Date: 2012-05-24
Type of information: Granting of a Market Authorisation in the EU
Product name: Stivarga®
Compound: regorafenib
Therapeutic area: Cancer - Oncology
Action mechanism: multi-kinase inhibitor. Stivarga® (regorafenib) 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). In addition to VEGFR 1-3 it also inhibits various oncogenic and tumor microenvironment kinases including TIE-2, RAF-1, BRAF, BRAFV600, KIT, RET, PDGFR, and FGFR, which individually and collectively impact upon tumor growth, formation of a stromal microenvironment and disease progression.
Company: Bayer Healthcare (Germany)
Disease: 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).
Latest news:
- • On August 30, 2013, Bayer HealthCare has announced that the European Commission has approved Stivarga® (regorafenib) tablets for the treatment of adult patients with metastatic colorectal cancer who have previously been treated with, or are not considered candidates for, available therapies. These include fluoropyrimidine based chemotherapy, an anti VEGF therapy and an anti EGFR therapy.
• On 27 June 2013, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the granting of a marketing authorisation for Stivarga® 40 mg film-coated tablet intended for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies. These include fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy. The benefit with Stivarga® is its ability to improve the survival of patients compared to placebo. The most common side effects are asthenia/fatigue, decreased appetite and food intake, hand foot skin reaction, diarrhoea, weight loss, infection, hypertension and dysphonia. A pharmacovigilance plan for Stivarga® will be implemented as part of the marketing authorisation.
• On March 25, 2013, Bayer HealthCare has announced that the Ministry of Health, Labor and Welfare (MHLW) in Japan has approved Stivarga® (regorafenib) tablets for the treatment of patients with unresectable, advanced/recurrent colorectal cancer (CRC). The approval is based on results from the pivotal Phase III CORRECT study that demonstrated a statistically significant improvement in overall survival and progression-free survival compared to placebo in patients with metastatic CRC (mCRC) whose disease had progressed after approved standard therapies. Full results from the CORRECT study were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June 2012 and published online in the journal The Lancet in January 2013.
• On September 27, 2012, the FDA has approved Stivarga® (regorafenib) to treat patients with colorectal cancer that has progressed after treatment and spread to other parts of the body (metastatic).
Stivarga® is being approved one month ahead of the product’s prescription drug user fee goal date of Oct. 27, 2012, the date the agency was scheduled to complete review of the drug application.
The safety and effectiveness of Stivarga® were evaluated in a single clinical study of 760 patients with previously treated metastatic colorectal cancer. Patients were randomly assigned to receive Stivarga® or placebo in addition to best supportive care (BSC), which includes treatments to help manage side effects and symptoms of cancer. Patients received treatment until their cancers progressed or side effects became unacceptable.
Study results showed patients treated with Stivarga® plus BSC lived a median of 6.4 months compared to a median of five months in patients treated with placebo plus BSC. Results also showed patients treated with Stivarga® plus BSC experienced a delay in tumor growth (progression-free survival) for a median of two months compared to a median of 1.7 months in patients receiving placebo plus BSC.
Stivarga® is being approved with a Boxed Warning alerting patients and health care professionals that severe and fatal liver toxicity occurred in patients treated with Stivarga® during clinical studies. The most common side effects reported in patients treated with Stivarga® include weakness or fatigue, loss of appetite, hand-foot syndrome (also called palmar-plantar erythrodysesthesia), diarrhea, mouth sores (mucositis), weight loss, infection, high blood pressure, and changes in voice volume or quality (dysphonia).
Regorafenib was also submitted for marketing approval 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.
Regorafenib is also under investigation in metastatic and/or unresectable gastrointestinal stromal tumors (GIST) for patients whose disease had progressed despite prior treatment with imatinib and sunitinib. Positive Phase III data showing a significant increase in PFS has been presented at the ASCO 2012 Annual Meeting. Regorafenib has been granted orphan drug designation and Fast Track designation by the FDA for this tumor type. Bayer has submitted a New Drug Application to the FDA for regorafenib in GIST in August 2012.
• On June 28, 2012, Bayer HealthCare and Onyx Pharmaceuticals have announced that the FDA has granted priority review designation to Bayer HealthCare's New Drug Application (NDA) for regorafenib, for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed after approved standard therapies.
• On May 23, 2012, Bayer HealthCare has submitted a Marketing Authorization Application to the European Medicines Agency (EMA) and a New Drug Application to the FDA for the oral multi-kinase inhibitor regorafenib for the treatment of patients with metastatic colorectal cancer (mCRC). The submissions are supported by data from the pivotal, global Phase III CORRECT (Colorectal cancer treated with regorafenib or placebo after failure of standard therapy) trial. The study evaluated regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients with mCRC whose disease has progressed after approved standard therapies. The CORRECT results showed that regorafenib plus BSC significantly improved both overall survival and progression-free survival, compared to placebo plus BSC. In this trial, the safety and tolerability of regorafenib were generally as expected and no new or unexpected toxicity was observed.
Patents:
Submission of marketing authorization application USA : 2012-05-23
Submission of marketing authorization application UE: 2012-05-23
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2012-09-27
UE authorization: 2013-08-30
Favourable opinion UE: 2013-06-27
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
