Data Demonstrates Continued Benefit from
Neratinib after 5 years
Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical
company, announced the presentation of positive results from the
Phase III clinical trial of Puma's drug neratinib for the extended
adjuvant treatment of early stage HER2-positive breast cancer
following trastuzumab-based therapy (ExteNET trial) in a proffered
paper oral session at the European Society of Medical Oncology
(ESMO) 2017 Congress in Madrid, Spain. 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 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.
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 presented 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
recurrent disease, ductal carcinoma in situ (DCIS), or death for a
period of five years after randomization in the trial.
The patient characteristics in the trial were well balanced
between the neratinib and placebo arms of the trial. For the 1,420
patients in the neratinib arm of the trial, 1,085 (76.4%) were node
positive while of the 1,420 patients in the placebo arm of the
trial, 1,084 (76.3%) were node positive. Additionally, in the
neratinib arm of the trial, 816 patients (57.5%) were hormone
receptor positive, and in the placebo arm of the trial, 815
patients (57.4%) were hormone receptor positive. The median time
from the last trastuzumab dose to entry into the trial was 4.4
months for the neratinib-treated patients and 4.6 months for the
placebo-treated patients.
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).
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).
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.
“While the use of trastuzumab in the adjuvant setting has led to
a reduction in the risk of disease recurrence in patients with
early stage HER2-positive breast cancer, there continues to remain
a need for further reductions in the risk of disease recurrence,”
said Professor Miguel Martin, Instituto de Investigación Sanitaria
Gregorio Marañón, CIBERONC, GEICAM, Universidad Complutense in
Madrid, Spain. “The longer term follow up results of the ExteNET
study demonstrate that we may be able to provide this type of
improvement with neratinib to further help the patients with this
disease.”
“We are very pleased with the results of the 5-year follow up
for the ExteNET trial with neratinib. This 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,” said Alan H. Auerbach, Chief
Executive Officer and President of Puma.”
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 June 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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version on businesswire.com: http://www.businesswire.com/news/home/20170908005162/en/
Puma Biotechnology, Inc.Alan H. Auerbach or Mariann Ohanesian,
+1-424-248-6500info@pumabiotechnology.comir@pumabiotechnology.comorRusso
PartnersDavid Schull or Amiad Finkelthal,
+1-212-845-4200david.schull@russopartnersllc.comamiad.finkelthal@russopartnersllc.com
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