With this drug, patients undergoing cytotoxic chemotherapy are spared the administration of the pharmacologically inactive dextro-isomer. Preclinical studies have shown that the dextro-isomer may compete with the active levo-isomer for transport into cells.”

The Company plans to file for a supplemental New Drug Application with the FDA for use in colorectal cancer in 5-fluorouracil containing regimens and an NDA amendment for an oral tablet formulation by mid-year 2008.

Levoleucovorin for Injection is currently listed as a replacement for calcium leucovorin in the NCCN Clinical Practice Guidelines in Oncology. The NCCN Drugs and Biologics Compendium is an important reference that has been recognized by United HealthCare as a formal guidance for approval of coverage policy. Visit www.nccn.org for more information.

Calcium levofolinate (calcium levoleucovorin/levofolinic acid)

How does it work?

This medicine contains the active ingredient calcium levofolinate, also known as calcium levoleucovorin. It is the calcium salt of a vitamin called levofolinic acid, which is related to folic acid. It is usually referred to simply as folinic acid.

Levofolinic acid is a vitamin that has two main uses. Firstly, it is used to reduce the side effects from high doses of the anticancer medicine methotrexate. Secondly, it is used in combination with the anticancer medicine fluorouracil (5-FU), as it has been shown to boost the response rate to this anticancer medicine.

In cancer treatment with the chemotherapy medicine methotrexate, calcium levofolinate is given for ‘folinic acid rescue therapy’. It helps healthy cells recover from the effects of the methotrexate.

Methotrexate works by blocking the action of an enzyme in the body called dihydrofolate reductase. Cancer cells in the body use this enzyme to convert folic acid consumed in the diet into tetrahydrofolic acid. They then use tetrahydrofolic acid to make new genetic material, which allows the cancer cells to grow and multiply. However, healthy body cells also use this enzyme to make tetrahydrofolic acid. So while methotrexate can stop cancer cells from producing tetrahydrofolic acid to grow and multiply, it also has the same effect in healthy body cells. This is what causes the side effects of the chemotherapy, for example, decreased numbers of white blood cells.

Levofolinic acid is a derivative of tetrahydrofolic acid and is usually given 24 hours after the methotrexate. It doesn’t need to be converted by dihydrofolate reductase to be used by the body cells, so it bypasses the action of the methotrexate and allows the cells to grow and multiply again. Normal healthy cells recover faster than cancer cells and this helps to prevent the side effects of the methotrexate. The aim is to progressively shrink the cancer over several cycles of chemotherapy, allowing normal healthy cells to recover in between.

Fluorouracil (5-FU) is a chemotherapy medicine that works in a different way to methotrexate. It reacts with tetrahydrofolate inside cells and forms a complex that is harmful to the cells. Levofolinic acid is used in combination with 5-FU to increase the amount of tetrahydrofolate inside the cells and therefore boost the effect of the 5-FU. It has been shown to boost the effectiveness of 5-FU in the treatment of advanced colorectal cancer.

Levofolinic acid is given in the form of calcium levofolinate as an injection into a vein or muscle.

What is it used for?

• Enhancing the effect of the chemotherapy medicine fluorouracil (5-FU) in treating advanced colorectal cancer
• Reducing the side effects of the chemotherapy medicine methotrexate

Warning!

When taken for folinic acid rescue therapy this medicine should not be taken simultaneously with the methotrexate, as the medicines may then cancel out each others effects.