These drugs recently received final approval from the U.S. Food and Drug Administration (FDA):
• Tositumomab and Iodine I 131 Tositumomab (Bexxar) by Corixa and GlaxoSmithKline. The FDA has approved tositumomab and iodine I 131 tositumomab (Bexxar) for the treatment of patients with CD20-positive, follicular, non-Hodgkin’s lymphoma (NHL), with and without transformation, and whose disease is refractory to rituximab and has relapsed following chemotherapy.
Tositumomab and iodine I 131 tositumomab is a dual-action therapy that pairs the tumor-targeting ability of a cytotoxic monoclonal antibody (tositumomab) and the therapeutic potential of radiation (Iodine-131) with patient-specific dosing.
Combined, these agents form a radiolabeled monoclonal antibody (Iodine I 131 Tositumomab) that is able to bind to the target antigen CD20 found on NHL cells, thereby initiating an immune response against the cancer and delivering a dose of radiation directly to tumor cells.
The efficacy of the therapeutic regimen was examined in a multicenter, single-arm study of 40 patients with follicular NHL whose disease had relapsed following or had not responded to treatment with rituximab. (The therapeutic regimen consists of four components administered in two steps over seven to 14 days, usually on an outpatient basis.)
In patients with rituximab-refractory disease, 63% of patients had a response to tositumomab and iodine I 131 tositumomab, with a median duration of response of 25 months. Twenty-nine percent of patients had a complete response (no clinical signs of disease) to the therapy. The median duration of complete responses has not been reached after a median follow-up of 26 months.
The results of this study were supported by demonstration of durable objective responses in four other single-arm studies enrolling 190 patients with rituximab-naive, follicular NHL, with or without transformation, who had relapsed following or were refractory to chemotherapy. In these studies, the overall response rates ranged from 47% to 64% and the median durations of response ranged from 12 to 18 months.
The most common adverse reactions occurring in the clinical trials included neutropenia, thrombocytopenia, and anemia that can be both prolonged and severe. The most common nonhematologic side effects included asthenia (weakness), fever, nausea, infection, and cough.
• Omalizumab (Xolair) by Genentech. The FDA has approved the first biotechnology product to treat patients with a type of asthma that is related to allergies.
The product, omalizumab (Xolair), is a monoclonal antibody that has been shown to be safe and effective to treat people 12 years of age and older with moderate-to-severe allergy-related asthma inadequately controlled with inhaled steroid treatments. (The product’s labeling states that this type of asthma should be established by skin or blood test before treatment.)
In these patients, omalizumab has been shown to decrease the number of asthma exacerbations or episodes of airway narrowing that result in wheezing, breathlessness, and cough. The product is given as an injection under the skin.
During the clinical trials, more patients treated with omalizumab developed a new or recurrent cancer (0.5%) compared to control patients (0.2%). The sponsor is planning long-term studies in an attempt to determine whether there is a relationship between omalizumab treatment and cancer. The other major safety concern with omalizumab identified in the clinical trials was severe allergic reactions or anaphylaxis. Anaphylaxis occurred in three patients; all responded to and recovered following medical treatment.
• Atazanavir sulfate (Reyataz) by Bristol-Myers Squibb Co. The FDA has approved atazanavir sulfate (Reyataz), a protease inhibitor to be used in combination with other antiretroviral agents for the treatment of patients with HIV infection. Approval of this drug will now allow patients access to a protease inhibitor that only needs to be taken once daily with food and has a low "pill burden" (two pills each day).
A significant safety concern commonly observed with the use of protease inhibitors is hyperlipidemia (high cholesterol). Atazanavir sulfate appears to have minimal impact on lipid parameters such as triglycerides and cholesterol.
The most common laboratory abnormality observed with the use of atazanavir sulfate is hyperbilirubinemia. This laboratory abnormality resulted in the clinical adverse event of jaundice (yellowing of the skin) or scleral icterus (yellowing of the eyes) in 15%-24% of subjects taking atazanavir sulfate.
This abnormality was shown to be reversible upon discontinuation of the drug. Hyperbiliru-binemia with atazanavir sulfate did not appear to be associated with an increased risk of liver injury.
The most frequently reported adverse events among patients in the clinical trials were nausea, infection, headache, vomiting, diarrhea, abdominal pain, somnolence (drowsiness), insomnia, and fever.
• Influenza Virus Vaccine Live, Intranasal (FluMist) by MedImmune Vaccines. The FDA has approved the first nasally administered influenza vaccine to be marketed in the United States. It also is the first live virus influenza vaccine approved in the country.
FluMist is approved to prevent influenza illness due to influenza A and B viruses in healthy children and adolescents, ages 5 to 17 years, and healthy adults, ages 18-49. Children 5 to 8 years old need two doses at least six weeks apart in their first year of influenza vaccination with FluMist, and individuals 9 to 49 years old need one dose.
Each dose of FluMist is formulated to contain each of the three influenza virus strains recommended by the U.S. Public Health Service for the 2003-2004 influenza season: two strains of influenza A, which causes the most severe and widespread outbreaks, and one strain of B, which usually causes a more mild illness.
In a large safety study, children younger than age 5 were found to have an increased rate of asthma and wheezing within 42 days of vaccination compared to placebo recipients. For people age 50 years and older, the safe and effective use of FluMist also has not been established.
The most common adverse events associated with the vaccine were nasal congestion, runny nose, sore throat, and cough.
• Copackaged pravastatin sodium and buffered aspirin tablets (Pravigard PAC) by Bristol-Myers Squibb Co. The FDA has approved copackaged pravastatin sodium and buffered aspirin tablets (Pravigard PAC) for use when treatment with both pravastatin (Pravachol) and buffered aspirin is appropriate. This copackaged product may be more convenient for some patients.
Pravastatin and buffered aspirin are both indicated to reduce the occurrence of cardiovascular events, including death, myocardial infarction, or stroke, in patients who have clinical evidence of cardiovascular and/or cerebrovascular disease. Patients receiving treatment with the copackage also should be placed on a standard cholesterol-lowering diet.
The usual dose of Pravigard PAC is one aspirin tablet with one Pravachol tablet once a day. Pravigard PAC is available in cartons containing 30 buffered aspirin (either 81 mg or 325 mg) tablets packed with 30 Pravachol (either 20 mg, 40 mg, or 80 mg) tablets.