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

• 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.

Emily Hanft, Bayer
416-240-5466
[email protected]

Ethan Pigott, beSPEAK Communications
416-558-2783
[email protected]