Type of information: Granting of a Market Authorisation in the US
Product name: Stivarga®
Therapeutic area: Cancer - Oncology - Rare diseases
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: hepatocellular carcinoma
- • On April 27, 2017, the FDA expanded the approved use of Stivarga® (regorafinib) to include treatment of patients with hepatocellular carcinoma who have been previously treated with the drug sorafenib. This is the first FDA-approved treatment for a liver cancer in almost a decade.
- The safety and efficacy of Stivarga® for treatment of hepatocellular carcinoma were studied in a randomized trial of 573 patients with hepatocellular carcinoma whose tumors had progressed after receiving sorafenib (RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma trial (; NCT 01774344)] . The trial measured the overall survival, progression-free survival and the percent of patients whose tumors completely or partially shrank after treatment (overall response rate). The median overall survival for patients taking Stivarga® was 10.6 months, compared to 7.8 months for patients taking a placebo. The median progression-free survival for patients taking Stivarga® was 3.1 months compared to 1.5 months for patients taking a placebo. The overall response rate for patients taking Stivarga® was 11 percent, compared to 4 percent of patients taking placebo.Common side effects of Stivarga® include pain (including gastrointestinal and abdominal pain), hand-foot skin reaction, fatigue, diarrhea, decreased appetite, high blood pressure (hypertension), infection, difficulty speaking (dysphonia), high levels of bilirubin in the blood (hyperbilirubinemia), fever, inflammation of the mucous membranes (mucositis), weight loss, rash and nausea. Stivarga® is associated with serious risks, including liver damage (hepatotoxicity), infections, heavy bleeding (hemorrhage), holes in the stomach or intestines (gastrointestinal perforation or fistula), skin damage (dermatologic toxicity), hypertension, problems with blood flow to the heart (cardiac ischemia and infarction), temporary brain swelling(reversible posterior leukoencephalopathy syndrome) and wound healing complications.This Stivarga® application was granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.
- • On June 4, 2015, the FDA has granted orphan drug designation for Stivarga® (regorafenib) for the treatment of hepatocellular carcinoma.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-04-27
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2015-06-04
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: