On March 28, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that based on its recent meetings with the U.S. Food and Drug Administration (FDA), the Company now plans to submit its New Drug Application (NDA) for the approval of neratinib for the treatment of extended adjuvant breast cancer that has previously been treated with a trastuzumab-containing regimen in mid-2016 (Press release, Puma Biotechnology, MAR 28, 2016, View Source [SID:1234510117]).

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Puma has recently conducted a series of meetings and communications with the FDA. The purpose of these communications was to provide the FDA with the data from neratinib’s non-clinical and clinical development programs that will form the basis of the Company’s NDA for neratinib for the treatment of extended adjuvant breast cancer that has previously been treated with a trastuzumab-containing regimen. The data discussed with the FDA included preclinical data (pharmacology, toxicology, reproductive toxicity, carcinogenicity) and clinical trial data, including the data from the Phase III trial of neratinib in the extended adjuvant treatment of HER2-positive early stage breast cancer (ExteNET trial) and the Phase II trial of neratinib monotherapy in the extended adjuvant treatment of HER2-positive early stage breast cancer where patients received loperamide prophylaxis in order to prevent the neratinib-related diarrhea. Following its review of this material, the FDA requested that Puma amend the current statistical analysis plan for the ExteNET trial to incorporate the FDA’s recommendations with regard to rules for censoring the data for recurrent disease events or death.

For the primary endpoint of the ExteNET trial (Invasive Disease Free Survival), the analysis was based on all recurrent disease events and deaths occurring within 2 years and 28 days post randomization. The FDA has requested that events (disease recurrence or deaths) observed after missing 2 or more scheduled disease assessments be censored at the last available disease assessment time prior to the event occurrence. The FDA’s requested approach was a sensitivity analysis used in the ExteNET trial’s original statistical analysis plan but will now be the primary analysis approach used in the trial’s updated statistical analysis plan. In order to accommodate this change, Puma expects to delay filing its NDA for neratinib for the treatment of extended adjuvant breast cancer that has previously been treated with a trastuzumab-containing regimen until mid-2016.

The primary analysis results of the trial do not appear to be altered materially by the updated analysis approach. Provided below are the results of the original and updated analyses of the primary endpoint of invasive disease-free survival (iDFS) for the intent to treat (ITT) population:

1. ITT population applying the original event and censoring rule:
– 179 iDFS events
– 33% reduction in risk of iDFS vs. placebo (hazard ratio=0.67 (0.50, 0.91), 1-sided P=0.005)
– iDFS rates 93.9% (neratinib arm) vs. 91.6% (placebo arm)

2. ITT population applying the revised event and censoring rule per FDA:
– 173 iDFS events
– 34% reduction in risk of iDFS vs. placebo (hazard ratio=0.66 (0.49, 0.90), 1-sided P=0.004)
– iDFS rates 94.2% (neratinib arm) vs. 91.9% (placebo arm)