Bayer's Stivarga® (regorafenib) Tablets Approved by U.S. FDA for Treatment of
Metastatic Colorectal Cancer
WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., Sept. 27, 2012
WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., Sept. 27, 2012 /PRNewswire/ --
Intended for U.S. Media Only --Bayer HealthCare and Onyx Pharmaceuticals,
Inc. (NASDAQ: ONXX) announced today that the U.S. Food and Drug Administration
(FDA) approved Bayer's Stivarga^® (regorafenib) tablets for the treatment of
patients with metastatic colorectal cancer (mCRC) who have been previously
treated with currently available therapies (including fluoropyrimidine-,
oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if
KRAS wild type, an anti-EGFR therapy).^1 The approval of Stivarga is based on
results from the pivotal Phase III study (CORRECT) that demonstrated
improvement in overall survival (OS) and progression-free survival (PFS)
compared to placebo in patients with mCRC whose disease had progressed after
approved standard therapies.^2,3
Stivargais a Bayer compound developed by Bayer. In 2011, Bayer entered into
an agreement with Onyx Pharmaceuticals, Inc. under which Onyx will receive
aroyalty on any future global net sales of Stivarga in oncology. Bayer and
Onyx will jointly promote Stivarga in the United States.
To view the Multimedia News Release, go to:
"The approval of regorafenib adds to the treatments we have for metastatic
colorectal cancer, which is important for those patients who have no further
options," said Heinz-Josef Lenz, MD, FACP, CORRECT investigator and associate
director for clinical research and co-leader of the Gastrointestinal Cancers
Program at the USC Norris Comprehensive Cancer Center. "The drug has been
shown to prolong survival and slow the progression of cancer in patients whose
disease has progressed after treatment with currently available therapies. It
provides patients another avenue to fight this cancer."
In the CORRECT (Colorectal cancer treated with regorafenib or placebo after
failure of standard therapy) trial, Stivarga plus best supportive care (BSC)
significantly improved OS [HR=0.77 (95% CI, 0.64-0.94), two-sided p=0.0102]
and PFS [HR=0.49 (95% CI, 0.42-0.58), two-sided p<0.0001] compared to placebo
plus BSC. ^ Median OS was 6.4 months with Stivarga versus 5.0 months with
placebo; median PFS was 2.0 months with Stivarga versus 1.7 months with
placebo. No difference in overall response rate was observed. Five patients
(1%) in the regorafenib arm and one patient (0.4%) in the placebo arm
experienced partial responses.^1
The most frequently observed adverse drug reactions (≥30%) in patients
receiving Stivarga were asthenia/fatigue, decreased appetite and food intake,
hand-foot-skin reaction (HFSR)/palmar-plantar erythrodysesthesia (PPE),
diarrhea, mucositis, weight loss, infection, hypertension and dysphonia. The
most serious adverse drug reactions in patients receiving Stivarga included
hepatotoxicity, hemorrhage, and gastrointestinal perforation. Full results
from the study were presented at the 2012 Gastrointestinal Cancers Symposium
of the American Society of Clinical Oncology (ASCO) (January 2012), and
updated results at the 48th ASCO Annual Meeting (June 2012).^2,3
"The approval of Stivarga reflects Bayer's commitment to confronting the
challenges of difficult-to-treat cancers," said Pamela A. Cyrus, MD, Vice
President and Head of U.S. Medical Affairs, Bayer HealthCare Pharmaceuticals.
"Patients with metastatic colorectal cancer whose disease has returned after
treatment will now have a new option that has been shown to prolong survival
and keep the cancer from progressing."
About Colorectal Cancer
Colorectal cancer is the third most commonly diagnosed cancer and the third
leading cause of cancer death in the United States, in both men and women. ^
It is estimated that more than 143,000 people will be diagnosed with CRC in
2012, and nearly 52,000 people will die from the disease.^4Approximately 50%
of colon cancer patients will be diagnosed with metastases (most commonly to
the liver) either at the time of diagnosis or due to recurrent disease.^5
In mCRC, KRAS status is an important biomarker and can be a predictor of
treatment response.^6 Approximately 40% of colorectal cancers are
characterized by mutations in the KRAS gene.^7
About the CORRECT Study
CORRECT was an international, multicenter, randomized, double-blind,
placebo-controlled Phase III study that enrolled 760 patients with mCRC whose
disease had progressed during or within three months following last
administration of approved standard therapies. Patients were randomized to
receive regorafenib plus BSC or placebo plus BSC. Treatment cycles consisted
of 160 mg of regorafenib (or matching placebo) once daily for three weeks on /
one week off plus BSC.^1
About Stivarga (regorafenib)
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
Stivarga is an oral multi-kinase inhibitor that inhibits various kinases
within the mechanisms involved in tumor growth and progression – angiogenesis,
oncogenesis and the tumor microenvironment. In preclinical studies, Stivarga
inhibits several angiogenic VEGF receptor tyrosine kinases 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,
PDGFR, and FGFR, which individually and collectively impact upon tumor growth,
formation of a stromal microenvironment and disease progression.^1
Stivarga was developed and reviewed under the fast track program and received
priority review designation from the FDA. These designations are granted by
the FDA to expedite the development and review of drugs to treat serious
diseases and fill an unmet medical need (fast track), and given to drugs that
provide a treatment where no adequate therapy exists (priority review).
For full prescribing information, including BOXED WARNINGS, visit
www.stivarga-us.com. Bayer offerspatient assistance through the Bayer REACH^®
(Resources for Expert Assistance and Care Helpline) program. Patients may
contact the REACH Program at 1-866-639-2827 for additional information.
Important Safety Information for Stivarga (regorafenib)
WARNING: HEPATOTOXICITY: Severe and sometimes fatal hepatotoxicity has been
observed in clinical trials. Monitor hepatic function prior to and during
treatment. Interrupt and then reduce or discontinue Stivarga for
hepatotoxicity as manifested by elevated liver function tests or
hepatocellularnecrosis,depending upon severity and persistence.
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.
In clinical trials, Stivarga was associated with an increased incidence of
hemorrhage, including fatal hemorrhage. Permanently discontinue Stivarga in
patients with severe or life-threatening hemorrhage and monitor INR levels
more frequently in patients receiving warfarin.
Hand-foot skin reaction (HFSR) (also known as palmar-plantar
erythrodysesthesia [PPE]) and rash are the most frequently observed
dermatological reactions with Stivarga. Temporarily hold and then reduce or
permanently discontinue Stivarga depending on the severity and persistence of
An increased incidence of hypertension has been observed with Stivarga. 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 has been associated with an increased incidence of myocardial
ischemia and infarction. Withhold Stivarga in patients who develop new or
acute cardiac ischemia or infarction, and resume only after resolution of
acute cardiac ischemic events.
Reversible posterior leukoencephalopathy syndrome (RPLS) has been reported
with Stivarga. Confirm the diagnosis of RPLS with MRI and discontinue Stivarga
in patients who develop RPLS.
Gastrointestinal perforation and fistula have been reported in patients
treated with Stivarga. 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. The decision to resume regorafenib 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. 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
The most frequently observed adverse drug reactions (≥30%) in Stivarga-treated
patients vs placebo-treated patients, 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
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 novel targets and pathways with the potential
to transform the way that cancer is treated across tumor types and stages of
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.
Rose Talarico, +1 973 305 5302
Lori Melancon Amy Figueroa
Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals, Inc.
+1 650 266 2394 +1 650 266 2398
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.
1. STIVARGA Prescribing Information. September 2012
2. Grothey, A., et al. Results of a randomized Phase 3 trial (CORRECT) of
regorafenib plus best supportive care (BSC) versus placebo plus BSC in
patients with mCRC who have progressed after standard therapies [January 17,
2012 ASCO-GI Presscast Presentation]. 2012 Gastrointestinal Cancers Symposium;
January 19-21, 2012. San Francisco, CA.
3. Van Cutsem, E.,et al. Phase III CORRECT trial of regorafenib in
metastatic colorectal cancer (mCRC) [Presentation]. 2012 American Society of
Clinical Oncology; June 1-5, 2012. Chicago, IL.
4. American Cancer Society. Colorectal Cancer. Available at:
Accessed on August 3, 2012.
5. National Cancer Institute. Colon Cancer Treatment. Available at:
Accessed on August 3, 2012.
6. Genetics Home Reference (A Service of the U.S. National Library of
Medicine). Gene Summary on the KRAS Gene. Available at:
http://ghr.nlm.nih.gov/gene/KRAS. Accessed on May 18, 2012.
7. National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines) Colon Cancer. Version 3.2012.
SOURCE Bayer HealthCare Pharmaceuticals, Inc.
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