Data Demonstrates Continued Benefit from Neratinib after 5 years in Extended Adjuvant HER2-Positive Breast Cancer
LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company,
announced the publication of previously presented results from the
ExteNET Phase III clinical trial of Puma’s drug neratinib in patients
with early stage HER2-positive breast cancer in the journal The
Lancet Oncology.
The article, entitled “Neratinib after trastuzumab-based adjuvant
therapy in early stage HER2-positive breast cancer (ExteNET): 5-year
analysis of a randomized, double blind, placebo-controlled phase III
trial,” appears in the November 13th online issue of The
Lancet Oncology and will be published in a future print issue of the
journal.
The ExteNET trial is a double-blind, placebo-controlled, Phase III trial
of neratinib versus placebo after adjuvant treatment with trastuzumab
(Herceptin) in patients with early stage HER2-positive breast cancer.
The predefined 5-year invasive disease free survival (iDFS) analysis as
a follow-up to the primary 2-year iDFS analysis of the Phase III ExteNET
trial was published online today.
The ExteNET trial randomized 2,840 patients in 41 countries with early
stage HER2-positive breast cancer who had undergone surgery and adjuvant
treatment with trastuzumab. After completion of adjuvant treatment with
trastuzumab, patients were randomized to receive extended adjuvant
treatment with either neratinib or placebo for a period of one year.
Patients were then followed for invasive recurrent disease, ductal
carcinoma in situ (DCIS), or death for a period of five years after
randomization in the trial.
Neratinib was approved by the U.S. Food and Drug Administration (FDA) in
July 2017 for the extended adjuvant treatment of adult patients with
early stage HER2-positive breast cancer following adjuvant
trastuzumab-based therapy, and is marketed in the United States as
NERLYNX® (neratinib) tablets.
The primary endpoint of the trial was invasive disease free survival
(iDFS). The results of the trial demonstrated that after a median follow
up of 5.2 years, treatment with neratinib resulted in a 27% reduction of
risk of invasive disease recurrence or death versus placebo (hazard
ratio = 0.73, p = 0.008). The 5-year iDFS rate for the neratinib arm was
90.2% and the 5-year iDFS rate for the placebo arm was 87.7%.
The secondary endpoint of the trial was invasive disease free survival
including ductal carcinoma in situ (iDFS-DCIS). The results of the trial
demonstrated that treatment with neratinib resulted in a 29% reduction
of risk of disease recurrence including DCIS or death versus placebo
(hazard ratio = 0.71, p = 0.004). The 5-year iDFS-DCIS rate for the
neratinib arm was 89.7% and the 5-year iDFS-DCIS rate for the placebo
arm was 86.8%.
For the pre-defined subgroup of patients with hormone receptor positive
disease, the results of the trial demonstrated that treatment with
neratinib resulted in a 40% reduction of risk of invasive disease
recurrence or death versus placebo (hazard ratio = 0.60, p = 0.002). The
5-year iDFS rate for the neratinib arm was 91.2% and the 5-year iDFS
rate for the placebo arm was 86.8%. For the pre-defined subgroup of
patients with hormone receptor negative disease, the results of the
trial demonstrated that treatment with neratinib resulted in a hazard
ratio of 0.95 (p = 0.762).
"ExteNET represents the first trial with a HER2-targeted agent that has
shown a benefit in the extended adjuvant setting, which we believe
provides a meaningful point of differentiation for neratinib in the
treatment of HER2-positive breast cancer. We are pleased that The
Lancet Oncology has chosen to publish these results," said
Alan H. Auerbach, Chief Executive Officer and President of Puma.
The safety results were unchanged from the primary 2-year iDFS analysis
of the study that showed the most frequently observed adverse event for
the neratinib-treated patients was diarrhea, with approximately 39.9% of
the neratinib-treated patients experiencing grade 3 or higher diarrhea
(1 patient (0.1%) had grade 4 diarrhea). No evidence of increased risk
of long-term toxicity or long-term adverse consequences of
neratinib-associated diarrhea were identified in the analysis. Patients
who received neratinib in this trial did not receive any prophylaxis
with antidiarrheal agents to prevent the neratinib-related diarrhea.
Puma is currently running the ongoing CONTROL trial to investigate the
use of loperamide-based prophylaxis to reduce the incidence of grade 3
or higher diarrhea in patients with early stage HER2-positive breast
cancer who have completed adjuvant trastuzumab-based treatment. The most
recently reported clinical data from CONTROL in June 2017 demonstrated
that the use of loperamide-based prophylaxis reduced the rate of grade 3
diarrhea with neratinib, with grade 3 diarrhea rates ranging from 8-31%
when loperamide-based prophylaxis was used.
About HER2-Positive Breast Cancer
Approximately 20% to 25% of breast cancer tumors over-express the HER2
protein. HER2-positive breast cancer is often more aggressive than other
types of breast cancer, increasing the risk of disease progression and
death. Although research has shown that trastuzumab can reduce the risk
of early stage HER2-positive breast cancer returning after surgery, up
to 25% of patients treated with trastuzumab experience recurrence.
IMPORTANT SAFETY INFORMATION
NERLYNX
®
(neratinib) tablets, for oral use
INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated
for the extended adjuvant treatment of adult patients with early-stage
HER2 overexpressed/amplified breast cancer, to follow adjuvant
trastuzumab-based therapy.
CONTRAINDICATIONS: None
WARNINGS AND PRECAUTIONS:
-
Diarrhea: Aggressively manage diarrhea occurring despite
recommended prophylaxis with additional antidiarrheals, fluids, and
electrolytes as clinically indicated. Withhold NERLYNX in patients
experiencing severe and/or persistent diarrhea. Permanently
discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade
≥ 2 diarrhea that occurs after maximal dose reduction.
-
Hepatotoxicity: Monitor liver function tests monthly for the
first 3 months of treatment, then every 3 months while on treatment
and as clinically indicated. Withhold NERLYNX in patients experiencing
Grade 3 liver abnormalities and permanently discontinue NERLYNX in
patients experiencing Grade 4 liver abnormalities.
-
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise
patients of potential risk to a fetus and to use effective
contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were
diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis,
decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail
disorder, dry skin, abdominal distention, epistaxis, weight decreased
and urinary tract infection.
To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology,
Inc. at 1-844-NERLYNX (1-844-637-5969) and
www.NERLYNX.com
or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch
.
DRUG INTERACTIONS:
-
Gastric acid reducing agents: Avoid concomitant use with proton pump
inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3
hours after antacid dosing.
-
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
-
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
-
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of
narrow therapeutic agents that are P-gp substrates when used
concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:
-
Lactation: Advise women not to breastfeed.
Please see
Full
Prescribing Information
for additional safety information.
The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given
orally once daily with food, continuously for one year. Antidiarrheal
prophylaxis should be initiated with the first dose of NERLYNX and
continued during the first 2 months (56 days) of treatment and as needed
thereafter.
To help ensure patients have access to NERLYNX, Puma has implemented the
Puma Patient Lynx support program to assist patients and healthcare
providers with reimbursement support and referrals to resources that can
help with financial assistance. More information on the Puma Patient
Lynx program can be found at www.NERLYNX.com
or 1-855-816-5421.
About Puma Biotechnology
Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on
the development and commercialization of innovative products to enhance
cancer care. The Company in-licenses the global development and
commercialization rights to three drug candidates — PB272 (neratinib
(oral)), PB272 (neratinib (intravenous)) and PB357. NERLYNX®
(neratinib) is approved for commercial use by prescription in the United
States as extended adjuvant therapy for early stage HER2-positive breast
cancer following adjuvant trastuzumab-based therapy and is marketed as
NERLYNX. Neratinib is a potent irreversible tyrosine kinase inhibitor
that blocks signal transduction through the epidermal growth factor
receptors, HER1, HER2 and HER4. Currently, the Company is primarily
focused on the commercialization of NERLYNX and the continued
development of its other advanced drug candidates directed at the
treatment of HER2-positive breast cancer. The Company believes that
NERLYNX has clinical application in the potential treatment of several
other cancers that over-express or have a mutation in HER2.
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 the benefits of NERLYNX® and neratinib,
the Company’s clinical trials and the announcement of data relative to
those 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 only recently commenced
commercialization and shipment of its only FDA approved product; the
Company’s dependence upon the commercial success of NERLYNX (neratinib);
the Company’s history of operating losses and its expectation that it
will continue to incur losses for the foreseeable future; risks and
uncertainties related to the Company’s ability to achieve or sustain
profitability; the Company’s ability to predict its future prospects and
forecast its financial performance and growth; failure to obtain
sufficient capital to fund the Company’s operations; the effectiveness
of sales and marketing efforts; the Company’s ability to obtain FDA
approval or other regulatory approvals in the United States or elsewhere
for other indications for neratinib or other product candidates; 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; risks pertaining to
securities class action, derivative and defamation lawsuits; the
Company’s dependence on licensed intellectual property; and the other
risk factors disclosed in the periodic and current reports filed by the
Company with the Securities and Exchange Commission from time to time,
including the Company’s Quarterly Report on Form 10-Q for the quarter
ended September 30, 2017. 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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