In fiscal year 2011, FDA approved 7 “new molecular entities” (NMEs) in oncology.
3. Xalkori (crizotinib) and companion genetic test for late-stage lung cancer.
Importance: 1-7% of lung cancer patients have an abnormal ALK gene. Patients with this abnormality are generally non-smokers. Xalkori was the first in a new class of drugs that targets lung cancer in these patients. This type of cancer is an orphan disease. In addition to providing a new treatment for lung cancer, Xalkori represented the second important “personalized” medicine approval of FY 2011. Xalkori was approved with a companion genetic test that will allow the drug to be targeted to the patients it is most likely to help. The genetic test, a first-of-a-kind genetic test called the Vysis ALK Break Apart FISH Probe Kit, helps determine if a patient has the abnormal ALK gene. The approval of Xalkori with a specific test allows the selection of patients who are more likely to respond to the drug. Targeted therapies such as Xalkori are important options for treating patients with this disease and may ultimately result in fewer side effects.
Actions by FDA to speed drug testing and review. In July 2011, FDA issued a draft guidance
industry on the agency’s policy for reviewing a companion diagnostic and the corresponding drug therapy. The purpose of the guidance was to help manufacturers navigate the approval process for companion drug/diagnostics more quickly and efficiently. Xalkori’s testing and review were expedited in several ways. The drug received a Fast Track designation, and was given a rolling review. Xalkori was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs. The drug was also approved under FDA’s accelerated approval program, which allowed approval of the drug based on surrogate endpoints (in this case tumor shrinkage) rather than a demonstration of improved survival. Altogether, the development time for this drug was just 5 years from first-in-human Phase 1 studies to FDA approval, a significant reduction over the average development time for cancer drugs.
Safety issues: Xalkori use has been associated with inflammation of the lung tissue (pneumonitis), which can be life-threatening. FDA concluded that the benefits of Xalkori outweighed this risk and the risk of other reported side effects. The most common side effects included vision disorders, nausea, diarrhea, vomiting, swelling (edema), and constipation. Vision disorders included visual impairment, flashes of light, blurred vision, floaters, double vision, sensitivity to light, and visual field defects.
Source: FDA - FY 2011 Innovative Drug Approvals