Bayer HealthCare, a subsidiary of Bayer AG, has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for the oral multi-kinase inhibitor regorafenib for the treatment of metastatic and/or unresectable gastrointestinal stromal tumours (GIST) in patients whose disease has progressed despite prior treatment. Regorafenib is a Bayer compound developed by Bayer.

In 2011, Bayer entered into an agreement with Onyx Pharmaceuticals, Inc. under which Onyx will receive a royalty on any future global net sales of regorafenib in oncology. Bayer and Onyx will jointly promote regorafenib in the United States.

Regorafenib is an investigational oral multi-kinase inhibitor and is currently being investigated in clinical trials for its potential to treat patients with various tumour types. Regorafenib is not approved by the FDA, the European Medicines Agency (EMA) or other health authorities.

"The submission of regorafenib for the treatment of GIST marks an important milestone for Bayer, bringing us one step closer to potentially addressing a significant medical need for patients with this rare but aggressive disease," said Pamela A Cyrus, MD, vice president and Head of US Medical Affairs, Bayer HealthCare Pharmaceuticals. "With the development of regorafenib and other oncology compounds, we remain committed to discovering and advancing cancer therapies for patients who are in need of new treatment options."

The submission is based on data from the pivotal phase III GRID (GIST Regorafenib In Progressive Disease) trial, which showed that regorafenib plus best supportive care (BSC) 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 metastatic and/or unresectable GIST who were previously treated with imatinib and sunitinib. The median PFS was 4.8 months in the regorafenib arm versus 0.9 months in the placebo arm and there was a positive trend in the regorafenib group in improving overall survival (OS) [HR=0.77 (95% CI 0.42-1.41), p=0.20]. In addition, the study design allowed patients receiving placebo to cross-over following disease progression.

In this study, the most frequently reported drug-related adverse events (greater than or equal to 25 per cent) in regorafenib-treated patients versus placebo-treated patients, respectively, were hand-foot skin reaction (56.1 per cent vs.13.6 per cent), hypertension (48.5 per cent vs. 16.7 per cent), diarrhea (40.2 per cent vs.4.5 per cent), fatigue (38.6 per cent vs. 27.3 per cent) and oral mucositis (37.9 per cent vs. 7.6 per cent). Results from the study were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in June 2012.

In addition, the FDA recently agreed that Bayer can proceed with its expanded access programme (EAP) to provide regorafenib to patients diagnosed with GIST through qualified clinical sites participating in the EAP.

GRID was a randomized, double-blind, placebo-controlled, multi-centre, 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 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. The primary endpoint was progression-free survival, and secondary endpoints included overall survival, time to progression, disease control rate, tumor response rate, and duration of response. The safety and tolerability of the two treatment groups were also compared.

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.