Bayer and Onyx Pharmaceuticals Announce Submission of FDA and EMA Applications for Nexavar® (sorafenib) for the Treatment of

Bayer and Onyx Pharmaceuticals Announce Submission of FDA and EMA Applications
 for Nexavar® (sorafenib) for the Treatment of Radioactive Iodine-Refractory
                        Differentiated Thyroid Cancer

PR Newswire

WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., July 1, 2013

WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., July 1, 2013 /PRNewswire/
--Bayer HealthCare and Onyx Pharmaceuticals (NASDAQ: ONXX) today announced
the submission of a supplemental New Drug Application (sNDA) to the U.S. Food
and Drug Administration (FDA) and an application for marketing authorization
to the European Medicines Agency (EMA) for the oral multi-kinase inhibitor
Nexavar^® (sorafenib) tablets for the treatment of locally advanced or
metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer.

"The filings in the U.S. and Europe for sorafenib for the potential treatment
of this type of thyroid cancer bring us closer to addressing an unmet medical
need for these patients who have limited or no treatment options," said Kemal
Malik, M.D., Member of the Bayer HealthCare Executive Committee and Head of
Global Development. "We are committed to exploring sorafenib's potential
applicability in hard-to-treat cancers."

"Based on results from clinical studies we believe sorafenib could potentially
provide a new option for the treatment of differentiated thyroid cancer that
no longer responds to radioactive iodine therapy," said Pablo J. Cagnoni,
M.D., Executive Vice President, Global Research & Development and Technical
Operations, Onyx Pharmaceuticals.

The regulatory submission is based on data from the Phase 3 DECISION (stuDy of
sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine
refractory thyrOid caNcer) trial, an international, multicenter,
placebo-controlled study. In the trial, sorafenib significantly extended
progression-free survival (PFS), the primary endpoint of the study, compared
to placebo. Results from the study were presented at the Annual Meeting of the
American Society of Clinical Oncology (ASCO) in June 2013.

DECISION Trial Design
The DECISION (stuDy of sorafEnib in loCally advanced or metastatIc patientS
with radioactive Iodine refractory thyrOid caNcer) trial was an international,
multicenter, placebo-controlled study. A total of 417 patients with locally
advanced or metastatic, RAI-refractory, differentiated thyroid cancer
(papillary, follicular, Hurthle cell and poorly differentiated) who had
received no prior chemotherapy, tyrosine kinase inhibitors, monoclonal
antibodies that target VEGF or VEGF receptor, or other targeted agents for
thyroid cancer were randomized to receive 400 mg of oral sorafenib twice daily
(207 patients) or matching placebo (210 patients). Ninety-six percent of
randomized patients had metastatic disease.

The primary endpoint of the study was progression-free survival, as defined by
Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints
included overall survival, time to progression, response rate and duration of
response. Safety and tolerability were also evaluated.

About Thyroid Cancer
Thyroid cancer has become the fastest-increasing cancer in the world in recent
years and is the sixth most common cancer in women.^1,2 There are more than
213,000 new cases of thyroid cancer annually and approximately 35,000 people
die from thyroid cancer worldwide each year.^3

Papillary, follicular, Hürthle cell and poorly differentiated types of thyroid
cancer are classified as "differentiated thyroid cancer" and account for
approximately 94 percent of all thyroid cancers.^4 While the majority of
differentiated thyroid cancers are curable, RAI-refractory locally advanced or
metastatic disease, is more difficult to treat and is associated with a lower
patient survival rate.^4,5

About Nexavar® (sorafenib) Tablets
Nexavar is approved in the U.S. for the treatment of patients with
unresectable hepatocellular carcinoma and for the treatment of patients with
advanced renal cell carcinoma. Nexavar is thought to inhibit both the tumor
cell and tumor vasculature. In in vitro studies, Nexavar has been shown to
inhibit multiple kinases thought to be involved in both cell proliferation
(growth) and angiogenesis (blood supply) – two important processes that enable
cancer growth. These kinases include Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3,

Nexavar is currently approved in more than 100 countries. Nexavar is also
being evaluated by Bayer and Onyx, international study groups, government
agencies and individual investigators in a range of cancers.

Important Safety Considerations For Nexavar® (sorafenib) Tablets
Nexavar in combination with carboplatin and paclitaxel is contraindicated in
patients with squamous cell lung cancer.

Cardiac ischemia and/or myocardial infarction may occur. Temporary or
permanent discontinuation of Nexavar should be considered in patients who
develop cardiac ischemia and/or myocardial infarction.

An increased risk of bleeding may occur following Nexavar administration. If
bleeding necessitates medical intervention, consider permanent discontinuation
of Nexavar.

Hypertension may occur early in the course of treatment. Monitor blood
pressure weekly during the first 6 weeks and periodically thereafter and
treat, if required.

Hand-foot skin reaction and rash are common and management may include topical
therapies for symptomatic relief. In cases of any severe or persistent adverse
reactions, temporary treatment interruption, dose modification, or permanent
discontinuation of Nexavar should be considered. Nexavar should be
discontinued if Stevens-Johnson Syndrome or toxic epidermal necrolysis are
suspected as these may be life threatening.

Gastrointestinal perforation was an uncommon adverse reaction and has been
reported in less than 1% of patients taking Nexavar. Discontinue Nexavar in
the event of a gastrointestinal perforation.

Patients taking concomitant warfarin should be monitored regularly for changes
in prothrombin time (PT), International Normalized Ratio (INR) or clinical
bleeding episodes.

Temporary interruption of Nexavar therapy is recommended in patients
undergoing major surgical procedures.

Nexavar in combination with gemcitabine/cisplatin is not recommended in
patients with squamous cell lung cancer. The safety and effectiveness of
Nexavar has not been established in patients with non-small cell lung cancer.

Nexavar can prolong the QT/QTc interval and increase the risk for ventricular
arrhythmias. Avoid use in patients with congenital long QT syndrome and
monitor patients with congestive heart failure, bradyarrhythmias, drugs known
to prolong the QT interval, and electrolyte abnormalities.

Drug-induced hepatitis with Nexavar may result in hepatic failure and death.
Liver function tests should be monitored regularly and in cases of increased
transaminases without alternative explanation Nexavar should be discontinued.

Nexavar may cause fetal harm when administered to a pregnant woman. Women of
childbearing potential should be advised to avoid becoming pregnant while on
Nexavar and female patients should also be advised against breastfeeding while
receiving Nexavar.

Elevations in serum lipase and reductions in serum phosphate of unknown
etiology have been associated with Nexavar.

Avoid concomitant use of strong CYP3A4 inducers, when possible, because
inducers can decrease the systemic exposure of Nexavar. Nexavar exposure
decreases when coadministered with oral neomycin. Effects of other antibiotics
on Nexavar pharmacokinetics have not been studied.

Most common adverse reactions reported for Nexavar-treated patients vs.
placebo-treated patients in unresectable HCC, respectively, were: diarrhea
(55% vs. 25%), fatigue (46% vs. 45%), abdominal pain (31% vs. 26%), weight
loss (30% vs. 10%), anorexia (29% vs. 18%), nausea (24% vs. 20%), and
hand-foot skin reaction (21% vs. 3%). Grade 3/4 adverse reactions were 45% vs.

Most common adverse reactions reported for Nexavar-treated patients vs.
placebo-treated patients in advanced RCC, respectively, were: diarrhea (43%
vs. 13%), rash/desquamation (40% vs. 16%), fatigue (37% vs. 28%), hand-foot
skin reaction (30% vs. 7%), alopecia (27% vs. 3%), and nausea (23% vs. 19%).
Grade 3/4 adverse reactions were 38% vs. 28%.

For information about Nexavar including U.S. Nexavar prescribing information,

www.nexavar-us.comor call 1.866.NEXAVAR (1.866.639.2827).

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 Onyx Pharmaceuticals is on Twitter. Sign up to follow
our Twitter feed @OnyxPharm at

Forward Looking Statements
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 Web site at 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 the progress and results of
the clinical development, safety, regulatory processes, commercialization
efforts or commercial potential of Nexavar. These statements are subject to
risks and uncertainties that could cause actual results and events to differ
materially from those anticipated, including risks related to the development
and commercialization of pharmaceutical products. Any statements contained in
this press release that are not statements of historical fact may be deemed to
be forward-looking statements. Reference should be made to Onyx's Quarterly
Report on Form 10-Q for the quarterly period ended March 31, 2013, filed with
the Securities and Exchange Commission under the heading "Risk Factors" for a
more detailed description of such factors. 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.

Nexavar^® is a registered trademark of Bayer HealthCare Pharmaceuticals Inc.

    Raghunandan Venkat and Marlon A. Guerrero, "Recent Advances in the
    Surgical Treatment of Differentiated Thyroid Cancer: A Comprehensive
 1. Review,"The Scientific World Journal, vol. 2013. Accessed April 11,
    Brown RL, de Souza JA, Cohen EEW. Thyroid Cancer: Burden of Illness and
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    World Health Organization: GLOBOCAN 2008. Cancer Incidence and Mortality
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    Accessed October 16, 2012.
    Naifa Lamki Busaidy and Maria E. Cabanillas, "Differentiated Thyroid
    Cancer: Management of Patients with Radioiodine Nonresponsive
 4. Disease,"Journal of Thyroid Research, vol. 2012. Accessed April 11,
    Lucia Brilli, Furio Pacini. Future Oncology. Targeted Therapy in
 5. Refractory Thyroid Cancer. 2011;7(5):657-668. Accessed April 22, 2013.

SOURCE Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.

Contact: Media: Rose Talarico, Bayer HealthCare Pharmaceuticals, (973)
305-5302 or Danielle Bertrand, Onyx Pharmaceuticals, Inc., (650) 266-2114;
Investors: Amy Figueroa, Onyx Pharmaceuticals, Inc., (650) 266-2398
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