FDA Approves Ceritinib for ALK-Positive Lung Cancer

Zosia Chustecka

April 29, 2014

A second drug that specifically targets non-small cell lung cancer (NSCLC) that is positive for the ALK gene rearrangement has been approved by the US Food and Drug Administration (FDA).

The new drug, ceritinib (Zykadia, Novartis), in indicated for patients with ALK-positive NSCLC who have previously been treated with crizotinib (Xalkori, Pfizer), the first targeted agent for this patient population.

This is an accelerated approval, and comes 4 months ahead of schedule.

ALK gene rearrangement is found in about 2% to 7% of patients with NSCLC, which makes up about 85% of all lung cancer, according to the FDA announcement.

Since its launch in 2011, crizotinib has become a standard of care in this small patient population, with data showing that it doubles progression-free survival when compared with chemotherapy.

However, some patients become resistant to crizotinib, and until now, there has been no other targeted therapy to offer these patients. Ceritinib now fills that role.

"Ceritinib represents an important treatment option for ALK-positive NSCLC patients who relapse after starting initial therapy with crizotinib," said lead investigator Alice Shaw, MD, PhD, from the Massachusetts General Hospital Cancer Center in Boston. "This approval will affect the way we manage and monitor patients with this type of lung cancer, as we will now be able to offer them the opportunity for continued treatment response with a new ALK inhibitor," she said in a statement.

The drug went through the FDA Accelerated Approval Program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate end point reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials, the agency said.

The accelerated approval was based on a clinical trial of 163 patients with metastatic ALK-positive NSCLC, who progressed on or were intolerant to treatment with crizotinib. The most common sites of metastases in the patient population studied were brain (60%), liver (42%), and bone (42%)

Results showed that about half of the participants had their tumors shrink, and this effect lasted an average of about 7.0 months, the agency noted. The overall response rate was 54.6% (95% confidence interval [CI], 47% - 62%), and the median duration of response was of 7.4 months (95% CI, 5.4 - 10.1), the company added in its press release.

Common adverse 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.

It was approved 4 months ahead of the product's prescription drug user fee goal date of August 24, the date the agency was scheduled to complete review of the drug application.

The FDA also granted ceritinib Breakthrough Therapy Designation, priority review, and Orphan Product Designation. The manufacturer has demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies, the agency said. It had the potential, at the time the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Also, the drug is intended to treat a rare disease, it noted.


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