These drugs recently were approved by the FDA:
- Natalizumab (Tysabri) by Biogen Idec and Elan Pharmaceuticals. The FDA has licensed a new biologic approach to treat patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of symptom flare-ups or exacerbations of the disease. Natalizumab (Tysabri), the new product, is a monoclonal antibody bioengineered from part of a mouse antibody to closely resemble a human antibody. The product is given intravenously once a month in a physician’s office.
Although the cause of MS is unknown, it is widely considered to be an autoimmune disease in which the person’s immune system attacks the brain and/or spinal cord. Natalizumab appears to work by binding to these immune system cells, thus preventing them from traveling to the brain where they can cause damage.
Natalizumab’s approval is based on positive results seen in patients after one year of treatment.
This product received accelerated approval because it appears to provide substantial benefit for patients with a serious disease. As part of that approval, the manufacturer has committed to continuing its trials of this product for another year.
Natalizumab was evaluated for safety and efficacy in two ongoing randomized, double-blind, placebo-controlled trials in patients with relapsing forms of MS. In the first clinical trial of the product’s safety and efficacy, the drug reduced the frequency of relapses by 66% relative to placebo.
In a second trial, patients who had been treated with interferon beta-1a (Avonex), an approved treatment for MS, but who had experienced one or more relapses while on the drug, were randomized to receive natalizumab or placebo. Interferon beta-1a was continued throughout the study for both groups. In this trial, natalizumab reduced the frequency of relapses by 54% relative to placebo.
The most frequently reported serious adverse reactions were infections, including pneumonia, temporary hypersensitivity reactions (such as rash, fever, low blood pressure, and chest pain), depression, and gallstones. These serious adverse reactions were uncommon. Common adverse reactions generally were mild and included nonserious infections (such as urinary tract, lower respiratory tract, GI system, and vaginal infections), headache, depression, joint pains, and menstrual disorders.
- Erlotinib (Tarceva), manufactured by OSI Pharmaceuticals, and distributed by Genentech. The FDA has approved erlotinib (Tarceva) tablets as a single-agent treatment for patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC), the most common form of lung cancer in the United States. Erlotinib is being approved as a treatment for patients whose cancer has continued to progress despite other treatments, including at least one prior chemotherapy regimen.
Erlotinib is a drug that inhibits an enzyme, tyrosine kinase, associated with a human epidermal growth factor receptor (EGFR). The drug has shown improved survival in patients with locally advanced or metastatic NSCLC. Erlotinib received fast track status from FDA during its development.
Safety and efficacy were demonstrated in one randomized trial in 731 patients comparing erlotinib to placebo. The primary endpoint in this trial was survival. The median overall survival was 6.7 months in the erlotinib group compared with 4.7 months in the placebo group.
In about one-third of the patients, tumor cells were examined to see whether they had high or low levels of EGFR. Among the approximately 55% who had high EGFR, the effect on survival was much greater than it was in people whose EGFR levels were low. The relationship will be explored further in the future.
Common side effects reported with erlotinib in clinical trials were diarrhea, rash, nausea, and vomiting. Erlotinib may cause fetal harm when administered to pregnant women.
The FDA reviewed the application for erlotinib using the "rolling review" procedures that are available to new drug applications designated as "fast track." In rolling review, the FDA starts reviewing specific components of a drug approval application even before all the application components have been submitted to the agency. For erlotinib, the first piece of the application was submitted in January 2004, and the last portion in July 2004.