The U.S. Food and Drug Administration (FDA) has granted accelerated approval to ceritinib (Zykadia) for patients with a metastatic anaplastic lymphoma kinase (ALK)-positive non–small cell lung cancer (NSCLC) who were previously treated with crizotinib (Xalkori). Ceritinib is an ALK tyrosine kinase inhibitor that works by blocking proteins that promote the development of cancerous cells.
Ceritinib is the fourth drug with breakthrough therapy designation to receive FDA approval. It is being approved 4 months ahead of the product’s prescription drug user fee goal date of August 24, 2014, when the agency was scheduled to complete review of the drug application.
The FDA granted ceritinib breakthrough therapy designation, priority review, and orphan product designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies; the drug had the potential, at the time of the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and the drug is intended to treat a rare disease, respectively.
Safety and Efficacy
Ceritinib’s safety and efficacy established in a clinical trial of 163 participants with metastatic ALK-positive NSCLC who had shown disease progression or were intolerant to crizotinib. All participants received ceritinib at a dose of 750 mg once daily. The primary endpoint supporting approval was objective response rate according to RECIST version 1.0, as evaluated by both investigator and blinded independent central review committee (BIRC). Duration of response was also assessed.
The trial results demonstrated durable responses of large magnitude with an overall response rate of 44% (95 confidence interval [CI] = 36–52) and duration of response of 7.1 months based on BIRC-determined tumor assessments.
The analysis by investigator assessment showed similar results, with an overall response rate of 55% (95% CI = 47–62) and duration of response of 7.4 months.
Common side effects of ceritinib include gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Laboratory abnormalities such as increased liver enzymes, pancreatic enzymes, and increased glucose levels were also observed. ■