LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company,
announced top line results from the Phase III NALA trial of the
Company's lead drug candidate PB272 (neratinib) in patients with
HER2-positive metastatic breast cancer who have failed two or more prior
lines of HER2-directed treatments (third-line disease) in the setting of
metastatic disease. The Phase III NALA trial is a randomized controlled
trial of neratinib plus capecitabine versus Tykerb®
(lapatinib) plus capecitabine in patients with third-line HER2-positive
metastatic breast cancer. The trial enrolled 621 patients who were
randomized (1:1) to receive either neratinib plus capecitabine or
lapatinib plus capecitabine. The trial was conducted globally at sites
in North America, Europe, Asia-Pacific and South America. The co-primary
endpoints of the trial are centrally confirmed progression free survival
(PFS) and overall survival (OS). An alpha level of 1% was allocated to
the PFS and 4% allocated to OS. The study was to be considered positive
if either of the co-primary endpoints was positive. Puma reached
agreement with the U.S. Food and Drug Administration (FDA) under a
Special Protocol Assessment (SPA) for the design of the Phase III
clinical trial and the European Medicines Agency (EMA) also provided
follow-on scientific advice (SA) consistent with that of the FDA
regarding the Company's Phase III trial design and endpoints used in the
trial.
For the primary analysis of centrally confirmed PFS, treatment with
neratinib plus capecitabine resulted in a statistically significant
improvement in centrally confirmed PFS (p=0.0059) compared to treatment
with lapatinib plus capecitabine. For the primary analyses of OS,
neratinib plus capecitabine resulted in an improvement in OS that did
not achieve statistical significance but trended positively in favor of
the neratinib plus capecitabine arm of the study (p=0.21). For the
secondary endpoint of time to intervention for symptomatic central
nervous system disease (also referred to as brain metastases), the
results of the trial showed that treatment with neratinib plus
capecitabine led to an improvement over the combination of lapatinib
plus capecitabine (p=0.043).
The safety profile of neratinib in the Phase III NALA study was
consistent with previous clinical trials of neratinib.
Full results of the trial will be submitted to health authorities around
the world, including the U.S. Food and Drug Administration and European
Medicines Agency. Results of the trial will be submitted for
presentation at a major medical conference in 2019.
Alan H. Auerbach, Chief Executive Officer and President of Puma
Biotechnology, said, "We are highly encouraged by these results from the
NALA trial with the combination of neratinib plus capecitabine in
patients with HER2-positive metastatic breast cancer who have failed two
or more prior lines of HER2-directed treatments. We look forward to
working with the regulatory authorities in the hope of bringing another
potential treatment option to patients with HER2-positive metastatic
breast cancer as soon as possible."
Conference Call
Puma Biotechnology will host a conference call at 1:30 p.m. PST/4:30
p.m. EST on Monday, December 17, 2018, to discuss the results of its
NALA trial. The call may be accessed by dialing 1-877-709-8150
(domestic) or 1-201-689-8354 (international). Please dial in at least
ten minutes in advance and inform the operator that you would like to
join the “Puma Biotechnology Conference Call.” A live webcast of the
conference call may be accessed on the Investors section of the Puma
Biotechnology website at http://www.pumabiotechnology.com.
A replay of the call will be available approximately one hour after
completion of the call and will be archived on Puma’s website for 30
days.
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. Puma in-licenses the global development and
commercialization rights to three drug candidates — PB272 (neratinib,
oral), PB272 (neratinib, intravenous) and PB357. Neratinib, oral was
approved by the U.S. Food and Drug Administration in July 2017 for the
extended adjuvant treatment of adult patients with early stage
HER2-overexpressed/amplified breast cancer, following adjuvant
trastuzumab-based therapy, and is marketed in the United States as
NERLYNX® (neratinib) tablets. NERLYNX was granted marketing
authorization by the European Commission for the extended adjuvant
treatment of hormone receptor-positive HER2-positive early stage breast
cancer in September 2018. NERLYNX is a registered trademark of Puma
Biotechnology, Inc.
Further information about Puma Biotechnology may be found at
www.pumabiotechnology.com
.
Important Safety Information Regarding NERLYNX
®
(neratinib)
U.S. Indication
NERLYNX® (neratinib) tablets, for oral use
INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated
for the extended adjuvant treatment of adult patients with 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 inpatients
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.
To help ensure patients have access to NERLYNX, Puma has implemented the
Puma Patient Lynx support program to assist patients and health care
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.
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.
Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.
Important EU NERLYNX
®
(neratinib)
Safety Information
All suspected adverse reactions should be reported in accordance with
the national reporting system.
The adverse reactions described in this section were identified in the
randomized Phase 3 clinical trial (n=2840). The most common adverse
reactions of any grade were diarrhoea (93.6%), nausea (42.5%), fatigue
(27.3%), vomiting (26.8%), abdominal pain (22.7%), rash (15.4%),
decreased appetite (13.7%), abdominal pain upper (13.2%), stomatitis
(11.2%), and muscle spasms (10.0%).
The most common Grade 3-4 adverse reactions were diarrhoea (Grade 3,
36.9% and Grade 4, 0.2%) and vomiting (Grade 3, 3.4% and Grade 4, 0.1%).
Adverse reactions reported as serious included diarrhoea (1.9%),
vomiting (1.3%), dehydration (1.1%), nausea (0.5%), alanine
aminotransferase increased (0.4%), aspartate aminotransferase increased
(0.4%), abdominal pain (0.3%), fatigue (0.3%) and decreased appetite
(0.2%).
For full European prescribing information, please refer to the
NERLYNX (neratinib) Summary of Product Characteristics on the European
Medicines Agency website (
http://www.ema.europa.eu/ema/
).
Forward-Looking Statements
This press release contains forward-looking statements, including
statements regarding the submission of results of the NALA trial to
regulatory authorities and timing for presentation of the full results
of the NALA trial. All forward-looking statements involve risks and
uncertainties that could cause Puma’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 risk factors
disclosed in the periodic and current reports filed by Puma with the
Securities and Exchange Commission from time to time, including Puma’s
Annual Report on Form 10-K for the year ended December 31, 2017. Readers
are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof. Puma assumes no
obligation to update these forward-looking statements, except as
required by law.
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