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Publication of two pivotal Phase III studies of regorafenib: Positive Phase III Data on Bayer’s Regorafenib in Metastatic Colorectal Cancer (mCRC) and Gastrointestinal Stromal Tumor (GIST) Published in The Lancet

November 27, 2012
        --  First publication of the global Phase III CORRECT and GRID
            study data of the oral multi-kinase inhibitor regorafenib

TORONTO, Nov. 27, 2012 /CNW/ – Bayer HealthCare today announced that the
results of two pivotal Phase III studies for regorafenib were published
online in the journal The Lancet ahead of a future print publication. Data from the CORRECT (Metastatic
Colorectal cancer treated with regorafenib or placebo after failure of
standard therapy) and GRID (GIST – Regorafenib In Progressive Disease)
trials provide robust evidence for the efficacy of regorafenib in
patients with metastatic colorectal cancer (mCRC) or gastrointestinal
stromal tumor (GIST) who have exhausted all other treatment options.

“The publication of the CORRECT and GRID trials in The Lancet signifies the potential of regorafenib as a new and effective treatment
option for both mCRC and GIST, where there is a high unmet need,” said
Dr. Shurjeel Choudhri, Vice President, Medical and Scientific Affairs.
“Bayer is dedicated to developing innovative therapies to improve
patient’s lives and we will continue to expand our oncology portfolio
to make a difference for patients and physicians.”

CORRECT Trial

In the Phase III CORRECT trial regorafenib plus best supportive care
(BSC) significantly improved overall survival (OS) (HR=0.77, 1-sided
p-value=0.0052) and progression-free survival (PFS) (HR=0.49, 1-sided
p-value <0.000001) compared to placebo plus BSC in patients with mCRC
whose disease had progressed after approved standard therapies. In the
study, median OS was 6.4 months with regorafenib versus 5.0 months with
placebo; median PFS was 1.9 months with regorafenib versus 1.7 months
with placebo. The data also showed a survival benefit in the
regorafenib arm across nearly all subgroups analyzed, including no
significant difference between patients with KRAS wild-type tumor and
those with KRAS mutant tumor.  No difference in overall response rate
was observed.

“Although there has been progress in the treatment of metastatic
colorectal cancer, drug resistance remains a huge challenge,” says Dr.
Christine Cripps, Professor of Medicine University of Ottawa Cancer
Centre.  “Regorafenib is a unique oral multi-kinase inhibitor that has
the potential to become a new standard of care in mCRC and provides
hope for those patients who until now would have had no further
options.”

The most common grade 3+ adverse events (>=5% of patients) were hand-foot
skin reaction (16.6% vs. 0.4%), fatigue (15.0% vs. 8.3%), diarrhea
(8.2% vs. 2.0%), hypertension (7.6% vs. 0.8%), and rash/desquamation
(5.8% vs 0.4%). Quality of life was not adversely affected by
regorafenib. The most serious adverse drug reactions in patients
receiving regorafenib were severe liver injury, hemorrhage and
gastrointestinal perforation.

GRID Trial

The Phase III GRID trial, also published in The Lancet, showed that regorafenib plus BSC significantly improved PFS compared
to placebo plus BSC (HR=0.27, p<0.000001) in patients with metastatic
and/or unresectable GIST who were previously treated with imatinib and
sunitinib, which means a 73% reduction in the risk of progression or
death. The median PFS was 4.8 months in the regorafenib arm versus 0.9
months in the placebo arm. In addition, there was a positive trend in
the regorafenib group in improving OS (HR=0.772, p=0.199); however, the
OS did not reach statistical significance which was expected due to the
cross-over design of the trial that allowed patients receiving placebo
to receive regorafenib following disease progression.

Furthermore, a significantly greater disease control rate (DCR) was
observed with regorafenib plus BSC compared to placebo plus BSC (52.6%
vs. 9.1%; p<0.000001), DCR was defined as rate of complete response
[CR] plus partial response [PR] plus durable stable disease [SD]
maintained for at least 12 weeks. In addition, regorafenib demonstrated
therapeutic benefit independent of prior treatment options based on
analysis in pre specified subgroups that showed regorafenib had a
statistically significant PFS benefit over placebo for patients
receiving regorafenib as a third- or fourth-line treatment.

The most common grade 3 regorafenib-related adverse events which had
higher incidence (>=5% ) in the regorafenib plus BSC vs placebo plus BSC
were hypertension (27.3% vs 4.5%), hand-foot skin reaction (20.5% vs
0%), and diarrhea (7.6% vs 0%%).  Grade 4 AEs were reported at a
similar incidence in the regorafenib plus BSC vs placebo plus BSC (6.8%
vs 6.1%).

About the CORRECT Trial

The Phase III study CORRECT randomized 760 patients with mCRC whose
disease had progressed after currently approved standard therapies to
receive regorafenib plus BSC or placebo plus BSC at a 2:1 ratio.
Treatment cycles consisted of 160 mg of regorafenib (or matching
placebo) once daily for three weeks on / one week off plus BSC. The
primary endpoint of this trial was OS. Secondary endpoints included
PFS, objective tumor response rate and disease control rate. The safety
and tolerability of the two treatment groups were also compared.

About the GRID Trial

GRID was a randomized, double-blind, placebo-controlled, multi-center,
cross-over Phase III study of regorafenib for the treatment of GIST. It
randomized 199 patients whose disease had progressed despite prior
treatment with imatinib and sunitinib. Patients were randomized in a
2:1 ratio to receive either regorafenib (160 mg once daily, 3 weeks
on/1 week off) plus BSC or placebo plus BSC to evaluate efficacy and
safety. The primary endpoint of this trial was PFS, and secondary
endpoints included OS, time to progression, disease control rate, tumor
response rate, duration of response, and safety of regorafenib. 
Patients initially randomized to placebo were allowed to cross over to
open-label regorafenib once the disease progressed, of which 85% of the
patients from the placebo arm did cross over.

About Stivarga(®) (regorafenib)

Regorafenib is an oral multi-kinase inhibitor that inhibits various kinases that are
involved in mechanisms associated with tumor growth and progression
(oncogenesis),  blood vessel development (angiogenesis), and the tumor
microenvironment. In preclinical studies, Stivarga inhibits several
angiogenic VEGF receptor tyrosine kinases (VEGFR1 and murine VEGFR2/3)
that play a role in tumor neoangiogenesis (the growth of new blood
vessels). It also inhibits various oncogenic and tumor microenvironment
kinases including, KIT, RET, RAF-1, B-RAF, B-RAF(V600E), PDGFR, and FGFR1, which individually and collectively impact upon
tumor growth, formation of a stromal microenvironment and disease
progression.

Regorafenib has been submitted to Health Canada for marketing approval
for the treatment of metastatic CRC and GIST. Market authorization in
Canada has not yet been obtained.

Regorafenib was approved by the U.S. Food and Drug Administration for
the treatment of mCRC and is marketed as STIVARGA(®) and has received priority review for treatment in GIST.  Bayer has also
submitted for marketing approval of regorafenib for the treatment of
metastatic CRC in the EU in May 2012. The NDA for regorafenib for the
treatment of advanced CRC filed in Japan in July 2012 was granted
priority review.

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

About Bayer Inc.

Bayer Inc. (Bayer) is a Canadian subsidiary of Bayer AG, an
international research-based group with core businesses in health
care, crop science and innovative materials. Headquartered in Toronto,
Ontario, Bayer Inc. operates the Bayer Group’s HealthCare and
MaterialScience businesses in Canada. Bayer CropScience
Inc., headquartered in Calgary, Alberta operates as a separate legal
entity in Canada. Together, the companies play a vital role in
improving the quality of life for Canadians – producing products that
fight diseases, protecting crops and animals, and developing
high-performance materials for applications in numerous areas of daily
life. Canadian Bayer facilities include the Toronto headquarters and
offices in Montréal and Calgary.

Bayer Inc. has approximately 800 employees across Canada and had sales
of $808 million CDN in 2011. Globally, the Bayer Group had sales of
over 36 billion Euro in 2011. Bayer Inc. invested approximately $13
million CDN in research and development in 2011. Worldwide, the Bayer
Group spent the equivalent of over 2.9 billion Euro in 2011 in R&D. For
more information, go to www.bayer.ca.

Forward-Looking Statements

This 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.

SOURCE Bayer Inc.


Source: PR Newswire