Pharmacyclics Gets “Refuse To File” Letter On Xcytrin
This article was originally published in The Pink Sheet Daily
Executive Summary
Company had hoped for priority review when it submitted its NDA for treatment of brain metastases from non-small cell lung cancer in December.
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Pharmacyclics will evaluate its options for Xcytrin (motexafin gadolinium) after receiving a "refuse to file" letter in response to its NDA for treatment of brain metastases in non-small cell lung cancer patients, Chief Executive Officer Richard Miller said during a Feb. 21 conference call. "We believe that the result of our brain metastases clinical studies demonstrate that Xcytrin is an active drug. A major objective of our ongoing clinical development program is to establish Xcytrin as a systemic treatment for patients with lung cancer that have failed prior chemotherapy regimens," Miller said. FDA said in the letter that the NDA was not sufficient to "permit a substantive review based on clinical studies that failed to demonstrate statistically significant differences between treatment arms in the primary endpoints," the company said. Sunnyvale, Calif.-based Pharmacyclics submitted the NDA in December after consulting with FDA over inconsistencies in data from its pivotal Phase III SMART trial. The firm submitted data from two Phase III trials, and asked the agency to consider a six-month priority review (1 (Also see "Pharmacyclics Eyes Priority Review For NSCLC Treatment" - Pink Sheet, 22 Dec, 2006.)). Pharmacyclics reported in January 2006 that its multinational Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy (SMART) trial both missed its primary endpoint of time to neurologic progression and demonstrated no significant difference in survival, the secondary endpoint. Nonetheless, the company held out hope for marketing approval based on a regional analysis that showed North American data did achieve statistical significance (2 (Also see "Pharmacyclics Plans Xcytrin NDA Based On New Data Analysis" - Pink Sheet, 9 May, 2006.)). In addition to "a significant magnitude of benefit" shown in that data, "abnormal clinical treatment patterns in Europe" and other factors weighed in the decision to file, Miller said. "High-level people at FDA [suggested] that we file based on all of the data. We took that advice to heart; we filed an NDA document that made the best arguments that we possibly could make ... using various ways to weigh the analysis, as well as a pooled analysis ... and unfortunately ... based on the letter we received yesterday, that evidence was not persuasive enough," Miller said. Pharmacyclics is currently enrolling patients in three Phase II trials of Xcytrin for second-line use in systemic treatment of patients with lung cancer, Miller said. The oncologic is being studied alone and in combination with Sanofi-Aventis' Taxotere (docetaxel) and with Lilly's Alimta (pemetrexed), the CEO said. In addition, preliminary findings from an ongoing Phase I trial indicate that the company's lead histone deacetylase (HDAC) inhibitor candidate, PCI-24781, "achieves prolonged inhibition of the target enzyme following oral administration," he said. Merck's oral HDAC inhibitor Zolinza (vorinostat) won first-in-class approval in October for treatment of cutaneous T-cell lymphoma (3 (Also see "Merck’s Zolinza Approved For Rare Skin Cancer" - Pink Sheet, 6 Oct, 2006.)). - Shirley Haley ([email protected]) |