WHIPPANY, N.J. and SOUTH SAN FRANCISCO, Calif., Aug. 30, 2013 /PRNewswire/ -- Bayer
HealthCare and Onyx Pharmaceuticals, Inc. (NASDAQ: ONXX) announced
today that the European Commission has approved Stivarga®
(regorafenib) tablets for the treatment of adult 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.
The approval of Stivarga was based on data from the pivotal
Phase III CORRECT (Colorectal cancer treated with regorafenib or
placebo after failure of standard therapy) trial. Full results from
the CORRECT study were presented at the 48th Annual
Meeting of the American Society of Clinical Oncology in
June 2012 and published online on
November 22, 2012, in The
Lancet.
About Stivarga® (regorafenib) Tablets
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 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.
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.
For full prescribing information, including BOXED WARNING, visit
www.stivarga-us.com.
Important Safety Information For Stivarga® (regorafenib)
Tablets
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
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 in mCRC (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. Perform an evaluation for RPLS in any patient presenting
with seizures, headache, visual disturbances, confusion, or altered
mental function. 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 (> or =
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 (> or =
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%).
For full prescribing information, including BOXED WARNING, visit
www.stivarga-us.com.
About Oncology at Bayer
Bayer is committed to delivering science for a better
life by advancing a portfolio of innovative treatments. The
oncology franchise at Bayer now includes three 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. Onyx
Pharmaceuticals is on Twitter. Sign up to follow our Twitter feed
@OnyxPharm at http://twitter.com/OnyxPharm.
Stivarga®, Bayer® and the Bayer Cross® are registered trademarks
of Bayer.
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 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 the progress and results of the clinical development,
safety, regulatory processes, commercialization efforts or
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 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 June 30,
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.
Intended for U.S. Media Only
SOURCE Bayer HealthCare