FDA Accepts Pharmacyclics' NDA for Xcytrin

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Pharmacyclics announced that the FDA has accepted its new drug application (NDA) for Xcytrin. The company is seeking approval to market the drug, in combination with radiation therapy, for treating non-small-cell lung cancer (NSCLC) patients with brain metastases.

The FDA had previously refused to accept the NDA for Xcytrin (motexafin gadolinium) because a key study did not meet its primary endpoint, and Pharmacyclics had said it would file its request for review under protest. The agency has now accepted the application and set an action date under the Prescription Drug User Fee Act of Dec. 31.

"After consultation with investigators, experts and patient groups, we decided to have our NDA filed over protest because clinical evaluation of Xcytrin for the brain metastases indication required use of a novel but clinically meaningful endpoint, which should be carefully reviewed by the agency," Richard Miller, president and CEO of Pharmacyclics, said.

"Moreover, there are other examples of NDAs for oncology drugs that have been accepted for filing without meeting the primary endpoint with statistical significance," he added. "In some cases this has led to product approvals, particularly in cases where the unmet need is great, the drug is well tolerated and there are few if any other treatment options available."

The NDA is based on the results of two randomized trials and an integrated analysis of both trials. The first of these trials, which included 251 NSCLC patients and 150 patients with brain metastases from other solid tumors, did not show a statistically significant benefit overall, but it did show a clinically and statistically significant improvement in time to neurologic progression in the subset of patients with NSCLC.

A 554-patient follow-up trial showed a 5.4-month improvement in time to neurologic progression, the primary prespecified endpoint, with a median time to neurologic progression of 15.4 months for patients treated with Xcytrin compared with 10 months for the control group.