Pharmacyclics' NDA for Xcytrin to Be Filed Over Protest

Pharmacyclics announced it has submitted a request to the FDA asking that its new drug application (NDA) for Xcytrin injection be filed over protest.

The company had submitted an NDA to the FDA requesting approval for Xcytrin (motexafin gadolinium) in combination with radiation therapy for the treatment of brain metastases in patients with non-small-cell lung cancer (NSCLC). In February it received a refuse-to-file letter from the FDA citing failure to demonstrate statistically significant differences between treatment arms in the primary endpoint of the pivotal study.

Filing over protest is a procedure that allows a sponsor to have its NDA filed and reviewed when there is disagreement over the acceptability of the application, according to the company. Pharmacyclics said it is taking this action to ensure that its NDA receives a complete review.

"We strongly believe that the clinical data justify a complete and thorough review and that a panel of experts be given an opportunity to examine and evaluate the data," Richard Miller, president and CEO of Pharmacyclics, said.

The NDA submission was based on the results of two randomized trials and an integrated analysis of both trials. These trials used an innovative neurologic progression endpoint designed in collaboration with the FDA to assess the clinical benefit of treatment, according to the company. The first of these trials, which included 251 NSCLC patients and 150 patients with brain metastases from other solid tumors, showed a clinically and statistically significant improvement in time to neurologic progression in patients with NSCLC.

The follow up pivotal 554-patient SMART 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 in the Xcytrin arm compared with 10 months for the control arm. While not statistically significant, this represented a very strong and promising treatment effect in a disease for which nothing has worked beyond radiation therapy, the company said.