FDA reviewers question effectiveness of Pfizer's kidney cancer drug candidate
Monday, December 19 2011 | Comments
Ahead of a Food and Drug Administration
advisory panel meeting, agency staff members expressed concern about the effectiveness of Pfizer Inc.
's Inlyta (axitinib), which is an oral selective inhibitor of vascular endothelial growth factor receptors 1, 2 and 3, for the treatment of patients with advanced renal cell carcinoma (RCC).
The company's New Drug Application (NDA) for Inlyta was supported by data from a single pivotal Phase III efficacy trial of 723 patients with advanced RCC that had progressed despite first-line therapy containing Pfizer's Sutent (sunitinib malate); Genentech Inc.
's Avastin (bevacizumab) plus interferon alfa; Pfizer's Torisel (temsirolimus); or cytokines.
The study participants were randomized to receive Inlyta at a starting dose of 5 mg twice daily, with continuous dosing, or Bayer HealthCare Pharmaceuticals Inc.
and Onyx Pharmaceuticals Inc.
's Nexavar (sorafenib tosylate) at a dose of 400 mg twice daily, with continuous dosing. The Inlyta dose could be increased to 10 mg twice daily in the absence of hypertension and high-grade adverse reactions.
Median progression-free survival (PFS), the main efficacy endpoint of the trial, was 6.7 months for the Inlyta-treated patients and 4.7 months for the Nexavar-treated patients.
However, the FDA staff noted that the PFS benefit observed with Inlyta was driven by a subset of patients who are rare in the United States. Specifically, for the patients who were treated with cytokines as a first-line systemic treatment, the difference in median PFS was 5.6 months. In contrast, the difference in median PFS was 1.4 months for the patients who had been previously treated with Sutent, and Reuters reported that patients in the United States who have kidney cancer are more likely to be given Sutent than cytokines as an initial treatment option.
The reviewers stated that Inlyta's safety profile is comparable to that of other drugs in the same class with regard to the types of adverse events that occurred during the trial. However, according to the reviewers, at the time the NDA was submitted the interim analysis for overall survival (OS) occurred at 223 events, which was slightly more than half of the events required for the final OS analysis. In that analysis, there were more deaths overall in the Inlyta treatment arm than in the Nexavar treatment arm. The final analysis for OS is anticipated in the first quarter of next year.
During a meeting slated for Dec. 7, the FDA's Oncologic Drugs Advisory Committee
will discuss whether the benefit-risk ratio is favorable for Inlyta in this patient population as a second-line therapy.
In its own premeeting documents, Pfizer said the trial data indicate that Inlyta has demonstrated a statistically significant and clinically meaningful improvement in efficacy parameters (PFS and objective response rate) when compared with Nexavar, and the drug has a favorable risk-benefit profile.
The FDA accepted Pfizer's NDA for axitinib late in June, and the agency is expected to make a decision regarding approval of the drug in early March.