Neratinib Achieves Statistically Significant Reduction in Incidence of Central Nervous System Metastases
LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a development stage
biopharmaceutical company, announced top line results from a Phase II
clinical trial of Puma's investigational drug PB272 (neratinib) for the
treatment of first-line HER2-positive locally recurrent or metastatic
breast cancer (NEfERTT trial). The NEfERTT trial is 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 NEfERTT trial enrolled 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. The primary endpoint of
the trial was progression free survival (PFS). The secondary endpoints
of the study included objective response rate (ORR) and the incidence of
central nervous system (CNS) metastases, including brain metastases.
The safety results of the study showed that the most frequently observed
adverse event for the patients who received the combination of
paclitaxel plus neratinib was diarrhea, with approximately 30% of the
patients experiencing grade 3 diarrhea. The rate of grade 3 diarrhea in
the patients who received the combination of paclitaxel plus trastuzumab
was approximately 4%. Patients who received neratinib in this trial did
not receive any prophylaxis with antidiarrheal agents to prevent the
neratinib related diarrhea. Puma’s recently reported clinical data from
a Phase II trial of neratinib in HER2 mutated non-small cell lung cancer
demonstrated that the use of high dose loperamide greatly reduces the
rate of grade 3 diarrhea with neratinib. In that trial the grade 3
diarrhea rate was 8% in the patients who received neratinib monotherapy.
In all of its current ongoing studies Puma is instituting the use of
high dose loperamide in order to continue to reduce the neratinib
related diarrhea.
The primary endpoint of the NEfERTT trial was progression free survival.
The results of the trial demonstrated that the progression free survival
for the patients who received the combination of paclitaxel plus
neratinib was 16.6 months and the progression free survival for the
patients who received the combination of paclitaxel plus trastuzumab was
16.7 months (p=0.35). The objective response rate in the trial for the
patients who received the combination of paclitaxel plus neratinib was
74.8% and the objective response rate for the patients who received the
combination of paclitaxel plus trastuzumab was 75.1% (p=0.94). These
results did not demonstrate a statistically significant difference
between the PFS and ORR results for the two treatment arms, which was
consistent with expectations.
With respect to the incidence of central nervous system metastases
(e.g., brain metastases), treatment with the combination of paclitaxel
plus neratinib resulted in a 52.6% reduction in the incidence of CNS
metastases compared to the incidence of CNS metastases in patients who
received the combination of paclitaxel plus trastuzumab. The incidence
of CNS metastases was 7.4% in the patients who received paclitaxel plus
neratinib, while the incidence of CNS metastases in the patients who
received the combination of paclitaxel plus trastuzumab was 15.6%
(p=0.006). These results reflect a statistically significant difference
between the two treatment arms.
Full results of the NEfERTT trial for PB272 will be presented at a
future scientific meeting in 2015.
“We are very pleased with the results of the NEfERTT trial with
neratinib,” said Alan H. Auerbach, Chief Executive Officer and
President. “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. However, the paclitaxel plus neratinib arm showed a
statistically significant decrease in the incidence of CNS metastases
compared to the paclitaxel plus trastuzumab arm. 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. 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.”
Conference Call and Webcast
The Company will host a conference call to discuss the NEfERTT trial
results at 2:00 p.m. PST (5:00 p.m. EST) on Thursday, November 13, 2014.
The conference call may be accessed by dialing 1-877-709-8150 for
domestic callers and 1-201-689-8354 for international callers. Please
specify to the operator that you would like to join the “Puma
Biotechnology Update Call.” The conference call will also be webcast
live and accessible through the Investor Relations section of Puma’s
website at http://www.pumabiotechnology.com/ir_events.html
and will be archived there for 30 days following the call. Please visit
Puma’s website several minutes prior to the start of the broadcast to
ensure adequate time for any software download that may be necessary.
About Puma Biotechnology
Puma Biotechnology, Inc. is a development stage biopharmaceutical
company that acquires and develops innovative products for the treatment
of various forms of cancer. The Company focuses on in-licensing drug
candidates that are undergoing or have already completed initial
clinical testing for the treatment of cancer and then seeks to further
develop those drug candidates for commercial use. The Company is
initially focused on the development of PB272 (oral neratinib), a potent
irreversible tyrosine kinase inhibitor, for the treatment of patients
with HER2-positive breast cancer and patients with non-small cell lung
cancer, breast cancer and other solid tumors that have a HER2 mutation.
Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.
Forward-Looking Statements:
This press release contains forward-looking statements, including
statements regarding anticipated timing for the presentation of data
relative to clinical trials. All forward-looking statements included in
this press release involve risks and uncertainties that could cause the
Company's actual results to differ materially from the anticipated
results and expectations expressed in these forward-looking statements.
These statements are based on current expectations, forecasts and
assumptions, and actual outcomes and results could differ materially
from these statements due to a number of factors, which include, but are
not limited to, the fact that the Company has no product revenue and no
products approved for marketing; the Company’s dependence on PB272,
which is still under development and may never receive regulatory
approval; the challenges associated with conducting and enrolling
clinical trials; the risk that the results of clinical trials may not
support the Company’s drug candidate claims; even if approved, the risk
that physicians and patients may not accept or use the Company’s
products; the Company’s reliance on third parties to conduct its
clinical trials and to formulate and manufacture its drug candidates;
the Company’s dependence on licensed intellectual property; and the
other risk factors disclosed in the periodic reports filed by the
Company with the Securities and Exchange Commission from time to time,
including the Company’s Annual Report on Form 10-K for the year
ended December 31, 2013. Readers are cautioned not to place undue
reliance on these forward-looking statements, which speak only as of the
date hereof. The Company assumes no obligation to update these
forward-looking statements, except as required by law.
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