Bayer's Stivarga® (regorafenib) Tablets Approved in Japan

          Bayer's Stivarga® (regorafenib) Tablets Approved in Japan

PR Newswire

WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., March 25, 2013

WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., March 25, 2013 /PRNewswire/
--Bayer HealthCare and Onyx Pharmaceuticals, Inc. (NASDAQ: ONXX) announced
today that the Ministry of Health, Labor and Welfare (MHLW) in Japan has
approved Stivarga^® (regorafenib) tablets for the treatment of patients with
metastatic colorectal cancer (mCRC).

In September 2012, Stivarga was approved by the U.S. Food and Drug
Administration (FDA) for the treatment of patients with mCRC who have been
previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based
chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR
therapy. It was approved by the U.S. FDA for the treatment of patients with
locally advanced, unresectable or metastatic gastrointestinal stromal tumor
(GIST) who have been previously treated with imatinib mesylate and sunitinib
malate in February 2013.

Stivarga is a Bayer compound developed by Bayer and jointly promoted by Bayer
and Onyx in the United States. In 2011, Bayer entered into an agreement with
Onyx, under which Onyx receives a royalty on all global net sales of Stivarga
in oncology.

The approval of Stivarga by the MHLW is based on data from the international
multicenter pivotal Phase III CORRECT (Colorectal cancer treated with
regorafenib or placebo after failure of standard therapy) trial which
evaluated regorafenib plus best supportive care (BSC) versus placebo plus BSC
in patients with mCRC, whose disease has progressed after approved standard
therapies. The CORRECT study included 20 sites in Japan.

About Stivarga (regorafenib)
In the United States, Stivarga is indicated for the treatment of patients with
mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and
irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type,
an anti-EGFR therapy. It is also indicated for the treatment of patients with
locally advanced, unresectable or metastatic gastrointestinal stromal tumor
(GIST) who have been previously treated with imatinib mesylate and sunitinib
malate.

Stivarga is an inhibitor of multiple kinases involved in normal cellular
functions and in pathologic processes such as oncogenesis, tumor angiogenesis,
and maintenance of the tumor microenvironment.^1

For full U.S. prescribing information, including BOXED WARNING, visit
www.stivarga-us.com.

Important U.S. Safety Information for Stivarga® (regorafenib) Tablets

WARNING: HEPATOTOXICITY

  oSevere and sometimes fatal hepatotoxicity has been observed in clinical
    trials.
  oMonitor hepatic function prior to and during treatment.
  oInterrupt and then reduce or discontinue STIVARGA for hepatotoxicity as
    manifested by elevated liver function tests or hepatocellular necrosis,
    depending upon severity and persistence.

Severe drug-induced liver injury with fatal outcome occurred in 0.3% of 1200
STIVARGA-treated patients across all clinical trials. In metastatic colorectal
cancer (mCRC), fatal hepatic failure occurred in 1.6% of patients in the
STIVARGA arm and in 0.4% of patients in the placebo arm; all the patients with
hepatic failure had metastatic disease in the liver. In gastrointestinal
stromal tumor (GIST), fatal hepatic failure occurred in 0.8% of patients in
the STIVARGA arm.

Obtain liver function tests (ALT, AST, and bilirubin) before initiation of
STIVARGA and monitor at least every 2 weeks during the first 2 months of
treatment. Thereafter, monitor monthly or more frequently as clinically
indicated. Monitor liver function tests weekly in patients experiencing
elevated liver function tests until improvement to less than 3 times the upper
limit of normal (ULN) or baseline values. Temporarily hold and then reduce or
permanently discontinue STIVARGA, depending on the severity and persistence of
hepatotoxicity as manifested by elevated liver function tests or
hepatocellular necrosis.

STIVARGA caused an increased incidence of hemorrhage. The overall incidence
(Grades 1-5) was 21% and 11% with STIVARGA vs 8% and 3% with placebo in mCRC
and GIST patients, respectively. Fatal hemorrhage occurred in 4 of 632 (0.6%)
STIVARGA-treated patients and involved the respiratory, gastrointestinal, or
genitourinary tracts. Permanently discontinue STIVARGA in patients with severe
or life-threatening hemorrhage and monitor INR levels more frequently in
patients receiving warfarin.

STIVARGA caused an increased incidence of hand-foot skin reaction (HFSR) (also
known as palmar-plantar erythrodysesthesia [PPE]) and severe rash, frequently
requiring dose modification. The overall incidence was 45% and 67% with
STIVARGA vs 7% and 12% with placebo in mCRC and GIST patients, respectively.
Incidence of Grade 3 HFSR (17% vs 0% in mCRC and 22% vs 0% in GIST), Grade 3
rash (6% vs <1% in mCRC and 7% vs 0% in GIST), serious adverse reactions of
erythema multiforme (0.2% vs 0% in mCRC), and Stevens-Johnson syndrome (0.2%
vs 0% in mCRC) was higher in STIVARGA-treated patients. Toxic epidermal
necrolysis occurred in 0.17% of 1200 STIVARGA-treated patients across all
clinical trials. Withhold STIVARGA, reduce the dose, or permanently
discontinue depending on the severity and persistence of dermatologic
toxicity.

STIVARGA caused an increased incidence of hypertension (30% vs 8% in mCRC and
59% vs 27% in GIST with STIVARGA vs placebo, respectively). Hypertensive
crisis occurred in 0.25% of 1200 STIVARGA-treated patients across all clinical
trials. Do not initiate STIVARGA until blood pressure is adequately
controlled. Monitor blood pressure weekly for the first 6 weeks of treatment
and then every cycle, or more frequently, as clinically indicated. Temporarily
or permanently withhold STIVARGA for severe or uncontrolled hypertension.

STIVARGA increased the incidence of myocardial ischemia and infarction (1.2%
with STIVARGA vs 0.4% with placebo). Withhold STIVARGA in patients who develop
new or acute cardiac ischemia or infarction, and resume only after resolution
of acute cardiac ischemic events if the potential benefits outweigh the risks
of further cardiac ischemia.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) occurred in 1 of 1200
STIVARGA-treated patients across all clinical trials. Confirm the diagnosis of
RPLS with MRI and discontinue STIVARGA in patients who develop RPLS.

Gastrointestinal perforation or fistula occurred in 0.6% of 1200 patients
treated with STIVARGA across clinical trials. In GIST, 2.1% (4/188) of
STIVARGA-treated patients developed gastrointestinal fistula or perforation:
of these, 2 cases of gastrointestinal perforation were fatal. Permanently
discontinue STIVARGA in patients who develop gastrointestinal perforation or
fistula.

Treatment with STIVARGA should be stopped at least 2 weeks prior to scheduled
surgery. Resuming treatment after surgery should be based on clinical judgment
of adequate wound healing. STIVARGA should be discontinued in patients with
wound dehiscence.

STIVARGA can cause fetal harm when administered to a pregnant woman. Use
effective contraception during treatment and up to 2 months after completion
of therapy. If this drug is used during pregnancy, or if the patient becomes
pregnant while taking this drug, the patient should be apprised of the
potential hazard to the fetus.

Because many drugs are excreted in human milk and because of the potential for
serious adverse reactions in nursing infants from STIVARGA, a decision should
be made whether to discontinue nursing or discontinue the drug, taking into
account the importance of the drug to the mother.

The most frequently observed adverse drug reactions (>30%) in STIVARGA-treated
patients vs placebo-treated patients in mCRC, respectively, were:
asthenia/fatigue (64% vs 46%), decreased appetite and food intake (47% vs
28%), HFSR/PPE (45% vs 7%), diarrhea (43% vs 17%), mucositis (33% vs 5%),
weight loss (32% vs 10%), infection (31% vs 17%), hypertension (30% vs 8%),
and dysphonia (30% vs 6%).

The most frequently observed adverse drug reactions (>30%) in STIVARGA-treated
patients vs placebo-treated patients in GIST, respectively, were: HFSR/PPE
(67% vs 15%), hypertension (59% vs 27%), asthenia/fatigue (52% vs 39%),
diarrhea (47% vs 9%), mucositis (40% vs 8%), dysphonia (39% vs 9%), infection
(32% vs 5%), decreased appetite and food intake (31% vs 21%), and rash (30% vs
3%).

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a
portfolio of innovative treatments.Bayer's oncology franchise now includes
two oncology products and several other compounds in various stages of
clinical development. Together, these products reflect the company's approach
to research, which prioritizes targets and pathways with the potential to
impact the way that cancer is treated.

About Bayer HealthCare Pharmaceuticals Inc.
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals
business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare
is one of the world's leading, innovative companies in the healthcare and
medical products industry, and combines the activities of the Animal Health,
Consumer Care, Medical Care, and Pharmaceuticals divisions.As a specialty
pharmaceutical company, Bayer HealthCare provides products for General
Medicine, Hematology, Neurology, Oncology and Women's Healthcare.The
company's aim is to discover and manufacture products that will improve human
health worldwide by diagnosing, preventing and treating diseases.

About Onyx Pharmaceuticals, Inc.
Based in South San Francisco, California, Onyx Pharmaceuticals, Inc. is a
global biopharmaceutical company engaged in the development and
commercialization of innovative therapies for improving the lives of people
with cancer. The company is focused on developing novel medicines that target
key molecular pathways. For more information about Onyx, visit the company's
website at www.onyx.com.

STIVARGA^® is a trademark of Bayer^®. Bayer^® and the Bayer Cross^® are
registered trademarks of Bayer.

Intended For U.S. Media Only

Forward-Looking Statement
This news release may contain forward-looking statements based on current
assumptions and forecasts made by Bayer Group or subgroup management. Various
known and unknown risks, uncertainties and other factors could lead to
material differences between the actual future results, financial situation,
development or performance of the company and the estimates given here. These
factors include those discussed in Bayer's public reports which are available
on the Bayer website at www.bayer.com. The company assumes no liability
whatsoever to update these forward-looking statements or to conform them to
future events or developments.

This news release contains "forward-looking statements" of Onyx within the
meaning of the federal securities laws. These forward-looking statements
include, without limitation, statements regarding results of clinical
development, regulatory processes, safety and commercial potential of Stivarga
(regorafenib). These statements are subject to risks and uncertainties that
could cause actual results and events to differ materially from those
anticipated, including, but not limited to, risks and uncertainties related
to: competition; failures or delays in clinical trials or the regulatory
process; Onyx or Bayer, as the case may be, may be unsuccessful in launching,
maintaining adequate supply of or obtaining reimbursement for Stivarga; market
acceptance and the rate of adoption of Stivarga; pharmaceutical pricing and
reimbursement pressures; serious adverse side effects, if they are associated
with Stivarga; and government regulation; Reference should be made to Onyx's
Annual Report on Form 10-K for the year ended December 31, 2011 filed with the
Securities and Exchange Commission, as updated by Onyx's subsequent Quarterly
Reports on Form 10-Q, under the heading "Risk Factors" for a more detailed
description of these and other risks. Readers are cautioned not to place undue
reliance on these forward-looking statements that speak only as of the date of
this release. Onyx undertakes no obligation to update publicly any
forward-looking statements to reflect new information, events, or
circumstances after the date of this release except as required by law.

References:
1. STIVARGA U.S. Prescribing Information, February 2013.

SOURCE Bayer HealthCare Pharmaceuticals Inc.

Website: http://www.bayer.com
Contact: Media, Rose Talarico, +1-973-305-5302, Email:
rose.talarico@bayer.com; Media, Danielle Bertrand, +1-650-266-2114, Investor,
Amy Figueroa, +1-650-266-2398, both of Onyx Pharmaceuticals, Inc.
 
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