WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., Feb. 25, 2013 /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 to treat
patients with locally advanced, unresectable or metastatic
gastrointestinal stromal tumor (GIST) who have been previously
treated with imatinib mesylate and sunitinib malate.1
Stivarga was approved by the FDA in September 2012 for the treatment of patients with
metastatic colorectal cancer (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.1
(Photo:
http://photos.prnewswire.com/prnh/20130225/NY62678 )
"The FDA's decision marks the second approval for Stivarga –
first in metastatic colorectal cancer last year and now in locally
advanced, unresectable or metastatic GIST, where there is a high
unmet medical need for patients who have exhausted all approved
treatment options," said Pamela A.
Cyrus, MD, Vice President and Head of U.S. Medical Affairs,
Bayer HealthCare Pharmaceuticals. "These regulatory milestones
underscore Bayer's commitment to deliver effective products for
difficult-to-treat cancers."
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 in GIST is based on data from the
pivotal Phase III GRID (GIST – Regorafenib In Progressive Disease)
trial, which showed that Stivarga plus best supportive care (BSC)
statistically significantly improved progression-free survival
(PFS) compared to placebo plus BSC (HR=0.27 [95% CI 0.19-0.39],
p<0.0001) in patients with locally advanced, unresectable or
metastatic GIST who have been previously treated with imatinib
mesylate and sunitinib malate.1 The median PFS was 4.8
months in the Stivarga arm versus 0.9 months in the placebo arm
(p<0.0001). There was no statistically significant difference in
overall survival at the time of the planned interim analysis based
on 29% of the total events for the final analysis. At the time of
disease progression as assessed by central review, the study blind
was broken and all patients were offered the opportunity to take
Stivarga at the investigator's discretion. Fifty-six (85%) patients
randomized to placebo and 41 (31%) patients randomized to Stivarga
received open-label Stivarga.1
The most frequently observed adverse drug reactions (≥ 30%) in
Stivarga-treated patients vs. placebo-treated patients in GIST,
respectively, were: hand-foot skin reaction (HFSR) / palmar-plantar
erythrodysesthesia (PPE), hypertension, asthenia/fatigue, diarrhea,
mucositis, dysphonia, infection, decreased appetite and food
intake, and rash. The Stivarga label includes a boxed warning
citing the risk of hepatotoxicity. Severe and sometimes fatal
hepatotoxicity has been observed in clinical
trials.1
"While great progress has been made in the treatment of GIST
since the introduction of kinase inhibitors as effective therapies
for this orphan disease, we have been looking for additional,
effective treatments for GIST patients whose disease worsens
despite currently approved therapies," said George D. Demetri, MD, Principal Investigator of
the GRID study and Director of the Center for Sarcoma and Bone
Oncology at the Dana-Farber Cancer Institute in Boston, MA. "These data show that regorafenib
can slow disease progression in patients who are no longer
responding to other approved therapies and may provide another
avenue for GIST patients who would otherwise have no FDA-approved
treatment option."
About Gastrointestinal Stromal Tumor
(GIST)
GIST is the most common form of sarcoma (a type of cancer that
develops from certain tissues, like bone or muscle) involving the
gastrointestinal tract.2 In the United States, it is estimated that there
are approximately 4,000-5,000 new cases of GIST diagnosed each
year, of which about 1,500 have already metastasized at
diagnosis.2,3 GIST may not cause any symptoms and may be
found incidentally when the doctor is looking for other
problems.3
About the GRID Study
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 who had been
previously treated with imatinib mesylate and sunitinib malate.
Patients were randomized in a 2:1 ratio to receive either
regorafenib plus BSC or placebo plus BSC to evaluate efficacy and
safety. Treatment cycles consisted of 160 mg regorafenib (or
matching placebo) once daily for three weeks on / one week off plus
BSC. Patients continued therapy until disease progression or
unacceptable toxicity. The primary endpoint was PFS, and the key
secondary outcome measure was OS. The safety and tolerability of
the two treatment groups were also compared.4
About Stivarga (regorafenib)
Stivarga is 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.1 It is also 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.1
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
Stivarga was developed under the Fast Track program and received
priority review designations for locally advanced, unresectable or
metastatic GIST and mCRC 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 WARNING, visit
www.stivarga-us.com. Bayer offers patient 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.
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 (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 novel
targets and pathways with the potential to transform the way that
cancer is treated across tumor types and stages of disease.
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.
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 Prescribing Information,
February 2013.
2. Joensuu H. Gastrointestinal stromal
tumor (GIST). Annals of Oncology. 2006 September; Volume 17.
Available at
http://annonc.oxfordjournals.org/content/17/suppl_10/x280.full.pdf+html
. Accessed October 19, 2012.
3. American Cancer Society.
Gastrointestinal Stromal Tumor (GIST). (Last Revised 2/1/2012).
Available at
http://www.cancer.org/acs/groups/cid/documents/webcontent/003103-pdf.pdf.
Accessed October 12, 2012.
4. Casali, et al. Clinical benefit with
regorafenib across subgroups and post progression in patients with
advanced gastrointestinal stromal tumors (GIST) after progression
on imatinib (IM) and sunitinib (SU): Phase III GRID trial update.
2012 European Society of Medical Oncology; September, 2012.
Vienna, Austria.
SOURCE Bayer HealthCare Pharmaceuticals Inc.