November 14, 2014
By Riley McDermid, BioSpace.com Breaking News Editor
Development stage biopharma Puma Biotechnology, Inc . is on the ropes Friday, after announcing its only drug, cancer therapy neratinib, has failed its Phase II trial for the treatment of first-line HER2-positive locally recurrent or metastatic breast cancer.
The news sent shares of Puma down more than 14 percent as of mid-morning trading today. Puma bought the rights to develop neratinib from Pfizer Inc. in 2011.
The company had been testing the drug in a NEfERTT trial, which was a randomized, two-arm Phase II trial of neratinib plus the anticancer drug paclitaxel versus trastuzumab (Herceptin) plus paclitaxel as a first-line treatment for HER2- positive locally recurrent or metastatic breast cancer.
The study had 479 patients in 33 countries with locally recurrent or metastatic breast cancer who had not received prior anticancer therapy for locally recurrent or metastatic disease. Patients were randomized to receive first-line treatment with either paclitaxel plus neratinib or paclitaxel plus trastuzumab.
But despite promising results in July, when neratinib was found effective in improving disease-free survival of breast-cancer patients, it could not duplicate those results in the mid-stage study. Puma said it will keep trying, however, and is testing the drug in eight other studies as a treatment for various forms of cancer.
Puma was attempting to stay positive about the results in a statement released Friday morning, stressing the drug still showed promise for other types of usage.
“As expected, there was no statistically significant difference in progression free survival and objective response rate for the paclitaxel plus neratinib arm compared to the paclitaxel plus trastuzumab arm,” said Alan Auerbach, chief executive officer and president. “However, the paclitaxel plus neratinib arm showed a statistically significant decrease in the incidence of CNS metastases compared to the paclitaxel plus trastuzumab arm.”
The primary endpoint of the NEfERTT trial was progression free survival, but results did not demonstrate a statistically significant difference between the PFS and ORR results for the two treatment arms. The progression free survival for the patients who received the combination of paclitaxel plus neratinib was 16.6 months, and 16.7 month for the patients who received the combination of paclitaxel plus trastuzumab. The objective response rate in the trial for the patients who received the combination of paclitaxel plus neratinib was 74.8 percent and the objective response rate for the patients who received the combination of paclitaxel plus trastuzumab was 75.1 percent.
Puma said those results were in line with expectations and did not mean neratinib was dead in the water quite yet.
“This represents the first randomized trial with a HER2 targeted agent that has shown a statistically significant reduction in the incidence of CNS metastases, which we believe provides a meaningful point of differentiation for neratinib in the treatment of HER2 positive breast cancer,” said Auerbach. “While the development of other HER2 targeted drugs has produced a clinically meaningful benefit to patients with HER2 positive breast cancer, these drugs have had little impact on CNS metastases. As a result, we believe that there remains an unmet clinical need for reducing the incidence of CNS metastases and the results of the NEfERTT study demonstrate that we may be able to provide this type of improvement with neratinib.”
