Puma Biotechnology Presents Results from Phase III NALA Trial of Neratinib in Patients with HER2-Positive Metastatic Breast Cancer at the ASCO 2019 Annual Meeting

LOS ANGELES–(BUSINESS WIRE)–Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company,
announced that results from the Phase III NALA trial of 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, were
presented at the American Society of Clinical Oncology (ASCO) 2019
Annual Meeting in Chicago. “Neratinib + capecitabine versus lapatinib +
capecitabine in patients with HER2+ metastatic breast cancer previously
treated with ≥ 2 HER2-directed regimens: Findings from the
multinational, randomized, phase III NALA trial,” was presented as an
oral presentation by Adam M. Brufsky, MD, PhD, Professor of Medicine,
Co-Director, Comprehensive Breast Cancer Center, Magee Women’s Hospital
of the University of Pittsburgh Medical Center. Slides from the
presentation are available on the Puma Biotechnology website.

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 (hazard ratio=0.76, p=0.0059)
compared to treatment with lapatinib plus capecitabine. Because the
proportional hazard assumption did not hold, the statistical analysis
plan for the NALA trial prespecified that a restricted means survival
analysis at 24 months would be performed. In this prespecified analysis
the mean PFS for the patients treated with neratinib plus capecitabine
was 8.8 months and the mean PFS for the patients treated with lapatinib
plus capecitabine was 6.6 months.

For the primary analyses of OS, neratinib plus capecitabine resulted in
an improvement in OS that trended positively in favor of the neratinib
plus capecitabine arm of the study (hazard ratio = 0.88, p=0.21). The
median OS for the patients treated with neratinib plus capecitabine was
21.0 months and the median OS for the patients treated with lapatinib
plus capecitabine was 18.7 months. In the prespecified restricted means
analysis the mean OS at 48 months for the patients treated with
neratinib plus capecitabine was 24.0 months and the mean OS for the
patients treated with lapatinib plus capecitabine was 22.2 months.

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. The overall cumulative incidence of CNS metastases
was 22.8% for the neratinib plus capecitabine arm and 29.2% for the
lapatinib plus capecitabine arm (p=0.043, descriptive). For the
secondary enpoint of duration of response, neratinib plus capecitabine
treatment resulted in a longer duration of response compared to
lapatinib and capecitabine treatment, with a median response of 8.54
months compared to a median response of 5.55 months (HR = 0.495,
p = 0.0004, descriptive).

Treatment-emergent adverse events (TEAEs) were similar between arms:
TEAEs leading to neratinib/lapatinib discontinuation were lower with
neratinib (10.9%) than with lapatinib (14.5%). There was a higher rate
of grade 3 diarrhea with neratinib plus capecitabine compared to
lapatinib plus capecitabine (24.4% vs 12.5%); however, the
discontinuations due to diarrhea (neratinib plus capecitabine: 2.6%,
lapatinib plus capecitabine: 2.3%) were similar in both arms.

Puma plans to submit its New Drug Application to the U.S. Food and Drug
Administration based on the Phase III NALA trial results in the second
quarter/third quarter of 2019.

“Patients with HER2 positive metastatic breast cancer who have
progressed on two or more prior treatments continue to need additional
treatment options,” said Adam M. Brufsky, MD, PhD, Professor of
Medicine, Co-Director, Comprehensive Breast Cancer Center, Magee Women’s
Hospital of the University of Pittsburgh Medical Center. “The results of
the Phase III NALA trial are promising not only for a significant PFS
improvement and a trend toward an OS improvement, but also for the
potential to prevent progression of CNS metastases, which is a growing
concern in HER2 positive metastatic breast cancer.”

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.”

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 in September 2018 for the
extended adjuvant treatment of adult patients with early stage hormone
receptor-positive HER2-overexpressed/amplified breast cancer and who are
less than one year from completion of prior adjuvant trastuzumab-based
therapy. NERLYNX is a registered trademark of Puma Biotechnology, Inc.

Further information about Puma Biotechnology may be found at www.pumabiotechnology.com.

Forward-Looking Statements

This press release contains forward-looking statements, including
statements regarding anticipated timing for submissions with regulatory
authorities. 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 materiallyfrom 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, 2018. Readers are cautioned
not to place unduereliance 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.

Contacts

Alan H. Auerbach or Mariann Ohanesian, Puma Biotechnology, Inc.,
+1-424-248-6500
[email protected]
[email protected]

David Schull or Juliette Gorson, Russo Partners, +1-212-845-4271 /
+1-212-845-4235
[email protected]
[email protected]