Spectrum Pharmaceuticals, Inc. has received marketing approval from the US 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, 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 commercialisation".
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, 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. Levoleucovorin is a novel folate analog formulation and the pharmacologically active isomer of calcium leucovorin. Levoleucovorin 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). Upon market launch, Levoleucovorin will be supplied in 50mg vials of freeze-dried powder. Ex-US sales of Levoleucovorin by Wyeth, Sanofi-Aventis, and others, are approximately $200 million annually.
Levoleucovorin is contraindicated for patients who have had previous allergic reactions attributed to folic acid or folinic acid. Due to calcium content, no more than 16mL (160mg) of Levoleucovorin for Injection solution should be injected intravenously per minute. Levoleucovorin for Injection enhances the toxicity of fluorouracil. Concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in HIV patients was associated with increased rates of treatment failure in placebo-controlled study. Allergic reactions were reported in patients receiving Levoleucovorin for Injection. Vomiting (38 per cent), stomatitis (38 per cent) and nausea (19 per cent) were reported in patients receiving Levoleucovorin for Injection as rescue after high dose methotrexate therapy. Levoleucovorin for Injection may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible patients.